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

NCT ID: NCT01198132

Last Updated: 2017-12-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 129 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2015-11-30

Brief 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.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis Relapsing-Remitting; Relapsing Multiple Sclerosis (RMS); Rebif; Vitamin D3; Cholecalciferol

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

Cholecalciferol

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 3 times a week.

Group Type: EXPERIMENTAL

Cholecalciferol (Vitamin D3)

Intervention Type: DIETARY_SUPPLEMENT

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.

Rebif

Intervention Type: DRUG

Subjects receive subcutaneous injection of Rebif 44 mcg 3 times weekly.

Placebo

Subjects receive matching placebo to Cholecalciferol once every two weeks along with subcutaneous injection of Rebif 3 times weekly.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Subjects receive matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.

Rebif

Intervention Type: DRUG

Subjects receive subcutaneous injection of Rebif 44 mcg 3 times weekly.

Interventions

Cholecalciferol (Vitamin D3)

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.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Subjects receive matching placebo to Cholecalciferol once every two weeks orally along with subcutaneous injection of Rebif 44 mcg 3 times weekly.

Intervention Type: DIETARY_SUPPLEMENT

Rebif

Subjects receive subcutaneous injection of Rebif 44 mcg 3 times weekly.

Intervention Type: DRUG

Other Intervention Names

Vitamin D3; Interferon beta-1a

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Serono S.A.S, France

INDUSTRY

Sponsor Role: collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

CHU Hôpital Gui de Chauliac Service de Neurologie B

Montpellier, , France

Countries

France

References

Camu W, Lehert P, Pierrot-Deseilligny C, Hautecoeur P, Besserve A, Jean Deleglise AS, Payet M, Thouvenot E, Souberbielle JC. Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE). Neurol Neuroimmunol Neuroinflamm. 2019 Aug 6;6(5):e597. doi: 10.1212/NXI.0000000000000597. Print 2019 Sep.

Reference Type: DERIVED

PMID: 31454777 (View on PubMed)

Other Identifiers

2009-013695-46

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

701068-524

Identifier Type: -

Identifier Source: org_study_id