MEsenchymal StEm Cells for Multiple Sclerosis (MESEMS)

This study is currently recruiting participants.
Verified May 2013 by University of Genova
Sponsor:
Collaborators:
Azienda Ospedaliera Universitaria Integrata Verona
Ospedale San Raffaele
Information provided by (Responsible Party):
Antonio Uccelli, University of Genova
ClinicalTrials.gov Identifier:
NCT01854957
First received: May 8, 2013
Last updated: May 13, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Biological: Autologous Mesenchymal Stem Cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: MEsenchymal StEm Cells for Multiple Sclerosis (MESEMS) Phase I-II Clinical Trial With Autologous Mesenchymal Stem Cells (MSCs) for the Therapy of Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by University of Genova:

Primary Outcome Measures:
  • Safety [ Time Frame: 24 weeks from the first infusion ] [ Designated as safety issue: Yes ]
    Incidence and severity of adverse events in MSC treatment group compared to placebo group.

  • efficacy [ Time Frame: 24 weeks from the first infusion ] [ Designated as safety issue: No ]
    total number of contrast-enhancing lesions (GEL) at MRI scan


Secondary Outcome Measures:
  • Efficacy [ Time Frame: 48 weeks from the first infusion ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 20
Study Start Date: July 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Biological: Autologous Mesenchymal Stem Cells
Single dose of 1-2 x 1000000 cells/Kg body weight
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

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).

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01854957

Contacts
Contact: Antonio Uccelli, MD +390103537028 MESEMS@unige.it

Locations
Italy
University of Genova Recruiting
Genova, Italy, 16132
Principal Investigator: Antonio Uccelli, MD, PhD         
Sponsors and Collaborators
Antonio Uccelli
Azienda Ospedaliera Universitaria Integrata Verona
Ospedale San Raffaele
Investigators
Principal Investigator: Giancarlo Comi, MD Ospedale San Raffaele
Principal Investigator: Bruno Bonetti, MD Azienda Ospedaliera Universitaria Integrata di Verona
  More Information

No publications provided

Responsible Party: Antonio Uccelli, MD, University of Genova
ClinicalTrials.gov Identifier: NCT01854957     History of Changes
Other Study ID Numbers: MESEMS, 2011-001295-19
Study First Received: May 8, 2013
Last Updated: May 13, 2013
Health Authority: Italy: National Institute of Health

Keywords provided by University of Genova:
Multiple sclerosis
Mesenchymal stem cells

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 17, 2014