Phase I-II Clinical Trial With Autologous Bone Marrow Derived Mesenchymal Stem Cells for the Therapy of Multiple Sclerosis

NCT02035514 | Completed Phase 1

• 2 other identifiers: CELLTRiMS2010-024081-21
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Immunomodulatory therapies to treat the relapsing-remitting phase of multiple sclerosis (MS) are designed to ameliorate the inflammatory processes that mediate the damage to the central nervous system (CNS) and to delay progression of the disease. To date, there is no effective means to stop the progression of disease and induce remyelination. Adult stem cells therapy show great promise and is rapidly developing as alternative therapeutic strategy. We propose the use of bone marrow-derived autologous Mesenchymal (BM-MSC) Stem Cells transplantation to treat patients with relapsing-remitting MS (RRMS), despite immunomodulatory therapy. Taking advantage of the potential that MSC possess strong immunomodulatory properties thought to play a role in the maintenance of peripheral tolerance and in the control of autoimmunity and that may stimulate repair and regeneration of lesions, we plan a trial of a single injection of autologous BM-MSC into eight patients. First, we aim to assess the feasibility, safety and tolerability of autologous MSC therapy in RRMS. Second, we plan to evaluate the effects of BM-MSC transplantation on MS disease activity by clinical, neurophysiological, immunological and imaging assessments. Autologous MSC will be obtained from bone marrow aspirates, purified by culture and characterized by surface antigen expression. A single dose of autologous BM-MSC will be injected intravenously. Clinical, neurological and immunological assessments will be scheduled at baseline (before BM-MSC transplantation) at 1, 3, and 6 months after transplant. The imaging will be performed at 3 and 6 months after transplant. Proposed trial will enable us to ascertain whether autologous BM-MSC transplantation is a feasible and safe procedure, and whether BM-MSC can establish an environment of immune tolerance and through the local production of neurotrophic/growth factors, might induce neuroprotection and improvement in CNS function.

Conditions

Relapsing Remitting Multiple Sclerosis (RRMS)

Keywords

multiple sclerosis; mesenchymal stem cells; autologous transplantation; MRI efficacy; clinical safety

Outcome Measures

Primary Outcomes (2)

• Change from baseline in safety

  * Physical examination, vital signs (HR, RR, BP, axillary temp), analytical results (biochemistry, hematology,) electrocardiographic monitoring, pulse oximetry and adverse events. * Clinical worsening both new relapses or disability measured by Expanded Disability Status Scale (EDSS), until the end of the study.

  Baseline, month 12

• Change from baseline in effectiveness by MRI

  \- Cumulative number of MRI Gd-enhancing lesions (3 and 6 months post-treatment).

  Baseline, month 6

Secondary Outcomes (14)

• Feasibility

  month 12

• Change from baseline in effectiveness by MRI

  baseline, month 3

• Change in clinical efficacy

  baseline, month 1

• Change in Quality of life

  Baseline, month 6 post-treatment

• Immunology

  baseline, month 6 post-treatment

Study Arms (2)

Arm 1

EXPERIMENTAL

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.

Biological: Bone marrow autologous mesenchymal stem cells transplantation

Arm 2

EXPERIMENTAL

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.

Biological: Bone marrow autologous mesenchymal stem cells transplantation

Interventions

Bone marrow autologous mesenchymal stem cells transplantation BIOLOGICAL

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Relapsing-remitting MS (RRMS) patients
• Age 18-50 years
• Disease duration \>= 2 and \<= 10 years
• EDSS: 3.0 - 6.5
• \) 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Germans Trias i Pujol Hospital: lead
• Ministerio de Sanidad, Servicios Sociales e Igualdad: collaborator

Study Sites (1)

Germans Trias i Pujol Hospital

Badalona, Barcelona, 08916, Spain

Location

Related Publications (1)

• 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.

  PMID: 31072380 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Cristina Ramo, PhD

  Germans Trias i Pujol Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Phase I-II clinical trial with autologous bone marrow derived mesenchymal stem cells for the therapy of mutiple sclerosis.

Study Record Dates

• First Submitted: December 17, 2013
• First Posted: January 14, 2014
• Study Start: December 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: December 15, 2016

Record last verified: 2016-12

Locations

ES (1)