A Multicentre Study of the Efficacy and Safety of Supplementary Treatment With Cholecalciferol in Patients With Relapsing Multiple Sclerosis Treated With Subcutaneous Interferon Beta-1a 44 µg 3 Times Weekly (CHOLINE)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Merck Serono S.A.S, France
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01198132
First received: September 8, 2010
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

The aim of this multicentre, randomised, double-blind, placebo-controlled study is to evaluate the efficacy and safety of supplementary treatment with cholecalciferol (vitamin D3) in subjects with relapsing multiple sclerosis (R MS) treated with subcutaneous (s.c.) interferon beta-1a 44 µg (Rebif) 3 times weekly. The subjects will be divided into 2 groups, one receiving cholecalciferol 100,000 IU twice monthly along with Rebif treatment and the other group will be on placebo along with Rebif treatment. A total of 200 subjects will be recruited in 20-30 centres in France.


Condition Intervention Phase
Multiple Sclerosis
Dietary Supplement: Cholecalciferol (Vitamin D3)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: A Multicentre, Randomised, Double-blind, Placebo-controlled Study of the Efficacy of Supplementary Treatment With Cholecalciferol (Vitamin D3) in Patients With Relapsing- Multiple Sclerosis (RMS) Treated With Subcutaneous Interferon Beta-1a 44 µg 3 Times Weekly

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Reduction in rate of relapse [ Time Frame: After 2 years of treatment ] [ Designated as safety issue: No ]
    Relapse rate is expressed as percentage difference between the two groups


Secondary Outcome Measures:
  • Time to first documented relapse [ Time Frame: After 2 years of treatment ] [ Designated as safety issue: No ]
  • Mean number of relapses per subject per year [ Time Frame: After 2 years of treatment ] [ Designated as safety issue: No ]
  • Number of relapse-free (documented) subjects [ Time Frame: after two years of treatment ] [ Designated as safety issue: No ]
  • Cumulative probability of progression of disability (Kaplan-Meier curves) [ Time Frame: After 2 years of treatment ] [ Designated as safety issue: No ]
  • Number of new or extended lesions by T1- and T2-weighted MRI [ Time Frame: After 2 years of treatment ] [ Designated as safety issue: No ]
  • Changes in measured lesion load (T2) [ Time Frame: After 2 years of treatment ] [ Designated as safety issue: No ]
  • Measurement and evaluation of cognitive ability by Paced auditory serial addition task (PASAT) [ Time Frame: After 2 years of treatment ] [ Designated as safety issue: No ]
  • Change in quality of life (QoL) using EQ-5D (EuroQoL-5 dimension questionnaire) [ Time Frame: After 2 years of treatment ] [ Designated as safety issue: No ]
  • Safety of the treatment assessed by recording of adverse events, clinical laboratory evaluations (blood biochemistry and urinalysis) and vital signs [ Time Frame: After 2 years of treatment ] [ Designated as safety issue: Yes ]

Enrollment: 129
Study Start Date: January 2010
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
100 subjects will receive 100,000 IU twice monthly, i.e. one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) during the 96 weeks treatment period along with s.c. Rebif 3 times weekly.
Dietary Supplement: Cholecalciferol (Vitamin D3)
Subjects will be receiving 100 000 International units (IU - 1 IU is biological equivalent of 0.025µg cholecalciferol) twice monthly, i.e. one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) during the 24-month period.
Other Name: Vitamin D3
No Intervention: Group 2
100 subjects will receive the placebo under identical conditions along with s.c. Rebif 3 times weekly.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of RRMS according to Poser criteria (clinically definite multiple sclerosis [CDMS] or laboratory supported definite multiple sclerosis [LSDMS]) or according to McDonald criteria (2005).
  • Subjects aged between 18 and 65 years.
  • Treated with interferon beta-1a 44 µg (or 22 µg in case of intolerance to 44 µg) 3 times weekly subcutaneously for 4 months ± (2 months) at the randomization visit (V1).
  • Expanded disability status scale (EDSS) score between 0 and 5.
  • At least one documented episode during the last two year.
  • Stable disease with no episodes over the last 30 days.
  • Serum 25-hydroxyvitamin D < 75 nmol/l at randomization visit.
  • Women must not be pregnant or breast-feeding, and women of childbearing age must meet the following criteria:

    • Surgically sterilised, or
    • Using a highly effective contraceptive method throughout the entire duration of the study. A highly effective contraceptive method is defined as a method with a very low failure rate (i.e. < 1 % per year) with regular and appropriate use, e.g. implants, injectable contraceptives, combined oral contraceptives, coil, abstinence or vasectomised partner.
    • Menopausal women may be included.
  • Affiliated to French healthcare insurance.
  • Subjects must be ready and able to provide informed consent and comply with the protocol requirements.

Exclusion Criteria:

  • Hormonal abnormalities associated with vitamin D other than low dietary intake or reduced exposure to sun, for example malabsorption (coeliac disease, Whipple's disease, inflammatory bowel disease, intestinal derivation, short bowel syndrome), cirrhosis, nephrotic syndrome, hyperthyroidism, rickets, hypoparathyreosis, cancer, granulomatous diseases (sarcoidosis, silicosis) and lymphomas known at the initial visit.
  • Patients with osteoporosis or known osteopenia.
  • Use of medicines affecting vitamin D metabolism other than corticosteroids, e.g. anticonvulsants (phenobarbital, primidone, phenytoin), rifampicin, isoniazid, ketoconazole, 5-FU and leucovorin, or thiazide diuretics.
  • Previous or ongoing hypercalcaemia.
  • Situations involving increased susceptibility to hypercalcaemia, e.g. known cardiac arrhythmia or cardiac disease, treatment with digitalis, renal lithiasis.
  • Any contraindication to the treatment (cholecalciferol) stated in the summary of product characteristics.
  • Moderate renal impairment defined as creatinine clearance between 30 and 60 ml/min.
  • An active episode during the month prior to inclusion in the study.
  • Inadequate liver function, defined as total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase > 2.5 * upper limit of normal.
  • Severe renal impairment defined as creatinine clearance below 30 ml/min.
  • Inadequate marrow reserves, defined as white blood cells < 0.5 * lower limit of normal.
  • Serious or acute heart disease such as uncontrolled cardiac arrhythmia, uncontrolled angina, cardiomyopathy or uncontrolled congestive heart failure.
  • History of severe depression, or attempted suicide or ongoing suicidal ideation.
  • Epilepsy inadequately controlled by treatment.
  • Ongoing or previous alcohol or drug abuse (within the last two years).
  • Major medical or psychiatric disease which, in the opinion of investigator, would place the subject at risk or could adversely affect compliance with the study protocol.
  • Known hypersensitivity to gadolinium and/or known inability to undergo MRI.
  • Any medical condition requiring chronic treatment with systemic corticosteroids.
  • Participation in any other studies involving other study products over the 30 days prior to inclusion in this study.
  • Legal incapacity or limited legal capacity.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01198132

Locations
France
CHU Hôpital Gui de Chauliac Service de Neurologie B
Montpellier, France
Sponsors and Collaborators
Merck KGaA
Merck Serono S.A.S, France
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01198132     History of Changes
Other Study ID Numbers: 701068-524, 2009-013695-46
Study First Received: September 8, 2010
Last Updated: February 3, 2014
Health Authority: France: ANSM Agence Nationale de Sécurité du Médicament et des produits de santé (Saint-Denis)

Keywords provided by Merck KGaA:
Multiple Sclerosis Relapsing-Remitting
Relapsing Multiple Sclerosis (RMS)
Rebif
Vitamin D3
Cholecalciferol

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Interferon-beta
Interferons
Interferon beta 1a
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Micronutrients
Growth Substances
Bone Density Conservation Agents
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 26, 2014