Clinical trial NCT01728922: Dose-related Effects of Vitamin D3 on Immune Responses in Patients With Clinically Isolated Syndrome
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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Clinically Isolated Syndrome
Multiple Sclerosis
Keywords: Clinically isolated syndrome
Multiple sclerosis
Vitamin D
Immune response
CD4 T cell subsets
Cytokine
Lead sponsor: University College Dublin
Sponsor class: OTHER
Collaborators: name: University of Dublin, Trinity College
name: St Vincent's University Hospital, Ireland
First posted: 2012-11-20
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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:

1. 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
2. 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.

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.

Primary outcomes:
measure: 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.
timeFrame: This outcome measure will be assessed at baseline and at 24 weeks.
Secondary outcomes:
measure: The number of new T2 and gadolinium enhancing lesions compared to baseline amongst the study group.
timeFrame: Baseline and 24 weeks
measure: Relapse occurrence in the CIS patients during 24 weeks of the trial
timeFrame: At each clinic visit or as the need arises.
measure: 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).
timeFrame: At 24 weeks.
Other outcomes:
measure: Serum calcium
timeFrame: Every 4 weeks for 24 weeks
measure: 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
timeFrame: four weekly assessments over 24 weeks
measure: serum urea
timeFrame: 4 weekly over 24 weeks
measure: serum creatinine
timeFrame: 4 weekly over 24 weeks
measure: serum 25(OH)D levels
timeFrame: 4 weekly over 24 weeks
measure: serum parathormone (iPTH)
timeFrame: 4 weekly over 24 weeks
Locations:
city: Dublin
country: Ireland
facility: St Vincent's University Hospital
state: Dublin 4
Study officials:
affiliation: St Vincent's University Hospital
name: Michael Hutchinson, MB, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
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.