Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome or early multiple sclerosis and healthy control participants. An exploratory randomised double blind placebo controlled study

INTERVENTION: Trade Name: Vigantol Product Name: N/A Product Code: N/A Pharmaceutical Form: Oral drops, solution Pharmaceutical form of the placebo: Oral drops, solution Route of administration of the placebo: Oral use CONDITION: Multiple Sclerosis ; MedDRA version: 14.1 Level: HLT Classification code 10052785 Term: Multiple sclerosis acute and progressive System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: To determine the effects of vitamin D supplementation at two doses a) 4,667 IU daily b) 9,333 IU daily compared to c) placebo over a four and six‐month period on the frequency of CD4 T cell subsets and cytokine responses by PBMC in 1) patients with the clinically isolated syndrome or early MS not treated with disease modifying therapies 2) healthy control participants; Primary end point(s): 1 Primary endpoint: To determine the effects of vitamin D supplementation at two doses a) 4,667 IU daily b) 9,333 IU daily compared to c) placebo over a four and six‐month period on the frequency of CD4 T cell subsets and cytokine responses by PBMC in 1) patients with the clinically isolated syndrome (CIS) or early MS not treated with disease modifying therapies (DMTs) 2) healthy control participants Secondary Objective: 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 four and six months on the frequency of CD4 T cell subsets and cytokine responses by PBMC in 1) patients with the clinically isolated syndrome (CIS) or early MS not treated with disease modifying therapies (DMTs) 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 on MRI scanning at six months compared to baseline b) freedom from relapses in treated (both 5,000 IU and 10,000 IU) CIS/MS patients versus CIS/MS patients receiving placebo.; Timepoint(s) of evaluation of this end point: Six months SECONDARY OUTCOME: Secondary end point(s): 1) To determine whether there is a dose response effect of supplementation using 4,667 IU and 9,333 IU of vitamin D versus placebo over four and six months on the frequency of CD4 T cell subsets and cytokine responses by PBMC in 1) patients with the clinically isolated syndrome (CIS) or early MS not treated with disease modifying therapies (DMTs) 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 on MRI scanning at six months compared to baseline b) freedom from relapses in treated (both 5,000 IU and 10,000 IU) CIS/MS patients versus CIS/MS patients receiving placebo. ; Timepoint(s) of evaluation of this end point: Six months INCLUSION CRITERIA: a) Healthy volunteer participants. The healthy control subjects will be specifically recruited from and junior hospital doctors, nursing and administrative staff at St Vincent's University Hospital in the age range 25‐40 years since the CIS/MS population will have a mean age of 30‐32 years based on natural history data. The gender ratio of the control subjects will be 2:1: F: M since that is the ratio found in MS/CIS patients. b) Patients (n=45) with a clinically isolated syndrome and two or more than two T2 lesions on MRI brain scan or relapsing‐remitting MS (McDonald’s criteria) within 5 years of onset, aged 18‐55yrs and not receiving any disease modifying therapy. d) Written informed consent from all participants (patients c) Although vitamin D has no effect on pregnancy, pregnancy affects MS activity and immunological measures, thus female CIS/MS patients and control participants will be requested to avoid becoming pregnant during the study.