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MEsenchymal StEm Cells for Multiple Sclerosis (MESEMS)

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ClinicalTrials.gov Identifier: NCT01854957
Recruitment Status : Unknown
Verified May 2013 by Antonio Uccelli, University of Genova.
Recruitment status was:  Recruiting
First Posted : May 16, 2013
Last Update Posted : May 16, 2013
Sponsor:
Collaborators:
Azienda Ospedaliera Universitaria Integrata Verona
Ospedale San Raffaele
Information provided by (Responsible Party):
Antonio Uccelli, University of Genova

Tracking Information
First Submitted Date  ICMJE May 8, 2013
First Posted Date  ICMJE May 16, 2013
Last Update Posted Date May 16, 2013
Study Start Date  ICMJE July 2012
Estimated Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 13, 2013)
  • Safety [ Time Frame: 24 weeks from the first infusion ]
    Incidence and severity of adverse events in MSC treatment group compared to placebo group.
  • efficacy [ Time Frame: 24 weeks from the first infusion ]
    total number of contrast-enhancing lesions (GEL) at MRI scan
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2013)
  • Efficacy [ Time Frame: 48 weeks from the first infusion ]
    Number of GEL counted over week 28, 36 and 48 compared with the number of GEL counted over 4, 12 and 24 weeks.
  • Efficacy [ Time Frame: 24 weeks form the first infusion ]
    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 [ Time Frame: 48 weeks from the first infusion ]
    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 [ Time Frame: 48 weeks from the first infusion ]
    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 Frame: 48 weeks from the first infusion ]
    Time to sustained progression of disability and proportion of progression-free patients compared between treatment groups during the first 24 weeks and after cross-over
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MEsenchymal StEm Cells for Multiple Sclerosis
Official Title  ICMJE MEsenchymal StEm Cells for Multiple Sclerosis (MESEMS) Phase I-II Clinical Trial With Autologous Mesenchymal Stem Cells (MSCs) for the Therapy of Multiple Sclerosis
Brief Summary A double-blind, randomized, cross-over phase I/II study to evaluate the safety and the efficacy of the intravenous administration of autologous Mesenchymal Stem Cells (MSC) to patients with active multiple sclerosis (MS) resistant to currently available therapies.
Detailed Description

The mechanism of action of MSC relies on their ability to modulate pathogenic immune responses and provide neuroprotection through the release of anti-apoptotic, anti-oxidant and trophic factors as demonstrated by in vitro and in vivo preclinical studies.

Patients will be randomized to receive immediate vs. delayed treatment with either a dose equal to 1-2 millions/kg of body weight of autologous MSC, or equivalent volume of suspension media at baseline. At 6 months treatments will be reversed.

The primary outcome of this study is to evaluate

  • treatment's safety within one year from MSC administration by measuring the the number, time-frame and severity of adverse event and
  • treatment's activity in terms of reduction in the total number of contrast-gadolinium enhancing lesions (GEL) by magnetic resonance imaging (MRI) scans.

Secondary outcomes are to gain preliminary information on the efficacy of the experimental treatment in terms of combined MRI activity and clinical efficacy (incidence of relapses and disability progression).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE Biological: Autologous Mesenchymal Stem Cells
Single dose of 1-2 x 1000000 cells/Kg body weight
Study Arms  ICMJE
  • Experimental: Autologous 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
    Intervention: Biological: Autologous Mesenchymal Stem Cells
  • 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
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 13, 2013)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2014
Estimated Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

- 1. Diagnosis of MS

a. 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: i. ≥1 clinically documented relapse in past 12 months

ii. ≥2 clinically documented relapses in last 24 months

iii. ≥1 GEL at MRI performed within the last 12 months

b. 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:

i. an increase of ≥1 point of the expanded disability status scale (EDSS) (if at randomization EDSS ≤ 5.0) or 0.5 EDSS point (if at randomization EDSS ≥ 5.5) in the last 12 months

ii. ≥1 clinically documented relapse or ≥ 1 GEL at MRI within the last twelve months.

c. Primary progressive MS (PPMS) patients with all the following features:

i. an increase of ≥1 EDSS point (if at randomization EDSS ≤ 5.0) or 0.5 EDSS point (if at randomization EDSS ≥5.5), in the last twelve months

ii. ≥ 1 GEL at MRI performed within the last 12 months

iii. positive cerebrospinal fluid (CSF) (oligoclonal banding

  • 2. Age 18 to 50 years
  • 3. Disease duration 2 to 10 years (included)
  • 4. EDSS 3.0 to 6.5

Exclusion Criteria:

  • 1. RRMS not fulfilling inclusion criteria
  • 2. SPMS not fulfilling inclusion criteria
  • 3. PPMS not fulfilling inclusion criteria
  • 4. Any active or chronic infection including infection with HIV1-2 or chronic Hepatitis B or Hepatitis C
  • 5. Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization
  • 6. Treatment with interferon-beta or glatiramer acetate within the 30 days prior to randomization
  • 7. Treatment with corticosteroids within the 30 days prior to randomization
  • 8. Relapse occurred during the 60 days prior to randomization
  • 9. 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
  • 10. Severely limited life expectancy by another co-morbid illness
  • 11. History of previous diagnosis of myelodysplasia or previous hematologic disease or current clinically relevant abnormalities of white blood cell counts
  • 12. Pregnancy or risk or pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study)
  • 13. eGFR < 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination.
  • 14. Inability to give written informed consent in accordance with research ethics board guidelines
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01854957
Other Study ID Numbers  ICMJE MESEMS
2011-001295-19 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Antonio Uccelli, University of Genova
Study Sponsor  ICMJE Antonio Uccelli
Collaborators  ICMJE
  • Azienda Ospedaliera Universitaria Integrata Verona
  • Ospedale San Raffaele
Investigators  ICMJE
Principal Investigator: Giancarlo Comi, MD Ospedale San Raffaele
Principal Investigator: Bruno Bonetti, MD Azienda Ospedaliera Universitaria Integrata di Verona
PRS Account University of Genova
Verification Date May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP