Back to resultsMEsenchymal StEm Cells for Multiple Sclerosis (MESEMS)
Primary Purpose
Multiple Sclerosis
Status
Terminated
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Mesenchymal stem cells
Suspension media
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring Multiple Sclerosis, Bone-marrow, Stem cells, Cell therapy
Eligibility Criteria
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.
Sites / Locations
- Purpan Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Mesenchymal stem cells
Suspension media
Arm Description
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
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
Outcomes
Primary Outcome Measures
Safety of MSCs infusion, number, timeframe of occurrence and severity of Adverse Events
Safety assessed by number, timeframe of occurrence and severity of Adverse Events
efficacy: number of contrast-enhancing lesions (GEL) at MRI scan
total number of contrast-enhancing lesions (GEL) at MRI scan
Secondary Outcome Measures
Efficacy of the experimental treatment in term of combined MRI activity
Number of GEL counted over week 28, 36 and 48 compared with the number of GEL counted over 4, 12 and 24 weeks.
Efficacy assessed by combined unique MRI activity, volume of GEL, and volume of BH
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.
Efficacy assessed by combined unique MRI activity, volume of GEL and volume of BH
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.
Efficacy: Number of relapses
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.
Efficacy: Time to sustained progression of disability
Time to sustained progression of disability compared between treatment groups during the first 24 weeks and after cross-over
Full Information
NCT ID
NCT02403947
First Posted
March 9, 2015
Last Updated
November 29, 2018
Sponsor
University Hospital, Toulouse
1. Study Identification
Unique Protocol Identification Number
NCT02403947
Brief Title
MEsenchymal StEm Cells for Multiple Sclerosis
Acronym
MESEMS
Official Title
Treatment of Multiple Sclerosis With Mesenchymal Stem Cells: Phase I/II Study
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Terminated
Why Stopped
inclusion default
Study Start Date
February 2015 (undefined)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
December 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
MSCs have the remarkable ability to modulate the immune response mainly by inhibiting proliferation of T cells and to protect injured tissues through paracrine mechanisms. There is an urgent need to evaluate the real efficacy of MSC transplantation, and its possible position in the current therapeutic armamentarium. An international panel of MS neurology and stem cell experts, as well as immunologists formed an "International Mesenchymal Stem Cells Transplantation" (MSCT) Study Group with the aim to derive a consensus on what cells should be used for transplantation and develop a treatment protocol and an experimental program that will eventually attest to the efficacy of MSC transplantation and understand the mechanism that underlie the benefit. 12 patients with MS will be treated with IV injections of autologous isolated and expanded mesenchymal stem cells. Clinical and objective evaluations will be performed at baseline and during 12 months follow-up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Multiple Sclerosis, Bone-marrow, Stem cells, Cell therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mesenchymal stem cells
Arm Type
Experimental
Arm Description
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
Arm Title
Suspension media
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Mesenchymal stem cells
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Suspension media
Intervention Description
injection suspension media
Primary Outcome Measure Information:
Title
Safety of MSCs infusion, number, timeframe of occurrence and severity of Adverse Events
Description
Safety assessed by number, timeframe of occurrence and severity of Adverse Events
Time Frame
24 weeks from the first infusion
Title
efficacy: number of contrast-enhancing lesions (GEL) at MRI scan
Description
total number of contrast-enhancing lesions (GEL) at MRI scan
Time Frame
24 weeks from the first infusion
Secondary Outcome Measure Information:
Title
Efficacy of the experimental treatment in term of combined MRI activity
Description
Number of GEL counted over week 28, 36 and 48 compared with the number of GEL counted over 4, 12 and 24 weeks.
Time Frame
48 weeks from the first infusion
Title
Efficacy assessed by combined unique MRI activity, volume of GEL, and volume of BH
Description
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.
Time Frame
24 weeks from the first infusion
Title
Efficacy assessed by combined unique MRI activity, volume of GEL and volume of BH
Description
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.
Time Frame
48 weeks from the first infusion
Title
Efficacy: Number of relapses
Description
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.
Time Frame
24 weeks from the first infusion
Title
Efficacy: Time to sustained progression of disability
Description
Time to sustained progression of disability compared between treatment groups during the first 24 weeks and after cross-over
Time Frame
24 weeks from the first infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clanet Michel, MD,PhD
Organizational Affiliation
Neurology Department of Purpan Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Purpan Hospital
City
Toulouse
ZIP/Postal Code
31059
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
31072380
Citation
Uccelli A, Laroni A, Brundin L, Clanet M, Fernandez O, Nabavi SM, Muraro PA, Oliveri RS, Radue EW, Sellner J, Soelberg Sorensen P, Sormani MP, Wuerfel JT, Battaglia MA, Freedman MS; MESEMS study group. MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis. Trials. 2019 May 9;20(1):263. doi: 10.1186/s13063-019-3346-z.
Results Reference
derived
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MEsenchymal StEm Cells for Multiple Sclerosis
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