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| Name | Class |
|---|---|
| University of Dublin, Trinity College | OTHER |
| St Vincent's University Hospital, Ireland | OTHER |
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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
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy control - 5,000 IU vitamin D | Active Comparator | 13 healthy controls will be administered 5,000 IU vitamin D. Primary outcome and safety outcome measures will be assessed. |
|
| Healthy control - 10,000 IU vitamin D | Active Comparator | 13 healthy controls will be administered 10,000 IU vitamin D. Primary outcome and safety outcome measures will be assessed. |
|
| CIS - placebo | Placebo Comparator | 15 patients will be administered placebo and all outcome measures will be assessed. |
|
| CIS - 5,000 IU vitamin D | Active Comparator | 15 patients will be administered 5,000 IU vitamin D and all outcomes will be assessed. |
|
| CIS - 10,000 IU vitamin D | Active Comparator | 15 patients will be administered 10,000 IU of vitamin D and all outcome measures assessed. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5000IU vitamin D | Dietary Supplement | Vigantol Oil |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | This outcome measure will be assessed at baseline and at 24 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Serum calcium | a measure of calcium homeostasis | Every 4 weeks for 24 weeks |
| 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 |
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).
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Hutchinson, MB, FRCP | St Vincent's University Hospital, Ireland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St Vincent's University Hospital | Dublin | Dublin 4 | Ireland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23981773 | Derived | 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. |
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all demographic details and outcome measures may be obtained directly from the PI by e-mail
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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| ID | Term |
|---|---|
| D014807 | Vitamin D |
| ID | Term |
|---|---|
| D012632 | Secosteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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double-blind, dose ranging, two doses of vitamin D, randomised parallel groups with placebo arms in clinically isolated syndrome and heathy control participants
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similar appearance of placebo and active drug
| Healthy control - placebo |
| Placebo Comparator |
13 control participants who will be administered placebo. These will be assessed for the primary outcome and safety outcomes only. |
|
| 10000IU vitamin D | Dietary Supplement | Vigantol Oil |
|
|
| Placebo | Other | Placebo Oil |
|
|
| Baseline and 24 weeks |
| 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. | At each clinic visit or as the need arises. |
| 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). | At 24 weeks. |
| four weekly assessments over 24 weeks |
| serum urea | a measure of renal function | 4 weekly over 24 weeks |
| serum creatinine | a measure of renal function | 4 weekly over 24 weeks |
| serum 25(OH)D levels | a measure of response to oral dosing and adherence to therapy. | 4 weekly over 24 weeks |
| serum parathormone (iPTH) | a measure of parathyroid function | 4 weekly over 24 weeks |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |