Effects of a Combined Supplementation of Conjugated Linoleic Acid (CLA) and Probiotics (Vivomixx®) as add-on to a First-line Immunotherapy in Relapsing-remitting Multiple Sclerosis

Study Overview
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Brief Summary
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The goal of this randomized, double-blind, placebo-controlled multicenter study is to investigate whether the combination of food supplementation with Tonalin® and specific probiotics is a safe and effective add-on to first-line disease modifying treatment (DMT, interferon-beta derivatives as well as glatirameracetate and other glatirameroids) in relapsing remitting MS (RRMS). 100 patients will be randomly assigned in a 1:1 ratio to receive either both food supplements for 48 weeks or to receive placebo in addition to their established first-line disease modifying treatment (DMT). The two randomized groups will be compared concerning the change in volume of T2-weighted hyperintense lesions from baseline to 48 weeks.

Official Title
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Effects of a Combined Supplementation of Conjugated Linoleic Acid (CLA/Tonalin® FFA 80) and Probiotics (Vivomixx®/VSL#3) as add-on to a First-line Immunotherapy in Relapsing-remitting Multiple Sclerosis

Conditions
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Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Dietary Supplement: Vivomixx®
* Dietary Supplement: Conjugated linoleic acid (CLA/Tonalin® FFA 80)
* Other: Maltose placebo
* Other: Sunflower oil placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsing-remitting multiple sclerosis according to current McDonald Criteria, EDSS maximal 5.5, 18-60 years stable treatment with first-line DMT (IFNbeta, teriflunomide or glatiramer acetate/ other glatirameroids) for at least 6 months absence of a clinical relapse for at least 3 months before inclusion Written informed consent Exclusion Criteria: diagnosis of primary or secondary progressive MS or other active autoimmune disease intake/administration of the following disease modifying therapies: at any time point: alemtuzumab, cladribine during the last 6 months before inclusion: natalizumab, fingolimod, dimethyl fumarate, siponimod during the last 12 months before inclusion: mitoxantron, ocrelizumab, ofatumumab, rituximab ingestion of other dietary supplementation (e.g. vitamins, probiotics, iron, calcium, prebiotics, such as omega-3-fatty acids) significant gastroenterological abnormality (e.g. inflammatory bowel disease, short bowel disease, preexisting digestive lesions) accompanying systemic immunosuppressive treatment relevant dietary restriction (e.g. strictly vegan nutrition) women during pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: two-arm, randomized, double-blind, placebo-controlled, multicenter
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dietary supplement<br>Vivomixx®/VSL#3 sachets p.o. (1.800 bio bacteria/d) and Conjugated linoleic acid (CLA/Tonalin® FFA 80) capsules p.o. (2 g/d) | Dietary Supplement: Vivomixx®<br>* Daily application of four sachets, i.e. 1.800 bio bacteria/day for 48 weeks<br>Dietary Supplement: Conjugated linoleic acid (CLA/Tonalin® FFA 80)<br>* Daily application of two capsules p.o., i.e. 2g/day for 48 weeks<br>|
| Placebo Comparator: Placebo-control<br>Maltose as Placebo to Vivomixx® and Sunflower oil as Placebo to Conjugated linoleic acid (CLA/Tonalin® FFA 80) | Other: Maltose placebo<br>* Daily application of four sachets for 48 weeks<br>Other: Sunflower oil placebo<br>* Daily application of two capsules p.o for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of volume of 'hyperintense lesions in the T2-weighted MRI images' between baseline and after 48 weeks of therapy | The two randomised study groups (intervention and placebo groups) are compared with regard to the change of volume of new or enlarged 'hyperintense lesions in the T2-weighted MRI images' (hereafter T2 lesions) between the start of the study and after 48 weeks. T2 lesions were chosen as primary endpoint as this has been used as a surrogate marker of efficacy in several recent MS studies | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in T2 lesions at 48 weeks compared to baseline | Change in T2 lesions at 48 weeks compared to baseline (yes/no) | 48 weeks | 
| Number of new or enlarging T2-weighted hyperintense lesions | Number of new or enlarging T2-weighted hyperintense lesions based on the comparison of brain MRI-scans after 48 weeks of intervention as compared to baseline | 48 weeks | 
| Volume of new or enlarged 'hyperintense lesions in the T2-weighted MRI images' as well as double inversion recovery (DIR) images | Volume of new or enlarged 'hyperintense lesions in the T2-weighted MRI images' as well as double inversion recovery (DIR) images will be compared between the intervention arm and the placebo arm. This approach has been recently published and rises the probability to detect new brain lesions in MS without application of gadolinium with a sensitivity of 98.1% | 48 weeks | 
| Annualized relapse rate | All relapses confirmed by a physician will be documented and analysed. Clinical relapses are defined as onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by objective abnormalities on a neurological examination, which are not explained solely by non-MS processes such as fever, infection, severe stress or drug toxicity. Annualized relapse rates are compared between the two study groups. | 48 weeks |