Clinical trial NCT02403947: MEsenchymal StEm Cells for Multiple Sclerosis
Official title: Treatment of Multiple Sclerosis With Mesenchymal Stem Cells: Phase I/II Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Bone-marrow
Stem cells
Cell therapy
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2015-03-31
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety of MSCs infusion, number, timeframe of occurrence and severity of Adverse Events
timeFrame: 24 weeks from the first infusion
measure: efficacy: number of contrast-enhancing lesions (GEL) at MRI scan
timeFrame: 24 weeks from the first infusion
Secondary outcomes:
measure: Efficacy of the experimental treatment in term of combined MRI activity
timeFrame: 48 weeks from the first infusion
measure: Efficacy assessed by combined unique MRI activity, volume of GEL, and volume of BH
timeFrame: 24 weeks from the first infusion
measure: Efficacy assessed by combined unique MRI activity, volume of GEL and volume of BH
timeFrame: 48 weeks from the first infusion
measure: Efficacy: Number of relapses
timeFrame: 24 weeks from the first infusion
measure: Efficacy: Time to sustained progression of disability
timeFrame: 24 weeks from the first infusion
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Purpan Hospital
Study officials:
affiliation: Neurology Department of Purpan Hospital
name: Clanet Michel, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.