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Primary Purpose
Hypersensitivity
Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Paricalcitol
Placebo (for paricalcitol)
Sponsored by
About this trial
This is an interventional diagnostic trial for Hypersensitivity
Eligibility Criteria
Inclusion Criteria (study object):
- Signed informed consent
- Age ≥18 ≤ 60 years
- Allergic rhinitis/rhino-conjunctivitis related to birch pollen with or without concomitant mild to moderate persistent asthma based on relative symptoms and allergy tests.
- A positive SPT (mean wheal diameter ≥ 3mm compared to negative control and negative control should be negative) for birch pollen assessed within 1 year before randomization OR a positive serum specific anti-birch IgE-test (>0.7 U/ml)
Inclusion Criteria (healthy control):
- Signed informed consent
- Age, gender and location matched to a study subject. An age matched control is defined as the age of the study subject ±5 years.
- No history of respiratory allergies and no nasal symptoms at screening.
- A negative SPT (a positive outcome is defined as a mean wheal diameter ≥ 3mm compared to negative control and negative control should be negative) assessed within 1 year before randomization OR a negative serum specific IgE test for aeroallergens.
Exclusion Criteria:
- A history of allergen-specific immunotherapy (SCIT or SLIT) with any allergen(s) within the 5 years before inclusion/screening visit.
- Treatment with parenteral Vitamin D3 analogue in the year before inclusion
- Significant, ongoing nasal symptoms caused by other allergens at study onset
- A history of Hypercalcemia, Hypophosphatemia or vitamin D toxicity
- Any vaccination within one week before randomization
- Treatment with experimental products within the last 3 months or during the study or biologicals (including anti-IgE or TNF- α treatment) within the last 6 months or during the study
- Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
- Uncontrolled asthma or other active respiratory diseases
- Malignancies or any malignant disease during the previous 5 years
- Severe uncontrolled diseases that could increase the risk for subjects participating in the study, including but not limited to: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or hematological disorders
- Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study
- Use of preparations containing calcium or magnesium such as thiazide, diuretics, antacides.
- Use of systemic steroids within 4 weeks before screening and during the study
- Daily use of ketoconazole cream or immunosuppressive creams at planned injection site less than 7 days before or during the study
- Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be the use of a contraceptive device or -pill)
- Any clinically significant abnormal laboratory parameter at screening
- Any physical or mental condition that precludes compliance or participation in a clinical trial
- Subjects who are employees or students of the institution or 1st grade relatives or partners of the investigators
Sites / Locations
- Academic medical center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Paricalcitol (Vitamin D3)
Placebo
Arm Description
paricalcitol, (Zemplar® 5 μg/ml Abbvie), will be administered via the subcutaneous route 4 times at 0.5 ml (registered dose of 5 μg/ml, thus 2.5 μg per sub-cutaneous injection). The minimum time interval between two injections is 4 days, which is a significantly lower frequency than the prescribed maximum of 3 times a week or every other day.
Placebo, the same constituents as Zemplar (propylene glycol 30% (v/v) alcohol 20% (v/v)) but no paricalcitol, same dosage as verum-arm.
Outcomes
Primary Outcome Measures
change in IL-10 production from baseline
Compare the change in IL-10 production as marker of the induction of a more anti-inflammatory systemic immune response, at baseline and after 4 weeks of treatment comparing birch pollen allergic subjects and healthy controls in a placebo-controlled design.
change in IL-10 production from baseline
Compare the change in IL-10 production as marker of the induction of a more anti-inflammatory systemic immune response, at baseline and at follow-up (between 5-7 weeks) comparing birch pollen allergic subjects and healthy controls in a placebo-controlled design.
Secondary Outcome Measures
Change in IgE responses to birch pollen compared to baseline
IgE responses to birch pollen measured in serum by ImmunoCAPwill be compared between subjects treated with Vitamin D3 or placebo
To evaluate the number of patients that reported adverse events with Zemplar compared to placebo. This includes adverse measurements in blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG, lung function compared to placebo.
To evaluate the number of patients that reported adverse events with the VD3 analogue Zemplar® compared to placebo. This includes adverse measurements in blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG, lung function compared to placebo.
changes in percentage Th1 cells characterized by the expression of CD4, CXCR3, CCR6 and T-bet, compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
changes in percentage Th1 cells characterized by the expression of CD4, CXCR3, CCR6 and T-bet, compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
changes in percentage Th2 cells characterized by the expression of CD4, CRTh2, CCR4 and Gata-3, compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
changes in percentage Th2 cells characterized by the expression of CD4, CRTh2, CCR4 and Gata-3, compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
changes in percentage Th17/Th22 cells characterized by the expression of CD4, CCR6, CCR4, CCR10 and RORc2 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
changes in percentage Th17/Th22 cells characterized by the expression of CD4, CCR6, CCR4, CCR10 and RORc2 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
changes in percentage Treg cells characterized by the expression of CD4, CD25, CD127, and Foxp3 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
changes in percentage Treg cells characterized by the expression of CD4, CD25, CD127, and Foxp3 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
changes in percentage B cells characterized by the expression of CD19, CD5, CD20, CD27, and CD38 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
changes in percentage B cells characterized by the expression of CD19, CD5, CD20, CD27, and CD38 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
changes in percentage antigen presenting cells characterized by the expression of CD11c, HLA-DR, CD14, CD16, CD1c, CD141, CD123, CD19, CD163, CD68, CD86 and CD83 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
changes in percentage antigen presenting cells characterized by the expression of CD11c, HLA-DR, CD14, CD16, CD1c, CD141, CD123, CD19, CD163, CD68, CD86 and CD83 compared to baseline
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Changes in the ability of PBMCs stimulated with Bet v 1, to enhance T-cell proliferation compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by allergen and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Changes in the ability of PBMCs stimulated with Bet v 1, to enhance T-cell proliferation compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by allergen and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-5 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-5 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-17 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-17 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-10 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-10 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IFN-y compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IFN-y compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce TGF-b compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with Bet v 1, to produce TGF-b compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to enhance T-cell proliferation compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to enhance T-cell proliferation compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-5 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-5 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-17 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-17 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IFN-y, compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IFN-y compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-10 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-10 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce TGF-b compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce TGF-b compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IFN-y compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IFN-y compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-4 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-4 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-9 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-9 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-13 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-17A compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-17A compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-21 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-22 compared to baseline
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02686827
Brief Title
DBPC-Dose-finding-trial of Vitamin D3 for SCIT in Birch Pollen Allergic Patients.
Acronym
BM4SIT
Official Title
A Randomized, Double-blind, Placebo-controlled Study to Determine the Immune Effects of Multiple Doses of Vitamin D3 in Patients With Allergic Rhinitis/Rhino-conjunctivitis Caused by Birch Pollen and in Healthy Control Subjects.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
October 2015 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
October 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Laurian Jongejan
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Low Vitamin D3 (VD3) levels have been reported to be associated with the risk of allergic diseases like asthma. VD3 has been demonstrated in vitro, ex vivo and in animal models to program the immune system towards anti-inflammatory immune responses. VD3 co-administered with allergen may be a promising adjuvant to improve the onset and efficacy of allergen immunotherapy (AIT). A clinical trial will be performed to compare the immune effects, the tolerability and safety of multiple doses of aVD3 analogue (registered for the intravenous route) administered by the subcutaneous (s.c.) route in subjects with allergic rhinitis and healthy controls.
The overall aim is to provide additional (in vivo) support for the use of VD3 as an adjuvant in allergen-specific immunotherapy, on top of the existing pre-clinical evidence demonstrating that antigen-presenting cells educate the adaptive immune system towards an anti-inflammatory response when allergen is seen in the presence of VD3.
Detailed Description
Low Vitamin D3 (VD3) levels have been reported to be associated with the risk of allergic diseases like asthma. In addition, VD3 has been demonstrated in vitro, ex vivo (skin-explants) and in animal models to program the immune system towards anti-inflammatory immune responses, dominated by regulatory T-cells (Treg) producing Interleukin (IL)-10. In response to allergens, healthy individuals by default have such a protective immune response against innocuous allergens, whereas allergic subjects develop an inflammatory Th2-type response. VD3 co-administered with allergen may be a promising adjuvant to improve the onset and efficacy of allergen immunotherapy (AIT), by helping the allergic immune system to divert towards an allergen-specific response dominated by regulatory T cells (Treg) and IL-10. A clinical trial will be performed to compare the immune effects, the tolerability and safety of multiple doses of a VD3 analogue (Zemplar® 5 μg/ml - Abbvie, registered for the intravenous route) administered by the subcutaneous (s.c.) route in subjects with allergic rhinitis and healthy controls. Primary and secondary outcomes will be compared at baseline and at several time points during the study to investigate whether 1) the healthy controls at baseline have a more anti-inflammatory systemic cellular immune response to polyclonal stimuli and to allergens compared to birch pollen allergic subjects, and 2) whether s.c.VD3 analogue can skew these responses in allergic subjects towards a profile more resembling the one observed in healthy controls. The overall aim is to provide additional (in vivo) support for the use of VD3 as an adjuvant in allergen-specific immunotherapy, on top of the existing pre-clinical evidence demonstrating that antigen-presenting cells educate the adaptive immune system towards an anti-inflammatory response when allergen is seen in the presence of VD3.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypersensitivity
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Paricalcitol (Vitamin D3)
Arm Type
Experimental
Arm Description
paricalcitol, (Zemplar® 5 μg/ml Abbvie), will be administered via the subcutaneous route 4 times at 0.5 ml (registered dose of 5 μg/ml, thus 2.5 μg per sub-cutaneous injection). The minimum time interval between two injections is 4 days, which is a significantly lower frequency than the prescribed maximum of 3 times a week or every other day.
Arm Title
Placebo
Arm Type
Active Comparator
Arm Description
Placebo, the same constituents as Zemplar (propylene glycol 30% (v/v) alcohol 20% (v/v)) but no paricalcitol, same dosage as verum-arm.
Intervention Type
Drug
Intervention Name(s)
Paricalcitol
Other Intervention Name(s)
Vitamin D3, (Zemplar)
Intervention Description
Vitamin D3 analogue
Intervention Type
Drug
Intervention Name(s)
Placebo (for paricalcitol)
Other Intervention Name(s)
fluid to mimic paricalcitol injection
Intervention Description
Injection fluid to mimic paricalcitol injection
Primary Outcome Measure Information:
Title
change in IL-10 production from baseline
Description
Compare the change in IL-10 production as marker of the induction of a more anti-inflammatory systemic immune response, at baseline and after 4 weeks of treatment comparing birch pollen allergic subjects and healthy controls in a placebo-controlled design.
Time Frame
baseline and 4 weeks of treatment
Title
change in IL-10 production from baseline
Description
Compare the change in IL-10 production as marker of the induction of a more anti-inflammatory systemic immune response, at baseline and at follow-up (between 5-7 weeks) comparing birch pollen allergic subjects and healthy controls in a placebo-controlled design.
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Secondary Outcome Measure Information:
Title
Change in IgE responses to birch pollen compared to baseline
Description
IgE responses to birch pollen measured in serum by ImmunoCAPwill be compared between subjects treated with Vitamin D3 or placebo
Time Frame
Baseline compared to 4 weeks of treatment
Title
To evaluate the number of patients that reported adverse events with Zemplar compared to placebo. This includes adverse measurements in blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG, lung function compared to placebo.
Description
To evaluate the number of patients that reported adverse events with the VD3 analogue Zemplar® compared to placebo. This includes adverse measurements in blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG, lung function compared to placebo.
Time Frame
Throughout the study and follow-up (a maximum total of 8 weeks)
Title
changes in percentage Th1 cells characterized by the expression of CD4, CXCR3, CCR6 and T-bet, compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
Baseline compared to 4 weeks of treatment
Title
changes in percentage Th1 cells characterized by the expression of CD4, CXCR3, CCR6 and T-bet, compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
changes in percentage Th2 cells characterized by the expression of CD4, CRTh2, CCR4 and Gata-3, compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
Baseline compared to 4 weeks of treatment
Title
changes in percentage Th2 cells characterized by the expression of CD4, CRTh2, CCR4 and Gata-3, compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
changes in percentage Th17/Th22 cells characterized by the expression of CD4, CCR6, CCR4, CCR10 and RORc2 compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
Baseline compared to 4 weeks of treatment
Title
changes in percentage Th17/Th22 cells characterized by the expression of CD4, CCR6, CCR4, CCR10 and RORc2 compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
changes in percentage Treg cells characterized by the expression of CD4, CD25, CD127, and Foxp3 compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
Baseline compared to 4 weeks of treatment
Title
changes in percentage Treg cells characterized by the expression of CD4, CD25, CD127, and Foxp3 compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
changes in percentage B cells characterized by the expression of CD19, CD5, CD20, CD27, and CD38 compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
Baseline compared to 4 weeks of treatment
Title
changes in percentage B cells characterized by the expression of CD19, CD5, CD20, CD27, and CD38 compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
changes in percentage antigen presenting cells characterized by the expression of CD11c, HLA-DR, CD14, CD16, CD1c, CD141, CD123, CD19, CD163, CD68, CD86 and CD83 compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
Baseline compared to 4 weeks of treatment
Title
changes in percentage antigen presenting cells characterized by the expression of CD11c, HLA-DR, CD14, CD16, CD1c, CD141, CD123, CD19, CD163, CD68, CD86 and CD83 compared to baseline
Description
Part of characterization of cellular composition with respect to T-cell subsets, B-cells and APCs
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to enhance T-cell proliferation compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by allergen and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to enhance T-cell proliferation compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by allergen and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-5 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-5 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-13 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-13 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-17 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-17 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-10 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-10 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-21 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-21 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-22 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IL-22 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IFN-y compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce IFN-y compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce TGF-b compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with Bet v 1, to produce TGF-b compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by Bet v 1 and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to enhance T-cell proliferation compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to enhance T-cell proliferation compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and T-cell proliferation will be measured by looking at H3-Thymidine incorporation (measured in cpm- in counts per minute)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-5 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-5 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-13 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-13 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-17 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-17 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IFN-y, compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IFN-y compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-10 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-10 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-21 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-21 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-22 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce IL-22 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce TGF-b compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated polyclonally (anti-CD3/anti-CD28), to produce TGF-b compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by (anti-CD3/anti-CD28) and cytokine production will be measured (in pg/ml)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IFN-y compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IFN-y compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-4 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-4 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-9 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-9 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-13 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-13 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-17A compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-17A compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-21 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-21 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-22 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
Baseline compared to 4 weeks of treatment
Title
Changes in the ability of PBMCs stimulated with PMA/Ionomycin, to produce IL-22 compared to baseline
Description
PBMCs from subjects treated with Vitamin D3 or placebo will be stimulated by PMA/Ionomycin and the percentage of cytokine producing cells will be measured as well as mean fluorescence intensity (MFI)
Time Frame
baseline and follow-up visit (between 5-7 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria (study object):
Signed informed consent
Age ≥18 ≤ 60 years
Allergic rhinitis/rhino-conjunctivitis related to birch pollen with or without concomitant mild to moderate persistent asthma based on relative symptoms and allergy tests.
A positive SPT (mean wheal diameter ≥ 3mm compared to negative control and negative control should be negative) for birch pollen assessed within 1 year before randomization OR a positive serum specific anti-birch IgE-test (>0.7 U/ml)
Inclusion Criteria (healthy control):
Signed informed consent
Age, gender and location matched to a study subject. An age matched control is defined as the age of the study subject ±5 years.
No history of respiratory allergies and no nasal symptoms at screening.
A negative SPT (a positive outcome is defined as a mean wheal diameter ≥ 3mm compared to negative control and negative control should be negative) assessed within 1 year before randomization OR a negative serum specific IgE test for aeroallergens.
Exclusion Criteria:
A history of allergen-specific immunotherapy (SCIT or SLIT) with any allergen(s) within the 5 years before inclusion/screening visit.
Treatment with parenteral Vitamin D3 analogue in the year before inclusion
Significant, ongoing nasal symptoms caused by other allergens at study onset
A history of Hypercalcemia, Hypophosphatemia or vitamin D toxicity
Any vaccination within one week before randomization
Treatment with experimental products within the last 3 months or during the study or biologicals (including anti-IgE or TNF- α treatment) within the last 6 months or during the study
Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
Uncontrolled asthma or other active respiratory diseases
Malignancies or any malignant disease during the previous 5 years
Severe uncontrolled diseases that could increase the risk for subjects participating in the study, including but not limited to: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or hematological disorders
Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study
Use of preparations containing calcium or magnesium such as thiazide, diuretics, antacides.
Use of systemic steroids within 4 weeks before screening and during the study
Daily use of ketoconazole cream or immunosuppressive creams at planned injection site less than 7 days before or during the study
Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be the use of a contraceptive device or -pill)
Any clinically significant abnormal laboratory parameter at screening
Any physical or mental condition that precludes compliance or participation in a clinical trial
Subjects who are employees or students of the institution or 1st grade relatives or partners of the investigators
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wytske J Fokkens, Prof MD PhD
Organizational Affiliation
Academic Medical Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Academic medical center
City
Amsterdam
ZIP/Postal Code
1100 AZ
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
The investigators have to discuss this within theEU project.
Learn more about this trial
DBPC-Dose-finding-trial of Vitamin D3 for SCIT in Birch Pollen Allergic Patients.
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