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
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Cholecalciferol (Vitamin D3); Placebo; Rebif
Intervention description: Subjects receive Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 44 mcg 3 times a week.; Subjects receive matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.; Subjects receive subcutaneous injection of Rebif 44 mcg 3 times weekly.
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Interferons; Interferon-beta; Interferon beta-1a
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 129.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Multiple Sclerosis Relapsing-Remitting; Relapsing Multiple Sclerosis (RMS); Rebif; Vitamin D3; Cholecalciferol

Summary:

      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 microgram (mcg) [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.
    

Eligibility 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 mcg (or 22 mcg in case of intolerance to 44 mcg) 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 less than (<) 75 nanomolar per liter (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, hypoparathyroidism, 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 greater than (>) 2.5 *
             upper limit of normal.

          -  Severe renal impairment defined as creatinine clearance below 30 milliliter per minute
             (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.