Stem Cells in Rapidly Evolving Active Multiple Sclerosis
Overview
- Phase
- Phase 1
- Intervention
- Mesenchymal stem cells
- Conditions
- Multiple Sclerosis
- Sponsor
- Imperial College London
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Number of Adverse Events Assessed by CTCAE v4.0
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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).
Detailed Description
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 of the patients 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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with clinically and radiologically active multiple sclerosis as defined by:
- •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.
- •Age 18 to 50 years.
- •Disease duration 2 to 10 years from diagnosis (inclusive).
- •Expanded Disability Status Scale (EDSS) 2.0 to 6.5 at screening evaluation.
- •≥ 1 GEL on MRI within 6 months prior to harvesting.
- •Adequate culture of a subject's MSCs and their release for clinical use.
Exclusion Criteria
- •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.
- •SPMS without relapses and without new lesions (GEL or T2 positive) at MRI in the last 18 months.
- •PPMS without positive CSF OCBs or without a GEL or new T2 lesion in the previous 18 months.
- •No gadolinium enhancing lesion(s) in the 3 months prior to bone marrow harvesting.
- •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.
- •Failure of bone marrow (BM) sample to generate MSCs suitable for clinical use within a specified time frame (4 weeks).
- •Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the last 3 months.
- •Treatment with interferon-beta or glatiramer acetate within the last 1 month.
- •Treatment with alemtuzumab (campath-1H) within the last 2 years.
- •Prior treatment with total lymphoid irradiation and autologous or allogeneic hematopoietic stem cell transplantation.
Arms & Interventions
mesenchymal stem cells
1-2 x106 MSCs/kg administered at Week 0
Intervention: Mesenchymal stem cells
Placebo
Suspension media administered at Week 0
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Adverse Events Assessed by CTCAE v4.0
Time Frame: 24 weeks from baseline
The number of adverse events before crossover in the stem cell treatment group compared to the placebo group over the first 24 weeks (please refer to period 1 of the participant flow).
Number of GELs Newly Appearing at Weeks 4, 12 and 24 After MSC Therapy in the First 24 Weeks of Trial
Time Frame: Up to 24 weeks
Where GELs stands for gadolinium enhancing lesions and MSC for Mesenchymal Stem Cell. This was to evaluate the efficacy of autologous mesenchymal stem cells in MS patients, quantified by the reduction in the number of new gadolinium-enhancing lesions counted on MRI scans over 24 weeks and the total number of GELs counted over months 1, 3 and 6 will be compared between treatment groups.
Secondary Outcomes
- Number of Newly Appearing GELs Over Months 1, 3 and 6 Will be Compared Between Treatment Groups.(Months 1, 3 and 6)
- Comparison of Contrast Enhancing Lesions Between Treatment Periods Following Crossover(Months 6-12)
- Combined Unique MRI Activity(Weeks 4, 12 and 24)
- Relapses(6 months)
- Progression of Disability(6 months)