Vitamin D Supplementation in Polymorphic Light Eruption (VitD-PLE_2012)
Primary Purpose
Polymorphic Light Eruption
Status
Terminated
Phase
Phase 3
Locations
Austria
Study Type
Interventional
Intervention
Oral Vitamin D 3
Miglyol 812 N
Sponsored by
About this trial
This is an interventional prevention trial for Polymorphic Light Eruption focused on measuring Polymorphic light eruption, Vitamin D3, Photo provocation, Immune function
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of PLE by typical patient history, typical histology of skin lesions and/or positive photo provocation results
Exclusion Criteria:
- Allergy or intolerance to Oleovit D3 or Coconut/palm kernel
- Presence or history of malignant skin tumors
- Dysplastic melanocytic nevus syndrome
- Photosensitive diseases such as porphyria, chronic actinic dermatitis, xeroderma pigmentosum, and basal cell nevus syndrome; autoimmune disorders such as lupus erythematosus or dermatomyositis
- Sarcoid
- Renal dysfunction
- Psychiatric disorder
- Pregnancy or breastfeeding
- Topical treatment with vitamin D derivates within 3 months
- Oral treatment with vitamin D within 6 months
- Antinuclear antibodies such as anti-ds-DNA or anti- Ro/La
- 25-hydroxy vitamin D serum levels > 30ng/ml at screening visit
- Serum hypercalcemia > 2,65 nmol/L
- Treatment with thiazides or glycosides
- Systemic treatment with steroids and/or other immunosuppressive drugs within 4 weeks
- UV exposure in test fields within 8 weeks before the start of the study
- General poor health status
Sites / Locations
- Medical University of Graz, Department of Dermatology
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Vitamin D3
Placebo
Arm Description
Outcomes
Primary Outcome Measures
PLE test score (from 0-12) of experimental photo provocation
See study description.
Secondary Outcome Measures
Cytokine levels in serum
Chemotaxis of neutrophils
Level of regulatory T cells
Quantification of skin alterations, including cellular infiltration and cytokine profile
Dermatological quality of life (DLQI)
HADS (hospital anxiety and depression scale)
Function of regulatory T cells
Full Information
NCT ID
NCT01595893
First Posted
April 26, 2012
Last Updated
June 10, 2016
Sponsor
Medical University of Graz
Collaborators
Austrian Science Fund (FWF)
1. Study Identification
Unique Protocol Identification Number
NCT01595893
Brief Title
Vitamin D Supplementation in Polymorphic Light Eruption
Acronym
VitD-PLE_2012
Official Title
Vitamin D3 Supplementation in Polymorphic Light Eruption: Randomized Double-blinded Placebo-controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Terminated
Why Stopped
Difficulties in recruiting the planned number of patients
Study Start Date
April 2012 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of Graz
Collaborators
Austrian Science Fund (FWF)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Polymorphic light eruption (PLE) is a common photodermatosis with a high prevalence of approximately 11 to 21% in the population. Similar to lupus erythematosus (LE), an UV-inducible systemic autoimmune disease, PLE has a female preponderance with a mean onset in the second to third decade of life. PLE lesions are very itchy and typically appear on sun-exposed body sites in spring or early summer. The quality of life in patients with PLE is often severely disturbed, as evidenced by high levels of anxiety and depression. For prophylaxis besides conventional sunscreens, photo(chemo)therapy is effective in many cases, when administered over several weeks for hardening in early spring before the first natural sun exposure takes place. However, because prolonged treatment with UVB and/or photochemotherapy is potentially carcinogenic, the search for pathogenic mechanisms and new treatment options in PLE is ongoing. The exact pathogenesis of PLE is currently unknown but findings suggest an autoimmune-type background with resistance to UV-induced immune suppression and simultaneous immune reactions against skin photo-neoantigens. The investigators have recently found that PLE patients had significantly reduced 1,25-(OH)2-vitamin D3 serum levels (13-14ng/ml) compared to the normal population (>30ng/ml). In addition, the investigators were able to demonstrate in an intra-individual half-body trial that topical administration of an immunostimulatory 1,25-(OH)2-vitamin-D3 analogue calcipotriol reduced PLE symptoms in an experimental study. In the proposed randomized double-blinded placebo-controlled trial the investigators attempt to study the effect of oral vitamin D3 supplementation (2 x 40.000 IE, given orally two weeks apart) on PLE symptoms.
Detailed Description
PLE patients will be subjected to experimental photo provocation with solar simulated UV radiation over several days before and after vitamin D3 supplementation. Disease symptoms will be quantified with a newly established and validated PLE test score, (AA + SI + 0.4P [range, 0-12], where AA is affected area score [range, 0-4], SI is skin infiltration score [range, 0-4], and P is pruritus score on a visual analogue scale [range, 0-10]). Optional biopsies will be taken to investigate the effect of oral vitamin D3 on UV-induced skin test sites, including cellular skin infiltration and expression and release of cytokines in situ as endpoints. We will also study the effect of oral vitamin D3 on abnormalities i) of levels and function of regulatory T cells, ii) chemotaxis of leucocytes, and iii) proinflammatory cytokines, i.e. alterations that have been previously linked to PLE pathogenesis. This will be done by i) FACS and co-culture T cell proliferation assays, ii) response of peripheral neutrophil leucocytes to the chemoattractants leukotriene B4 (LTB4) and formyl-methionyl-leucyl-phenylalanine, and iii) ELISA and immunobead assay of patient serum.
To back-up the results obtained with the PLE test score upon experimental photo provocation the study participants will receive a questionnaire on PLE symptoms and quality of life, adapted from scores as previously described. This questionnaire will allow monitoring PLE symptoms and quality of life in the patients during the summer season following the oral vitamin D3 supplementation in spring.
The results of the project will enlighten the mechanism of PLE and may establish the base of a novel prevention strategy via the vitamin D3 pathway.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polymorphic Light Eruption
Keywords
Polymorphic light eruption, Vitamin D3, Photo provocation, Immune function
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vitamin D3
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Oral Vitamin D 3
Other Intervention Name(s)
Oleovit D3, Fresenius Kabi, Austria
Intervention Description
40,000 IE vitamin D3 per 70 kg body weight, given twice (2 weeks apart)
Intervention Type
Drug
Intervention Name(s)
Miglyol 812 N
Other Intervention Name(s)
Vegetable oil
Intervention Description
Neutral oil of esters extracted from coconut and palm kernel
Primary Outcome Measure Information:
Title
PLE test score (from 0-12) of experimental photo provocation
Description
See study description.
Time Frame
At day 2, 3, 4, 5, and 8 (change from baseline)
Secondary Outcome Measure Information:
Title
Cytokine levels in serum
Time Frame
At day 22 and 36; and at month 4-8
Title
Chemotaxis of neutrophils
Time Frame
At day 22 and 36; and at month 4-8 (compared to baseline)
Title
Level of regulatory T cells
Time Frame
At day 22 and 36; and at month 4-8 (compared to baseline)
Title
Quantification of skin alterations, including cellular infiltration and cytokine profile
Time Frame
Day 5 and 40
Title
Dermatological quality of life (DLQI)
Time Frame
At month 4-8
Title
HADS (hospital anxiety and depression scale)
Time Frame
At month 4-8
Title
Function of regulatory T cells
Time Frame
22 and 36; and at month 4-8 (compared to baseline)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed diagnosis of PLE by typical patient history, typical histology of skin lesions and/or positive photo provocation results
Exclusion Criteria:
Allergy or intolerance to Oleovit D3 or Coconut/palm kernel
Presence or history of malignant skin tumors
Dysplastic melanocytic nevus syndrome
Photosensitive diseases such as porphyria, chronic actinic dermatitis, xeroderma pigmentosum, and basal cell nevus syndrome; autoimmune disorders such as lupus erythematosus or dermatomyositis
Sarcoid
Renal dysfunction
Psychiatric disorder
Pregnancy or breastfeeding
Topical treatment with vitamin D derivates within 3 months
Oral treatment with vitamin D within 6 months
Antinuclear antibodies such as anti-ds-DNA or anti- Ro/La
25-hydroxy vitamin D serum levels > 30ng/ml at screening visit
Serum hypercalcemia > 2,65 nmol/L
Treatment with thiazides or glycosides
Systemic treatment with steroids and/or other immunosuppressive drugs within 4 weeks
UV exposure in test fields within 8 weeks before the start of the study
General poor health status
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Wolf, MD
Organizational Affiliation
Medical University of Graz
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Graz, Department of Dermatology
City
Graz
ZIP/Postal Code
A-8036
Country
Austria
12. IPD Sharing Statement
Citations:
PubMed Identifier
26911519
Citation
Schweintzger NA, Gruber-Wackernagel A, Shirsath N, Quehenberger F, Obermayer-Pietsch B, Wolf P. Influence of the season on vitamin D levels and regulatory T cells in patients with polymorphic light eruption. Photochem Photobiol Sci. 2016 Mar;15(3):440-6. doi: 10.1039/c5pp00398a. Epub 2016 Feb 25.
Results Reference
derived
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Vitamin D Supplementation in Polymorphic Light Eruption
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