- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02403947
MEsenchymal StEm Cells for Multiple Sclerosis (MESEMS)
Treatment of Multiple Sclerosis With Mesenchymal Stem Cells: Phase I/II Study
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), which ultimately leads to myelin damage and axonal loss. The disease is complex and multifactorial, but the key pathogenic event appears to be an uncontrolled response of components of the immune system (T and B lymphocytes) to myelin proteins. No definitive treatment is available for MS, however immunomodulatory and immunosuppressant drugs act as disease-modifying agents (DMDs).
Unfortunately, the current treatments demonstrate partial efficacy in targeting the deleterious immune reactions. According to the present knowledge of the pathophysiology of MS, an ideal therapeutic strategy would be to modulate or suppress the aggressive immune process, to protect axons and neurons from degeneration, and to enhance repair and facilitate remyelination.
A specific form of stem cells, called adult mesenchymal stem cells (MSCs), has shown remarkable ability to modulate the immune response. This study will evaluate the safety of injecting MSCs in people with MS.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Toulouse, France, 31059
- Purpan Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18 to 50 years
- Disease duration 2 to 10 years (included)
- Diagnosis of MS
Relapsing remitting MS (RRMS) not responding to at least a year of attempted therapy with one or more of the approved therapies (beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by one or more of the following:
- more or egal 1 clinically documented relapse in past 12 months
- more or egal 2 clinically documented relapses in last 24 months
- more or egal 1 GEL at MRI performed within the last 12 months
Secondary progressive MS (SPMS) not responding to at least a year of attempted therapy with one or more of the approved therapies (beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by both::
- With more or egal 1 clinically documented relapse in the last twelve months
- Without on-going relapses, but with more or egal 1 GEL at MRI performed within the last 12 months.
Primary progressive MS (PPMS) patients with all the following features:
- an increase ofmore or egal 1 EDSS point (if at inclusion EDSS inferior or egal 5.0) or 0.5 EDSS point (if at inclusion EDSS more or egal 5.5), in the last twelve months
- more or egal 1 GEL at MRI performed within the last 12 months
Positive cerebrospinal fluid (CSF) (oligoclonal banding).
- EDSS (Expanded Disability Status Scale) 3.0 to 6.5
- Women of childbearing age with an effective contraception.
Exclusion Criteria:
- RRMS not fulfilling inclusion criteria
- SPMS not fulfilling inclusion criteria
- PPMS not fulfilling inclusion criteria
- Inferior to 3 months since treatment with any immunosuppressive therapy including natalizumab and fingolimod
- Inferior or egal to 1 month since last treatment with interferon-beta or glatiramer acetate
- Corticosteroid treatment Inferior or egal to 30 days
- Relapse inferior or egal to 60 days
- Any active or chronic infection including infection with HIV1-2 (Human Immunodeficiency Virus 2) or HTLV I-II (Human T-lymphotropic virus I-II) or Syphilis or chronic Hepatitis B or Hepatitis C inferior to 1 month
- Previous history of a malignancy other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year
- Severely limited life expectancy by another co-morbid illness
- History of previous diagnosis of myelodysplasia or previous hematologic disease or current clinically relevant abnormalities of white blood cell counts
- Pregnancy or risk or pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study)**
- eGFR (estimated Glomerular Filtration Rate ) inferior to 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination.
- Inability to give written informed consent in accordance with research ethics board guidelines.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Suspension media
At week 0 a single infusion of either ex-vivo expanded autologous MSC or suspension media will be administered intravenously at a dose of 1-2 x 1000000 MSC/Kg body weight.
At week 24, another infusion will be performed for cross-over re-treatment: at week 24 treatments will be reversed compared to week 0
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injection suspension media
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Experimental: Mesenchymal stem cells
At week 0 a single infusion of either ex-vivo expanded autologous MSC or suspension media will be administered intravenously at a dose of 1-2 x 1000000 MSC/Kg body weight.
At week 24, another infusion will be performed for cross-over re-treatment: at week 24 treatments will be reversed compared to week 0
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After the sampling of bone-marrow and culture of MSCs by the French Blood Establishment (Midi-Pyrénées), patients will receive an IV injection of MSCs.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of MSCs infusion, number, timeframe of occurrence and severity of Adverse Events
Time Frame: 24 weeks from the first infusion
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Safety assessed by number, timeframe of occurrence and severity of Adverse Events
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24 weeks from the first infusion
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efficacy: number of contrast-enhancing lesions (GEL) at MRI scan
Time Frame: 24 weeks from the first infusion
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total number of contrast-enhancing lesions (GEL) at MRI scan
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24 weeks from the first infusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy of the experimental treatment in term of combined MRI activity
Time Frame: 48 weeks from the first infusion
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Number of GEL counted over week 28, 36 and 48 compared with the number of GEL counted over 4, 12 and 24 weeks.
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48 weeks from the first infusion
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Efficacy assessed by combined unique MRI activity, volume of GEL, and volume of BH
Time Frame: 24 weeks from the first infusion
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Combined unique MRI activity (number of new or enlarging T2, or enhancing or re-enhancing lesions), volume of GEL and volume of black holes (BH) over 4, 12, 24 weeks compared between treatment groups.
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24 weeks from the first infusion
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Efficacy assessed by combined unique MRI activity, volume of GEL and volume of BH
Time Frame: 48 weeks from the first infusion
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Combined unique MRI activity, volume of GEL and volume of BH over week 28, 36 and 48 compared with the same outcomes over 4, 12 and 24 weeks.
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48 weeks from the first infusion
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Efficacy: Number of relapses
Time Frame: 24 weeks from the first infusion
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Number of relapses in MSC treatment group vs. placebo group in the first 24 weeks and after cross-over re-treatment in the two groups.
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24 weeks from the first infusion
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Efficacy: Time to sustained progression of disability
Time Frame: 24 weeks from the first infusion
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Time to sustained progression of disability compared between treatment groups during the first 24 weeks and after cross-over
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24 weeks from the first infusion
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Clanet Michel, MD,PhD, Neurology Department of Purpan Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 12 394 03
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Sclerosis
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University Hospital, Basel, SwitzerlandSwiss National Science FoundationRecruitingMultiple Sclerosis (MS) | Relapsing-remitting Multiple Sclerosis (RRMS) | Secondary-progressive Multiple Sclerosis (SPMS) | Primary Progressive Multiple Sclerosis (PPMS)Switzerland
-
University of California, Los AngelesUnknownRelapsing-remitting Multiple Sclerosis | Secondary-progressive Multiple Sclerosis | Primary-progressive Multiple SclerosisUnited States
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BiogenCompletedMultiple Sclerosis | Relapsing-Remitting Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Multiple Sclerosis, Primary Progressive | Multiple Sclerosis, Remittent ProgressiveJapan
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The Cleveland ClinicUniversity Hospitals Cleveland Medical CenterCompletedRelapsing-Remitting Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Progressive Relapsing Multiple SclerosisUnited States
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University of California, San FranciscoUnited States Department of DefenseRecruitingMultiple Sclerosis, Chronic Progressive | Multiple Sclerosis, Relapsing-Remitting | Multiple Sclerosis (MS) | Multiple Sclerosis Relapse | Multiple Sclerosis, Primary Progressive | Multiple Sclerosis Brain Lesion | Multiple Sclerosis BenignUnited States
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Icahn School of Medicine at Mount SinaiColumbia University; New York Stem Cell Foundation Research InstituteCompletedClinically Isolated Syndrome | Relapsing-Remitting Multiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple SclerosisUnited States
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-
Brigham and Women's HospitalMassachusetts General HospitalRecruitingMultiple Sclerosis | Relapsing Multiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple SclerosisUnited States
-
University of MinnesotaMallinckrodtTerminatedPrimary Progressive Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Progressive Relapsing Multiple SclerosisUnited States
-
Queen Mary University of LondonTakeda Pharmaceuticals International, Inc.RecruitingRelapsing Remitting Multiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple SclerosisUnited Kingdom
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