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

NCT01198132 | Completed Phase 2 Results DMC

• 2 other identifiers: 701068-5242009-013695-46
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Annualized Relapse Rate

  The annualized relapse rate was calculated for each treatment group as follows: the number of relapses observed during the study period divided by the time spent in the study (in years).

  2 years post treatment (IMP) administration

Secondary Outcomes (9)

• Time to First Documented Relapse

  2 years post treatment (IMP) administration

• Mean Number of Relapses Per Subject

  2 years post treatment (IMP) administration

• Number of Relapse-Free (Documented) Subjects

  2 years post treatment (IMP) administration

• Cumulative Probability of Progression of Disability (Kaplan-Meier Curves)

  Baseline up to week 96

• Number of New or Extended Lesions by T1- and T2-Weighted Magnetic Resonance Imaging (MRI)

  2 years post treatment (IMP) administration

Study Arms (2)

Cholecalciferol

EXPERIMENTAL

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.

Dietary Supplement: Cholecalciferol (Vitamin D3); Drug: Rebif

Placebo

PLACEBO COMPARATOR

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

Dietary Supplement: Placebo; Drug: Rebif

Interventions

Cholecalciferol (Vitamin D3) 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.

Also known as: Vitamin D3

Cholecalciferol

Placebo DIETARY_SUPPLEMENT

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

Placebo

Rebif DRUG

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

Also known as: Interferon beta-1a

Cholecalciferol; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Merck Serono S.A.S, France: collaborator

Study Sites (1)

CHU Hôpital Gui de Chauliac Service de Neurologie B

Montpellier, France

Location

Related Publications (1)

• 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.

  PMID: 31454777 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Interventions

Cholecalciferol; Interferon beta-1a

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)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Title: Merck KGaA Communication Center
• Organization: Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2010
• First Posted: September 9, 2010
• Study Start: November 1, 2009
• Primary Completion: March 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 14, 2017
• Results First Posted: December 14, 2017

Record last verified: 2017-05

Locations

FR (1)