Back to resultsDose-related Effects of Vitamin D3 on Immune Responses in Patients With Clinically Isolated Syndrome (CISAVID)
Primary Purpose
Clinically Isolated Syndrome, Multiple Sclerosis
Status
Completed
Phase
Phase 1
Locations
Ireland
Study Type
Interventional
Intervention
5000IU vitamin D
10000IU vitamin D
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Clinically Isolated Syndrome focused on measuring Clinically isolated syndrome, Multiple sclerosis, Vitamin D, Immune response, CD4 T cell subsets, Cytokine
Eligibility Criteria
Inclusion Criteria: To be eligible for inclusion, each subject must meet each of the following criteria at Screening (Visit 1) and must continue to fulfil these criteria at Baseline (Visit 2).
- CIS: Patients with a clinically isolated syndrome with onset relapse within the previous three months and two or more than two asymptomatic T2 lesions on MRI brain scan.
- Aged 18-55yrs.
- Not receiving any disease modifying therapy.
Exclusion Criteria:
- Patients in whom any disease other than demyelination could explain their signs and symptoms.
- Participants with known disease of the parathyroids, a history of vitamin D intolerance, sarcoidosis, a history of hypercalcaemia of any cause.
- Participants with a baseline abnormality in serum urea, creatinine, calcium, parathormone.
- Participants on thiazide diuretics (hypercalcaemia risk).
- Patients with occurrence of a relapse less than six weeks prior to entry to study.
- Previous treatment with beta-interferons or glatiramer acetate or steroids in the last three months.
- Any previous treatment with mitoxantrone or other immunosuppressant.
- Participants already taking supplemental vitamin D.
Sites / Locations
- St Vincent's University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Healthy control - 5,000 IU vitamin D
Healthy control - 10,000 IU vitamin D
CIS - placebo
CIS - 5,000 IU vitamin D
CIS - 10,000 IU vitamin D
Healthy control - placebo
Arm Description
13 healthy controls will be administered 5,000 IU vitamin D. Primary outcome and safety outcome measures will be assessed.
13 healthy controls will be administered 10,000 IU vitamin D. Primary outcome and safety outcome measures will be assessed.
15 patients will be administered placebo and all outcome measures will be assessed.
15 patients will be administered 5,000 IU vitamin D and all outcomes will be assessed.
15 patients will be administered 10,000 IU of vitamin D and all outcome measures assessed.
13 control participants who will be administered placebo. These will be assessed for the primary outcome and safety outcomes only.
Outcomes
Primary Outcome Measures
The effects of two doses of vitamin D and placebo therapy on the change in the frequency of CD4 T cell subsets and cytokine responses of PBMC over 24 weeks of therapy from baseline.
A number of measures will be examined in particular IL-10 production and the frequency of Th17 cells.
Secondary Outcome Measures
The number of new T2 and gadolinium enhancing lesions compared to baseline amongst the study group.
The MRI out-come measure will assess the a) number of Gadolinium enhancing lesions b) the number of new and enlarging T2 lesions c) the combined unique lesion count (new and enlarging T2 lesions plus Gadolinium enhancing lesions) after 24 weeks of therapy in the three arms, 5000IU, 10,000IU vitamin D and placebo . Mean and median new T2 and gadolinium-enhancing lesions at 24 weeks (end of the trial) will be compared for each treatment allocation group. In addition the mean and median number of new T2 lesions plus gadolinium enhancing lesions in all the CIS patients on vitamin D will be compared to the mean and median in the placebo group.
Relapse occurrence in the CIS patients during 24 weeks of the trial
Relapse occurrence in the CIS patients during 24 weeks of the trial;(i) annualised relapse rates (ARR), (ii) percentage of patients free from relapses and (iii) time to first relapse will be compared for each treatment allocation group. In addition the same relapse measures will be applied to both vitamin D treated groups combined and compared to those in the placebo group.
The percentage of CIS patients in each treatment arm free from any evidence of disease activity (No relapses, no new T2 lesions, no gadolinium enhancing lesions).
Full Information
NCT ID
NCT01728922
First Posted
November 8, 2012
Last Updated
May 1, 2017
Sponsor
University College Dublin
Collaborators
University of Dublin, Trinity College, St Vincent's University Hospital, Ireland
1. Study Identification
Unique Protocol Identification Number
NCT01728922
Brief Title
Dose-related Effects of Vitamin D3 on Immune Responses in Patients With Clinically Isolated Syndrome
Acronym
CISAVID
Official Title
Dose-related Effects of Vitamin D3 on Immune Responses in Patients With Clinically Isolated Syndrome and Healthy Control Participants. An Exploratory Double Blind Placebo Randomised Controlled Study.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
November 6, 2012 (Actual)
Primary Completion Date
June 5, 2015 (Actual)
Study Completion Date
June 5, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University College Dublin
Collaborators
University of Dublin, Trinity College, St Vincent's University Hospital, Ireland
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary purpose of this study is to assess the immune response to vitamin D supplementation at two doses (5,000 IU and 10,000 IU daily) in both healthy controls and patients with clinically isolated syndrome compared to placebo. Secondary endpoints include (1) disease outcome in the clinically isolated syndrome in terms of clinical relapses and evidence of new lesions on MRI (McDonald's MS), 2) Safety of doses used
Detailed Description
Primary endpoint: To determine the effects of vitamin D supplementation at two doses a) 5,000 IU daily b) 10,000 IU daily compared to c) placebo a 24 weeks period on the change from baseline in frequency of CD4 T cell subsets and cytokine responses by peripheral blood mononuclear cells in 1) patients with the clinically isolated syndrome. 2) healthy control participants.
Secondary endpoints:
To determine whether there is a dose response effect of supplementation using 5,000 IU and 10,000 IU of vitamin D versus placebo over 24 weeks on the change from baseline in the frequency of CD4 T cell subsets and cytokine responses by PBMC in 1) patients with the clinically isolated syndrome (CIS) 2) healthy control participants
To establish whether there is a clinical response to vitamin D measured by a) change in the number of T2 lesions and Gadolinium enhancing lesions on MRI scanning at 24 weeks compared to baseline b) reduction in relapses over 24 weeks in treated (both 5,000 IU and 10,000 IU) CIS patients versus CIS patients receiving placebo.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clinically Isolated Syndrome, Multiple Sclerosis
Keywords
Clinically isolated syndrome, Multiple sclerosis, Vitamin D, Immune response, CD4 T cell subsets, Cytokine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
double-blind, dose ranging, two doses of vitamin D, randomised parallel groups with placebo arms in clinically isolated syndrome and heathy control participants
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
similar appearance of placebo and active drug
Allocation
Randomized
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Healthy control - 5,000 IU vitamin D
Arm Type
Active Comparator
Arm Description
13 healthy controls will be administered 5,000 IU vitamin D. Primary outcome and safety outcome measures will be assessed.
Arm Title
Healthy control - 10,000 IU vitamin D
Arm Type
Active Comparator
Arm Description
13 healthy controls will be administered 10,000 IU vitamin D. Primary outcome and safety outcome measures will be assessed.
Arm Title
CIS - placebo
Arm Type
Placebo Comparator
Arm Description
15 patients will be administered placebo and all outcome measures will be assessed.
Arm Title
CIS - 5,000 IU vitamin D
Arm Type
Active Comparator
Arm Description
15 patients will be administered 5,000 IU vitamin D and all outcomes will be assessed.
Arm Title
CIS - 10,000 IU vitamin D
Arm Type
Active Comparator
Arm Description
15 patients will be administered 10,000 IU of vitamin D and all outcome measures assessed.
Arm Title
Healthy control - placebo
Arm Type
Placebo Comparator
Arm Description
13 control participants who will be administered placebo. These will be assessed for the primary outcome and safety outcomes only.
Intervention Type
Dietary Supplement
Intervention Name(s)
5000IU vitamin D
Other Intervention Name(s)
Vigantol Oil
Intervention Description
Vigantol Oil
Intervention Type
Dietary Supplement
Intervention Name(s)
10000IU vitamin D
Other Intervention Name(s)
Vigantol Oil
Intervention Description
Vigantol Oil
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo Oil
Intervention Description
Placebo Oil
Primary Outcome Measure Information:
Title
The effects of two doses of vitamin D and placebo therapy on the change in the frequency of CD4 T cell subsets and cytokine responses of PBMC over 24 weeks of therapy from baseline.
Description
A number of measures will be examined in particular IL-10 production and the frequency of Th17 cells.
Time Frame
This outcome measure will be assessed at baseline and at 24 weeks.
Secondary Outcome Measure Information:
Title
The number of new T2 and gadolinium enhancing lesions compared to baseline amongst the study group.
Description
The MRI out-come measure will assess the a) number of Gadolinium enhancing lesions b) the number of new and enlarging T2 lesions c) the combined unique lesion count (new and enlarging T2 lesions plus Gadolinium enhancing lesions) after 24 weeks of therapy in the three arms, 5000IU, 10,000IU vitamin D and placebo . Mean and median new T2 and gadolinium-enhancing lesions at 24 weeks (end of the trial) will be compared for each treatment allocation group. In addition the mean and median number of new T2 lesions plus gadolinium enhancing lesions in all the CIS patients on vitamin D will be compared to the mean and median in the placebo group.
Time Frame
Baseline and 24 weeks
Title
Relapse occurrence in the CIS patients during 24 weeks of the trial
Description
Relapse occurrence in the CIS patients during 24 weeks of the trial;(i) annualised relapse rates (ARR), (ii) percentage of patients free from relapses and (iii) time to first relapse will be compared for each treatment allocation group. In addition the same relapse measures will be applied to both vitamin D treated groups combined and compared to those in the placebo group.
Time Frame
At each clinic visit or as the need arises.
Title
The percentage of CIS patients in each treatment arm free from any evidence of disease activity (No relapses, no new T2 lesions, no gadolinium enhancing lesions).
Time Frame
At 24 weeks.
Other Pre-specified Outcome Measures:
Title
Serum calcium
Description
a measure of calcium homeostasis
Time Frame
Every 4 weeks for 24 weeks
Title
Number of participants with adverse events as a measure of safety and tolerability of vitamin D in doses of 5,000IU and 10,000IU daily
Time Frame
four weekly assessments over 24 weeks
Title
serum urea
Description
a measure of renal function
Time Frame
4 weekly over 24 weeks
Title
serum creatinine
Description
a measure of renal function
Time Frame
4 weekly over 24 weeks
Title
serum 25(OH)D levels
Description
a measure of response to oral dosing and adherence to therapy.
Time Frame
4 weekly over 24 weeks
Title
serum parathormone (iPTH)
Description
a measure of parathyroid function
Time Frame
4 weekly over 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: To be eligible for inclusion, each subject must meet each of the following criteria at Screening (Visit 1) and must continue to fulfil these criteria at Baseline (Visit 2).
CIS: Patients with a clinically isolated syndrome with onset relapse within the previous three months and two or more than two asymptomatic T2 lesions on MRI brain scan.
Aged 18-55yrs.
Not receiving any disease modifying therapy.
Exclusion Criteria:
Patients in whom any disease other than demyelination could explain their signs and symptoms.
Participants with known disease of the parathyroids, a history of vitamin D intolerance, sarcoidosis, a history of hypercalcaemia of any cause.
Participants with a baseline abnormality in serum urea, creatinine, calcium, parathormone.
Participants on thiazide diuretics (hypercalcaemia risk).
Patients with occurrence of a relapse less than six weeks prior to entry to study.
Previous treatment with beta-interferons or glatiramer acetate or steroids in the last three months.
Any previous treatment with mitoxantrone or other immunosuppressant.
Participants already taking supplemental vitamin D.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Hutchinson, MB, FRCP
Organizational Affiliation
St Vincent's University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Vincent's University Hospital
City
Dublin
State/Province
Dublin 4
Country
Ireland
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
all demographic details and outcome measures may be obtained directly from the PI by e-mail
Citations:
PubMed Identifier
23981773
Citation
O'Connell K, Kelly S, Kinsella K, Jordan S, Kenny O, Murphy D, Heffernan E, O'Laoide R, O'Shea D, McKenna C, Cassidy L, Fletcher J, Walsh C, Brady J, McGuigan C, Tubridy N, Hutchinson M. Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome and healthy control participants: study protocol for an exploratory randomized double- blind placebo-controlled trial. Trials. 2013 Aug 27;14:272. doi: 10.1186/1745-6215-14-272.
Results Reference
derived
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Dose-related Effects of Vitamin D3 on Immune Responses in Patients With Clinically Isolated Syndrome
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