Stem Cells in Rapidly Evolving Active Multiple Sclerosis (STREAMS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01606215
First received: May 21, 2012
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

This is a randomised, double-blind crossover study to study the effect of intravenous treatment with autologous (derived from the individuals themselves) mesenchymal stem cells (MSCs)in patients with multiple sclerosis (MS).

Current treatments for MS target the immune system and are not curative. There is much interest in MSCs as they have the potential to not only affect the immune system but may also promote repair. This study will use MSCs that are harvested from the bone marrow and grown for up to 52 days before being given back to the person from whom they were harvested. This avoids any chemotherapy so is therefore safer than other types of stem cells. In this crossover study, everyone will receive their own stem cells back but in half it will be delayed by 24 weeks.

The primary outcomes are to check that the procedure is safe and to measure any changes on the MRI at 24 weeks. Other more exploratory measures will try to assess effects on repair in the central nervous system (CNS).


Condition Intervention Phase
Multiple Sclerosis
Drug: Mesenchymal stem cells
Drug: Placebo
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: Stem Cells in Rapidly Evolving Active Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Safety [ Time Frame: Up to 1 year from baseline ] [ Designated as safety issue: Yes ]
    The number,time-frame and severity of adverse events in the stem cell treatment group will be compared to the placebo group.

  • Efficacy [ Time Frame: Up to 1 year from baseline ] [ Designated as safety issue: No ]
    To evaluate the efficacy of autologous mesenchymal stem cells in MS patients, quantified by the reduction in the number of new contrast-enhancing lesions on MRI scans over 24 weeks and the total number of GEL counted over months 1, 3 and 6 will be compared between treatment groups.


Secondary Outcome Measures:
  • contrast enhancing lesions identified over months 1, 3 and 6 will be compared between treatment groups. [ Time Frame: Months 1, 3 and 6 ] [ Designated as safety issue: No ]
    Number of contrast enhancing lesions identified over months 1, 3 and 6 will be compared between treatment groups.

  • Comparison of contrast enhancing lesions between treatment periods [ Time Frame: Months 1-12 ] [ Designated as safety issue: No ]
    The number of contrast enhancing lesions counted over months 7, 9 and 12 (cross-over re-treatment) compared between treatment periods (placebo vs. active treatment) for each patient.

  • Combined unique MRI activity [ Time Frame: Months 1-12 ] [ Designated as safety issue: No ]
    The number of new or enlarging T2, or enhancing or re-enhancing lesions.

  • Relapses [ Time Frame: 20 months ] [ Designated as safety issue: No ]
    number of relapses in MSC treatment group vs. placebo group in the first 6 months and after cross-over re-treatment in the two groups

  • Progression of disability [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    time to sustained progression of disability and proportion of progression-free patients.

  • Disease free patients [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    The proportion of disease-free patients (i.e. patients without relapses) and progression of MRI activity in the two groups.

  • MSFC score [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    the changes in the Multiple Sclerosis Functional Composite (MSFC) score in MSC treatment group compared to the placebo group.

  • peripheral immune responses [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Type 4 hypersensitivity reaction [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    The effect of mesenchymal stem cells on delayed type hypersensitivity (Type 4 hypersensitivity reaction) as measured by the Mantoux test


Estimated Enrollment: 13
Study Start Date: January 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: mesenchymal stem cells Drug: Mesenchymal stem cells
1.0-2.0 million cells/kg body weight
Sham Comparator: Placebo Drug: Placebo
Placebo

  Eligibility

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

Inclusion Criteria:

Patients with clinically and radiologically active multiple sclerosis as defined by:

  1. Diagnosis of MS:

    • Relapsing remitting MS (RRMS): ≥ 1 moderate-severe relapse and ≥1 GEL in past 18 months or ≥ 1 moderate-severe relapse and ≥1 new T2 lesion in past 18 months.
    • Secondary progressive MS (SPMS) with an increase of ≥ 1 EDSS point (if baseline EDSS ≤ 5) or 0.5 EDSS point (if baseline EDSS ≥ 5.5), in the previous 18 months and ≥ 1 GEL in past 18 months or ≥ 1 moderate-severe relapse and ≥1 new T2 lesion in past 18 months.
    • Primary progressive MS (PPMS) patients with positive oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) and an increase of ≥ 1 EDSS point (if baseline EDSS is ≤ 5.0) or 0.5 EDSS point (if baseline EDSS is ≥ 5.5), or quantifiable, objective evidence of equivalent progression in the previous 18 months and ≥ 1 GEL in past 18 months or ≥ 1 new T2 lesion in past 18 months.
  2. Age 18 to 50 years.
  3. Disease duration 2 to 10 years from diagnosis (inclusive).
  4. Expanded Disability Status Scale (EDSS) 3.0 to 6.5 at screening evaluation.
  5. ≥ 1 GEL on MRI within 6 months prior to harvesting.
  6. Adequate culture of a subject's MSCs and their release for clinical use.

Exclusion Criteria:

  1. RRMS without at least one severe relapse in the previous 18 months or without at least one GEL or one new T2 in the previous 18 months.
  2. SPMS without relapses and without new lesions (GEL or T2 positive) at MRI in the last 18 months.
  3. PPMS without positive CSF OCBs or without a GEL or new T2 lesion in the previous 18 months.
  4. No gadolinium enhancing lesion(s) in the 3 months prior to bone marrow harvesting.
  5. A previously ineligible patient who failed to meet the MRI requirements of the inclusion criteria will not be reviewed again even if further imaging, revealing ≥ 1 GEL, becomes available.
  6. Failure of bone marrow (BM) sample to generate MSCs suitable for clinical use within a specified time frame (4 weeks).
  7. Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the last 3 months.
  8. Treatment with interferon-beta or glatiramer acetate within the last 1 month.
  9. Treatment with alemtuzumab (campath-1H) within the last 2 years.
  10. Prior treatment with total lymphoid irradiation and autologous or allogeneic hematopoietic stem cell transplantation.
  11. Participation in clinical trials of any experimental drugs in the 6 months before study entry.
  12. Corticosteroid treatment in the last 30 days.
  13. Presence of any active or chronic infection.
  14. Previous history of a malignancy other than basal cell carcinoma of the skin and carcinoma in situ that has been in remission for more than one year.
  15. Severely limited life expectancy by any other co-morbid illness.
  16. Abnormal blood counts, a history of myelodysplasia or other cytopenia.
  17. Known pregnancy, positive urine pregnancy test at screening or risk or pregnancy (this includes patients who are unwilling to practice active contraception during the duration of the study).
  18. Contraindication to MRI including but not limited to intracranial aneurysm clips (except Sugita), history of intra-orbital metal fragments that have not been removed by an MD (as confirmed by orbital X-Ray), pacemaker and non-MRI compatible devices (e.g. heart valves, inner ear implants), history of claustrophobia or the inability of the subject to lie still on their back for a period of 1.5 hours in the MRI scanner.
  19. An estimated glomerular filtration rate (eGFR)< 60 mL/min/1.73m2 or history or presence of renal impairment (e.g. serum creatinine clearance less than 30ml/min).
  20. Inability to give written informed consent/comply with study procedures.
  21. Any significant organ dysfunction or co-morbidity that the Investigators consider would put the subject at unacceptable risk by participating in the study or that would interfere with the functional assessments.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01606215

Locations
United Kingdom
Imperial College Healthcare NHS Trust
London, United Kingdom, W12 0NN
Sponsors and Collaborators
Imperial College London
Investigators
Principal Investigator: Paolo A Muraro, MD PhD Imperial College London
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01606215     History of Changes
Other Study ID Numbers: CRO1959
Study First Received: May 21, 2012
Last Updated: April 30, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: National Institute for Health Research
United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
multiple sclerosis
mesenchymal stem cells
bone marrow
rapidly evolving

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

ClinicalTrials.gov processed this record on October 19, 2014