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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01198132
• Date of registration: 08/09/2010
• Prospective Registration: No
• Primary sponsor: Merck KGaA
• Public title: 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
• Scientific 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
• Date of first enrolment: November 2009
• Target sample size: 129
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01198132
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Supportive Care. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Medical Responsible
• Affiliation: Merck KGaA

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Intervention(s)

Dietary Supplement: Placebo

Dietary Supplement: Cholecalciferol (Vitamin D3)

Drug: Rebif

Primary Outcome(s)

Annualized Relapse Rate [Time Frame: 2 years post treatment (IMP) administration]

Secondary Outcome(s)

Change From Baseline in Measurement and Evaluation of Cognitive Ability by Paced Auditory Serial Addition Task (PASAT) Total Score At Week 96 [Time Frame: Baseline, Week 96]

Cumulative Probability of Progression of Disability (Kaplan-Meier Curves) [Time Frame: Baseline up to week 96]

Number of Relapse-Free (Documented) Subjects [Time Frame: 2 years post treatment (IMP) administration]

Time to First Documented Relapse [Time Frame: 2 years post treatment (IMP) administration]

Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Abnormal Clinical Laboratory [Time Frame: Baseline up to end of treatment (week 96)]

Changes From Baseline in Measured Lesion Load (T2) [Time Frame: Baseline, Week 96]

Mean Number of Relapses Per Subject [Time Frame: 2 years post treatment (IMP) administration]

Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L) [Time Frame: 2 years post treatment (IMP) administration]

Number of New or Extended Lesions by T1- and T2-Weighted Magnetic Resonance Imaging (MRI) [Time Frame: 2 years post treatment (IMP) administration]

Secondary ID(s)

2009-013695-46

701068-524

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Merck Serono S.A.S, France

Results

• Results available: Yes
• Date Posted: 14/12/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01198132