Evaluation of Autologous Mesenchymal Stem Cell Transplantation (Effects and Side Effects) in Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT01377870
• Recruitment Status: Completed
• First Posted: June 21, 2011
• Last Update Posted: March 7, 2018
• Sponsor: Royan Institute
• Information provided by (Responsible Party): Royan Institute

Tracking Information

• First Submitted Date: June 19, 2011
• First Posted Date: June 21, 2011
• Last Update Posted Date: March 7, 2018
• Study Start Date: December 2011
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 20, 2011)

• MRI metrics changes [ Time Frame: 6 months ]
  evaluate the effect of mesenchymal stem cell transplantation on number of GD positive lesions.
• Brain atrophy [ Time Frame: 12 months ]
  evaluate the effect of mesenchymal stem cell transplantation to improve brain atrophy
• number of sever relapses [ Time Frame: 6 months ]
  evaluation the effect of mesenchymal stem cell transplantation on number of sever relapses
• EDSS [ Time Frame: 6 months ]
  Evaluation the effect of mesenchymal stem cells on progression of disease based on EDSS
• MSFC [ Time Frame: 6 months ]
  Evaluation the effect of mesenchymal stem cells transplantation on MSFC

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT01377870 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: June 20, 2011)

• quality of life [ Time Frame: 6 months ]
  Evaluation the effect of mesenchymal stem cell transplantation on patients quality of life
• RAO Test [ Time Frame: 6 months ]
  Evaluation the effect of mesenchymal stem cell transplantation on RAO Test.
• intravenous cell transplantation [ Time Frame: 6 months ]
  evaluation the side effect of intravenous transplantation of mesenchymal stem cell

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Autologous Mesenchymal Stem Cell Transplantation (Effects and Side Effects) in Multiple Sclerosis
• Official Title: Effect and Side Effect of Mesenchymal Stem Cell in Multiple Sclerosis

Brief Summary

Multiple sclerosis is a multifocal inflammatory disease of the central nervous system which affects young individuals and causes paralysis of the limbs, sensation, visual and sphincter problems. The disease is caused by an autoimmune mechanism, ie the immune system produces antibodies and cells which attack the self myelin antigens, causing therefore demyelination. The disease is clinically evident with relapses of neurological disability due to the dysfunction of the areas (plaques of multiple sclerosis) in which damage of myelin occurs. Disability can accumulate with time and the disease enters a progressive phase due to damage of the axons and irreversible neurodegeneration. Although, effective immunotherapies exist which downregulate the autoimmune anti-myelin reactivity and reduce the rate of relapses of MS (like Copaxone and interferons), there is no effective means today to stop the progression of disability and induce rebuilding of the destroyed myelin.Adult bone marrow derived stromal cells (MSC) were shown to induce similar (to the neuronal stem cells) immunomodulatory and neuroregenerative effects and were shown in our laboratory to induce neuroprotection in the animal model of chronic experimental autoimmune encephalomyelitis (EAE). These bone marrow derived MSCs offer practical advantages for clinical therapeutic applications, since they can be obtained from the adult bone marrow and therefore the patient can be the donor for himself, without any danger for rejection of the cells. In addition, MSCs carry a safer profile and are less prone to malignant transformation.

Our center will perform a clinical trial with intra venous transplantation of bone marrow derived mesenchymal stem cell.our purpose is to evaluate the safety and feasibility of cell transplantation after 1year following up.

• Detailed Description: In the clinical trial 30 patients with multiple sclerosis who are drug resistance will take apart.Based on inclusion and exclusion criteria patients are chosen.Bone marrow aspiration will be done for all of them under local anesthesia.Patients are randomly divided in 2 groups:case and control. Then mesenchymal stem cells which are separated and prepared will be transplanted by intravenous injection to the patients in case group and the cells which obtain from patients in control group are frozen and inject after 6 months. Patients will be followed by Evaluation of EDSS MSFC RAO Test brain and cervical MRI and quality of life questionnaire after 1th 3th 6th and 12th months after transplantation.all these tests will be done before transplantation as basic evaluation.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Multiple Sclerosis

Intervention

• Biological: intravenous injection of mesenchymal stem cells
  15 patients with relapsing remitting multiple sclerosis underwent intravenous injection of mesenchymal stem cell
  Other Name: stem cell transplantation
• Biological: injection of cell free media
  Patients who are in control group underwent media injection but after 6 months they will be transplanted by stem cell.
  Other Name: control group

Study Arms

• Placebo Comparator: cell free media
  15 patients with relapsing remitting multiple sclerosis who receive cell free media
  Intervention: Biological: injection of cell free media
• Experimental: mesenchymal stem cell reciepiants
  Patients with relapsing remitting multiple sclerosis who underwent intravenous injection of mesenchymal stem cells
  Intervention: Biological: intravenous injection of mesenchymal stem cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 24, 2014): 22
• Original Estimated Enrollment (submitted: June 20, 2011): 30
• Actual Study Completion Date: April 2014
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Both gender
• Age: 18-55years
• Duration of disease: 2-10 years
• Relapsing remitting with drug resistance
• EDSS: 3-6.5

• Resistance to immunomodulatory and cytotoxic drugs:

  • At least 1-2 sever relapse during 1 year drug treatment
  • At least increase 1 point of EDSS during 1 year drug treatment
• Secondary progressive or relapsing multiple sclerosis
• Primary progressive MS with relapse or GAD positive enhancement
• Secondary progressive MS with relapse
• Secondary progressive MS without relapse:progression of disease with 1 point increase of EDSS during last 18 months

Exclusion Criteria:

• Pregnancy positive test
• Under treatment with cytotoxic drugs at the same time or during last 3 months
• Under treatment with immunomodulatory drugs at the same time or during last month
• Relapse of disease 30 days or less than 30 days before transplantation
• Primary progressive MS with out relapse or GAD positive enhancement

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Iran, Islamic Republic of

Administrative Information

• NCT Number: NCT01377870
• Other Study ID Numbers: Royn-nerve-001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Royan Institute
• Study Sponsor: Royan Institute
• Collaborators: Not Provided

Investigators

• Study Chair: Hamid Gourabi, PhD; head of Royan Institute
• Study Director: Nasser Aghdami, MD,PhD; Head of cell therapy center of Royan Institute
• Principal Investigator: Masoud Nabavi, MD; scientist and clinician
• Principal Investigator: Leila Arab, MD; Department of regenerative medicine,Royan Institute

• PRS Account: Royan Institute
• Verification Date: August 2010