Dose-related Effects of Vitamin D3 on Immune Responses in Patients With Clinically Isolated Syndrome

NCT01728922 | Completed Phase 1 DMC

• 1 other identifier: 2012CIS/VD/SVUH
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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

Conditions

Clinically Isolated Syndrome; Multiple Sclerosis

Keywords

Clinically isolated syndrome; Multiple sclerosis; Vitamin D; Immune response; CD4 T cell subsets; Cytokine

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (3)

• The number of new T2 and gadolinium enhancing lesions compared to baseline amongst the study group.

  Baseline and 24 weeks

• Relapse occurrence in the CIS patients during 24 weeks of the trial

  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.

Other Outcomes (6)

• Serum calcium

  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

  four weekly assessments over 24 weeks

• serum urea

  4 weekly over 24 weeks

Study Arms (6)

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.

Dietary Supplement: 5000IU vitamin D

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.

Dietary Supplement: 10000IU vitamin D

CIS - placebo

PLACEBO COMPARATOR

15 patients will be administered placebo and all outcome measures will be assessed.

Other: Placebo

CIS - 5,000 IU vitamin D

ACTIVE COMPARATOR

15 patients will be administered 5,000 IU vitamin D and all outcomes will be assessed.

Dietary Supplement: 5000IU vitamin D

CIS - 10,000 IU vitamin D

ACTIVE COMPARATOR

15 patients will be administered 10,000 IU of vitamin D and all outcome measures assessed.

Dietary Supplement: 10000IU vitamin D

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.

Other: Placebo

Interventions

5000IU vitamin D DIETARY_SUPPLEMENT

Vigantol Oil

Also known as: Vigantol Oil

CIS - 5,000 IU vitamin D; Healthy control - 5,000 IU vitamin D

10000IU vitamin D DIETARY_SUPPLEMENT

Vigantol Oil

Also known as: Vigantol Oil

CIS - 10,000 IU vitamin D; Healthy control - 10,000 IU vitamin D

Placebo OTHER

Placebo Oil

Also known as: Placebo Oil

CIS - placebo; Healthy control - placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University College Dublin: lead
• University of Dublin, Trinity College: collaborator
• St Vincent's University Hospital, Ireland: collaborator

Study Sites (1)

St Vincent's University Hospital

Dublin, Dublin 4, Ireland

Location

Related Publications (1)

• 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.

  PMID: 23981773 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Vitamin D

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Michael Hutchinson, MB, FRCP

  St Vincent's University Hospital, Ireland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: similar appearance of placebo and active drug
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Neurologist, Newman Clinical Research Professor

Model Details: double-blind, dose ranging, two doses of vitamin D, randomised parallel groups with placebo arms in clinically isolated syndrome and heathy control participants

Study Record Dates

• First Submitted: November 8, 2012
• First Posted: November 20, 2012
• Study Start: November 6, 2012
• Primary Completion: June 5, 2015
• Study Completion: June 5, 2016
• Last Updated: May 3, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

IE (1)