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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 129
- 试验地点
- 1
- 主要终点
- Annualized Relapse Rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Cholecalciferol (Vitamin D3) (Dietary Supplement)
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.
干预措施: Rebif (Drug)
Placebo
Subjects receive matching placebo to Cholecalciferol once every two weeks along with subcutaneous injection of Rebif 3 times weekly.
干预措施: Placebo (Dietary Supplement)
Placebo
Subjects receive matching placebo to Cholecalciferol once every two weeks along with subcutaneous injection of Rebif 3 times weekly.
干预措施: Rebif (Drug)
结局指标
主要结局
Annualized Relapse Rate
时间窗: 2 years post treatment (IMP) administration
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).
次要结局
- 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)
- Changes From Baseline in Measured Lesion Load (T2)(Baseline, Week 96)
- Change From Baseline in Measurement and Evaluation of Cognitive Ability by Paced Auditory Serial Addition Task (PASAT) Total Score At Week 96(Baseline, Week 96)
- Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L)(2 years post treatment (IMP) administration)
- Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Abnormal Clinical Laboratory(Baseline up to end of treatment (week 96))