- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02035514
Phase I-II Clinical Trial With Autologous Bone Marrow Derived Mesenchymal Stem Cells for the Therapy of Multiple Sclerosis
Study Overview
Status
Intervention / Treatment
Detailed Description
Multiple sclerosis (MS) is a chronic, demyelinating disease of the CNS. Onset typically occurs in early adulthood. Patients present with intermittent symptoms that are partially reversible; this form is termed relapsing-remitting (RRMS). Over time, most patients develop secondary-progressive MS (SPMS) which manifests as irreversible and gradual neurological impairments that often progress without acute relapses. Beta-interferons or glatiramer acetate represents the first line therapeutic option for RRMS. Clinical trials confirm that show partial efficacy, though they do not prevent the onset of secondary progression. SPMS, is the consequence of axonal loss and neurodegeneration and no current therapy has been effective. Stem cell therapy show great promise and is rapidly developing as alternative therapeutic strategy. Clinical indications for adult stem cells, which can be safely harvested and normally behave well without formation of tumours, are rapidly increasing. The majority of human stem cell trials have focused on clinical applications for haematopoietic stem cells (HSC), mesenchymal stem cells (MSC), or both, which can be easily obtained in clinically sufficient numbers from peripheral blood, bone marrow, adipose tissue, or umbilical cord blood and placenta. MSC can readily be isolated from a small sample of bone marrow and rapidly expanded so as to generate large numbers of cells for autologous therapies. When administered intravenously have an immune suppressive effect that can ameliorate animal autoimmune diseases. MSC transplantation significantly improves clinical outcome in experimental allergic encephalitis (EAE), the animal model of MS. When intravenously injected, MSC may migrate to inflammatory brain lesions and promote survival of brain-resident cells. Several disease models demonstrate axonal neuroprotection following MSC therapy, with some evidence that this is potentially mediated through the production of neurotrophic/growth factors, and/or immunomodulatory effects of MSC. For that reasons, MSC have become the focus of research as a potential cell therapy for inducing neuroprotection in human neurodegenerative diseases such as MS.
A growing body of literature confirms the therapeutic MSC biological properties, and provide a plausible mechanism of action to guide clinical trial design with a number of phase I/II trials in MS patients now underway. Experimental clinical trials in MS are being considered or have recently been initiated by several research groups, which are testing the therapeutic potential of different sources of MSC. Learning from previous clinical studies, and taking advantage of the potential that adult BM-MSC may stimulate repair and remyelination, to plan a clinical trial in patients with inflammatory MS seems reasonable. We propose a safety trial of a single intravenous injection of autologous bone marrow-derived MSC into 8 subjects with RRMS. The trial proposed here will enable us to ascertain whether autologous BM-MSC transplantation is a safe procedure, and whether BM-MSC therapy during the relapsing-remitting phase of MS can establish a immunomodulatory and regenerative microenvironment and reverse neurological disability in RRMS patients.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
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Barcelona
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Badalona, Barcelona, Spain, 08916
- Germans Trias I Pujol Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Relapsing-remitting MS (RRMS) patients
- Age 18-50 years
- Disease duration >= 2 and <= 10 years
- EDSS: 3.0 - 6.5
1) Patients who do not wish to be subjected to approved immunomodulatory treatments (interferon beta and acetato de glatiramer) 2) Patients who have tried and had to withdraw within a year due to adverse events 3) Patients who have not responded to them after at least 1 year of continuous treatment. Lack of response is considered one or more of the following
- >= 1 moderate-severe relapses in past 12 months
- >= 2 moderate-severe relapses in past 24 months
- >= 1 Gadolinium enhancing lesions in a MRI performed in previous 12 months
Relapse:
- Mild: Increase of < 1 EDSS point
- Moderate: Increase of >= 1 EDSS point (if baseline EDSS 3.0-5.0) or 0.5 EDSS points (if baseline EDSS >= 5.5)
- Severe: Increase of >=3 EDSS point
- Social, mental and physical ability to communicate with physicians and to understand the requirements of the protocol
- Has given informed consent to participate in the study
Exclusion Criteria:
- RRMS not fulfilling inclusion criteria
- SPMS or PPMSTreatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization
- Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization
- Treatment with interferon-beta or glatiramer acetate within the 30 days prior to randomization
- Treatment with corticosteroids within the 30 days prior to randomization
- Relapse occurred during the 60 days prior to randomization
- History of cancer or clinical or laboratory results indicative of severe systemic diseases, including infection for HIV, Hepatitis B or C
- Pregnancy or risk of pregnancy/ lactation
- Current treatment with an investigational therapy
- Inability to give written informed consent in accordance with research ethics board guidelines
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Arm 1
A single infusion of up to 1 million cells per Kg of autologous MSC stem cells vs placebo.
The treatment will be on day 0 and placebo on month 6.
|
|
EXPERIMENTAL: Arm 2
A single infusion of up to 1 million cells per Kg of autologous MSC stem cells vs placebo.
The treatment will be on month 6 and placebo on day 0.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from baseline in safety
Time Frame: Baseline, month 12
|
|
Baseline, month 12
|
Change from baseline in effectiveness by MRI
Time Frame: Baseline, month 6
|
- Cumulative number of MRI Gd-enhancing lesions (3 and 6 months post-treatment).
|
Baseline, month 6
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Feasibility
Time Frame: month 12
|
- Availability of a viable product that allows the treatment, checking whether the procedures can be performed as indicated in protocol.
|
month 12
|
Change from baseline in effectiveness by MRI
Time Frame: baseline, month 3
|
- Cumulative number of lesions visualized on T2 sequence (3 and 6 months post-treatment).
|
baseline, month 3
|
Change in clinical efficacy
Time Frame: baseline, month 1
|
|
baseline, month 1
|
Change in Quality of life
Time Frame: Baseline, month 6 post-treatment
|
- Multiple Sclerosis Quality of Life (MSQOL-54)
|
Baseline, month 6 post-treatment
|
Immunology
Time Frame: baseline, month 6 post-treatment
|
|
baseline, month 6 post-treatment
|
Axonal effect
Time Frame: baseline, month 6
|
- Optical coherence tomography (OCT)
|
baseline, month 6
|
Change from baseline in effectiveness by MRI
Time Frame: baseline, month 6
|
- Cumulative number of lesions visualized on T2 sequence (3 and 6 months post-treatment).
|
baseline, month 6
|
Change in clinical efficacy
Time Frame: baseline, month 3
|
|
baseline, month 3
|
Change in clinical efficacy
Time Frame: baseline, month 6 post-treatment
|
|
baseline, month 6 post-treatment
|
Change in Quality of life
Time Frame: baseline, month 1
|
- MSQOL-54
|
baseline, month 1
|
Change in Quality of life
Time Frame: baseline, month 3
|
- MSQOL-54
|
baseline, month 3
|
Immunology
Time Frame: baseline, month 1
|
|
baseline, month 1
|
Immunology
Time Frame: baseline, month 3
|
|
baseline, month 3
|
Axonal effect
Time Frame: baseline, month 12 post-treatment
|
- OCT
|
baseline, month 12 post-treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Cristina Ramo, PhD, Germans Trias i Pujol University Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CELLTRiMS
- 2010-024081-21 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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