Back to resultsEffects 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 (CLAProMS)
Primary Purpose
Multiple Sclerosis, Relapsing-Remitting
Status
Not yet recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Vivomixx®
Conjugated linoleic acid (CLA/Tonalin® FFA 80)
Maltose placebo
Sunflower oil placebo
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis, Relapsing-Remitting
Eligibility Criteria
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
Sites / Locations
- Neuroimmune outpatient clinic, Institute of Clinical Neuroimmunology
- Neurological study centre, Department of Neurology
- IIT unit of the Department of Neurology with Institute of Translational Neurology
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Dietary supplement
Placebo-control
Arm Description
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)
Maltose as Placebo to Vivomixx® and Sunflower oil as Placebo to Conjugated linoleic acid (CLA/Tonalin® FFA 80)
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Change in T2 lesions at 48 weeks compared to baseline
Change in T2 lesions at 48 weeks compared to baseline (yes/no)
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
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%
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.
Full Information
NCT ID
NCT05920018
First Posted
May 2, 2023
Last Updated
June 15, 2023
Sponsor
Westfälische Wilhelms-Universität Münster
1. Study Identification
Unique Protocol Identification Number
NCT05920018
Brief Title
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
Acronym
CLAProMS
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 2023 (Anticipated)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Westfälische Wilhelms-Universität Münster
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Relapsing-Remitting
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
two-arm, randomized, double-blind, placebo-controlled, multicenter
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Patients will be randomized after successful screening and inclusion. They will be randomized with a 1:1 ratio to receive either conjugated linoleic acid (CLA/Tonalin®) and probiotics (Vivomixx®) or the corresponding placebos as add-on therapy. Randomization will be stratified according to first-line therapy with Interferon-beta, Glatirameracetat / other glatirameroids, or Teriflunomid.
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dietary supplement
Arm Type
Active Comparator
Arm Description
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)
Arm Title
Placebo-control
Arm Type
Placebo Comparator
Arm Description
Maltose as Placebo to Vivomixx® and
Sunflower oil as Placebo to Conjugated linoleic acid (CLA/Tonalin® FFA 80)
Intervention Type
Dietary Supplement
Intervention Name(s)
Vivomixx®
Intervention Description
Daily application of four sachets, i.e. 1.800 bio bacteria/day for 48 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
Conjugated linoleic acid (CLA/Tonalin® FFA 80)
Intervention Description
Daily application of two capsules p.o., i.e. 2g/day for 48 weeks
Intervention Type
Other
Intervention Name(s)
Maltose placebo
Intervention Description
Daily application of four sachets for 48 weeks
Intervention Type
Other
Intervention Name(s)
Sunflower oil placebo
Intervention Description
Daily application of two capsules p.o for 48 weeks
Primary Outcome Measure Information:
Title
Change of volume of 'hyperintense lesions in the T2-weighted MRI images' between baseline and after 48 weeks of therapy
Description
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
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Change in T2 lesions at 48 weeks compared to baseline
Description
Change in T2 lesions at 48 weeks compared to baseline (yes/no)
Time Frame
48 weeks
Title
Number of new or enlarging T2-weighted hyperintense lesions
Description
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
Time Frame
48 weeks
Title
Volume of new or enlarged 'hyperintense lesions in the T2-weighted MRI images' as well as double inversion recovery (DIR) images
Description
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%
Time Frame
48 weeks
Title
Annualized relapse rate
Description
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.
Time Frame
48 weeks
Other Pre-specified Outcome Measures:
Title
Disease progression throughout the study
Description
Disease progression throughout the study will be documented by assessment of the Expanded Disability Status Scale (EDSS) at baseline and at 48 weeks of the study as well as in case of unscheduled visits such as in case of a relapse. EDSS is a standardized measure of MS-related disability and a key endpoint in many clinical trials in MS.
Time Frame
48 weeks
Title
Assessment of patient-reported outcomes (PRO) and quality of life via MSIS-29 (Multiple Sclerosis Impact Scale)
Description
Assessment of patient-reported outcomes (PRO) and quality of life by use of the following validated and commonly used questionnaires:
MSIS-29 (Multiple Sclerosis Impact Scale) to assess quality of life Patients will be asked to fill in this questionnaires at baseline, after 24 weeks of therapy and after 48 weeks of therapy. These additional outcomes are clinically relevant as the EDSS preferentially focuses on motor function with predominance of the lower limb.
Time Frame
48 weeks
Title
Assessment of patient-reported outcomes (PRO) and quality of life via FSMC (Fatigue Scale for Motion and Cognition)
Description
Assessment of patient-reported outcomes (PRO) and quality of life by use of the following validated and commonly used questionnaires:
FSMC (Fatigue Scale for Motion and Cognition) to assess MS-related fatigue Patients will be asked to fill in this questionnaires at baseline, after 24 weeks of therapy and after 48 weeks of therapy. These additional outcomes are clinically relevant as the EDSS preferentially focuses on motor function with predominance of the lower limb.
Time Frame
48 weeks
Title
Assessment of patient-reported outcomes (PRO) and quality of life via SDMT (Symbol-Digit Modalities Test)
Description
Assessment of patient-reported outcomes (PRO) and quality of life by use of the following validated and commonly used questionnaires:
SDMT (Symbol-Digit Modalities Test) to assess MS-related cognition Patients will be asked to fill in this questionnaires at baseline, after 24 weeks of therapy and after 48 weeks of therapy. These additional outcomes are clinically relevant as the EDSS preferentially focuses on motor function with predominance of the lower limb.
Time Frame
48 weeks
Title
Assessment of patient-reported outcomes (PRO) and quality of life via HADS (Hospital Anxiety and Depression Scale)
Description
Assessment of patient-reported outcomes (PRO) and quality of life by use of the following validated and commonly used questionnaires:
HADS (Hospital Anxiety and Depression Scale) to assess concomitant psychiatric symptoms Patients will be asked to fill in this questionnaires at baseline, after 24 weeks of therapy and after 48 weeks of therapy. These additional outcomes are clinically relevant as the EDSS preferentially focuses on motor function with predominance of the lower limb.
Time Frame
48 weeks
Title
Assessment of patient-reported outcomes (PRO) and quality of life via BDI-II (Beck's Depression Inventory)
Description
Assessment of patient-reported outcomes (PRO) and quality of life by use of the following validated and commonly used questionnaires:
BDI-II (Beck's Depression Inventory) to assess concomitant psychiatric symptoms Patients will be asked to fill in this questionnaires at baseline, after 24 weeks of therapy and after 48 weeks of therapy. These additional outcomes are clinically relevant as the EDSS preferentially focuses on motor function with predominance of the lower limb.
Time Frame
48 weeks
Title
Assessment of patient-reported outcomes (PRO) and quality of life via TSQM-9 (Treatment Satisfaction Questionnaire for Medication)
Description
Assessment of patient-reported outcomes (PRO) and quality of life by use of the following validated and commonly used questionnaires:
TSQM-9 (Treatment Satisfaction Questionnaire for Medication) to assess treatment satisfaction Patients will be asked to fill in this questionnaires at baseline, after 24 weeks of therapy and after 48 weeks of therapy. These additional outcomes are clinically relevant as the EDSS preferentially focuses on motor function with predominance of the lower limb.
Time Frame
48 weeks
Title
Changes in key peripheral blood immune signatures
Description
Highly standardized flow-cytometry of PBMC will be performed in order to determine treatment-related changes in peripheral immune signatures.
Time Frame
48 weeks
Title
Focus on signs of gastrointestinal and systemic side effects
Description
The rate and nature of adverse events, changes in vital signs and physical examinations, and abnormal laboratory results will be documented and analysed.
Time Frame
48 weeks
Title
Functional characterization of human myeloid cells
Description
A comprehensive and detailed characterization of all major immune cell populations of the peripheral blood will be done. In addition a characterization of their maturity status, their activation state, as well as certain functional properties including cytokine production as well as production of cytolytic molecules will be assessed. The aim of the immunological analysis of peripheral blood immune signatures is to investigate whether a change in the composition and activation state of the immune cells in the peripheral blood can be observed as a consequence of the combined intervention with Tonalin® and Vivomixx® as compared to the placebo group. A particular focus will be on the reduction in proinflammatory properties of different myeloid cell populations, based on our preliminary work. The different immune cell populations will be analyzed both as percentages and as absolute cell numbers.
Time Frame
48 weeks
Title
Correlation of identified immunological effects with main endpoints of MRI and clinical efficacy
Description
The correlation of identified immunological effects with main endpoints of MRI (including rate of global brain and grey matter atrophy derived from structural MRI) and clinical efficacy will be analysed using multivariable regression methods or machine learning approaches.
Time Frame
48 weeks
Title
Changes in diffuse white matter damage (measured by fractional anisotropy FA)
Description
Changes in diffuse white matter damage (measured by fractional anisotropy FA)
Time Frame
48 weeks
Title
Global brain atrophy, grey matter atrophy and white matter atrophy
Description
Rate of global brain and grey matter atrophy derived from structural MRI.
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Luisa Klotz, Prof.
Phone
+49 (0)251 83
Ext
48165
Email
MS-Studienambulanz@ukmuenster.de
First Name & Middle Initial & Last Name or Official Title & Degree
Jan Lünemann, Prof.
Phone
+49 (0)251 83
Ext
48165
Email
MS-Studienambulanz@ukmuenster.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luisa Klotz, Prof.
Organizational Affiliation
Westfälische Wilhelms-Universität Münster
Official's Role
Principal Investigator
Facility Information:
Facility Name
Neuroimmune outpatient clinic, Institute of Clinical Neuroimmunology
City
Munich
State/Province
Bavaria
Country
Germany
Facility Name
Neurological study centre, Department of Neurology
City
Mainz
State/Province
Hessen
Country
Germany
Facility Name
IIT unit of the Department of Neurology with Institute of Translational Neurology
City
Münster
State/Province
NRW
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luisa Klotz, Prof.
Phone
+4925183
Ext
48165
Email
luisa.klotz@ukmuenster.de
12. IPD Sharing Statement
Learn more about this trial
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
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