Autologous Mesenchymal Stem Cells Transplantation for Spinal Cord Injury- A Phase I Clinical Study

June 28, 2016 updated by: National Institute of Blood and Marrow Transplant (NIBMT), Pakistan

Autologous Transplantation of Bone Marrow Mesenchymal Stem Cells in Patients of Spinal Cord Injury-Phase I Clinical Trial

The conventional treatment of spinal cord injury (SCI) includes physical therapy and rehabilitation and in some cases may require surgical intervention. Although improved emergency care and aggressive treatment can help in preventing further damage and even restore minimal sensory functions, still a large proportion of patients suffer with prolonged disabilities. It led neurologists to search out for new treatment options for this otherwise debilitating disorder. Recent advances in research have developed a better understanding of stem cell biology especially their role in tissue repair and regeneration. Encouraging results in pre-clinical phase and limited human trials have proved that stem cells can be safely and effectively delivered to the injured site for regeneration of damaged tissue. Although a variety of cell types have been tried for their role in repair of spinal cord injury, majority of clinical trials employed stem cells taken from bone marrow especially mesenchymal stromal cells (MSC). Bone marrow MSCs are a good choice for regenerative therapies owing to advantages like ease of collection and ex-vivo culturing, immune tolerance and their ability to differentiate into a variety of cell types including neuronal lineage cells. Intravenous application or direct injection of MSCs into cerebrospinal fluid (CSF) via lumber puncture in animal models of SCI and brain trauma had shown that MSCs can migrate towards and integrate into injured spinal tissue and reduce cyst size and increase functional recovery. The literature indicates that acute, sub-acute and chronic injury can be a therapeutic target for MSC grafting. The mechanism of action may however vary among these conditions. In acute phase, MSC administration play anti-inflammatory role, while in sub-acute/chronic setting it may be used as neurostimulator and for cell bridging effect and possibly glial or neuronal cell replacement. The investigators propose a non-randomized, single group, open label, phase-I, interventional study to evaluate the safety and efficacy of intrathecal delivery of patient's own (autologous) bone marrow mesenchymal stem cells for treatment of spinal cord injury. This will include determination of functional recovery (neuro-muscular control and sensation) in the affected area and overall improvement in quality of life of the patients and also take into account any side effects, if observed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The role of regenerative therapies has gained more importance due to increased number of SCI in the wake of recent anti-terrorism operations by the armed forces and non-availability of any curative treatment for this category of patients. The promising results of preliminary clinical trials have proved that adult stem cells especially multipotent mesenchymal stromal cells can be safely injected and well tolerated and have shown functional improvement in SCI patients. The successful treatment in these patients will not only improve functional status of these otherwise debilitating patients, but can also reduce the burden on health care facilities. Mesenchymal stem cells have been shown to promote anatomical and functional recovery in animal models of SCI by promoting tissue sparing, axonal regeneration, and remyelination. Therapeutic effects of MSCs are primarily due to the secretion of soluble factors and the provision of extracellular matrix that provide protection and support repair. MSC are attractive candidates for transplantation into human patients because they can be easily harvested, expanded and banked, or derived directly from the patient allowing for autologous transplantation, obviating the need for immune suppression. In this study patients suffering from sub-acute and chronic phase of spinal cord injury shall be included. Patients will undergo detailed screening through MRI and motor and sensory assessment by ASIA score. Further evaluation will include electromyography (EMG) and tests for electroneurophysiological assessment like nerve conduction velocity (NCV) will also be done. Bone marrow aspiration will be done from iliac crest of the patients, followed by mononuclear cells (MNCs) separation by density gradient centrifugation. MNCs will be washed and cultured in tissue culture flasks. After 48 hours non-adherent cells will be removed from culture. Medium will be changed twice weekly till MSCs reach 70-80 % confluence. At that point MSCs will be harvested and after microbiological and other quality control testing the cellular preparation will be diluted to final concentration and infused by intrathecal injection.

Primary outcome measure is safety which will be determined by clinical evaluation by two independent neurologists during one month of hospital stay after receiving treatment course.

Secondary outcome measures will include American Spinal Injury Association (ASIA) impairment scale and NCV/EMG.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
      • Rawalpindi, Pakistan, 46000
        • Armed Forces Bone Marrow Transplant Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients suffering from sub-acute and chronic phase of spinal cord injury
  • Traumatic spinal cord injury at the thoracic level
  • American Spinal Injury Association (ASIA) impairment scale "A"
  • Confirmation by MRI of injury level
  • Time between injury and enrollment greater than 2 weeks
  • Ability to provide informed consent

Exclusion Criteria:

  • Axonic brain injury
  • Inability to provide consent
  • Open injuries
  • Active infectious diseases
  • Terminal patients
  • Neurodegenerative diseases
  • Evidence of meningitis
  • Cerebral palsy
  • Primary haematologic diseases
  • Coagulopathies
  • Pregnancy
  • Other medical complications that contra-indicate surgery, including major respiratory complications
  • Use of metal implants close to vascular structures (such as cardiac pacemaker or prosthesis) that contraindicate MRI.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Autologous mesenchymal stem cells
use of mesenchymal stem cells as therapeutic intervention for spinal cord injury patients by autologous transplantation
Biological: mesenchymal stem cells
autologous transplantation of mesenchymal stem cells in spinal cord injury patients
Other Names:
  • MSC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of adverse events
Time Frame: 1 month
Number of adverse events occurring in given time frame shall be reported to evaluate overall safety of the procedure
1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensory and motor strength
Time Frame: 1 year
Improvement in sensitivity and motor strength will be measured through change in American Spinal Injury Association (ASIA) score from baseline
1 year
Functional Independence
Time Frame: 1 year
Functional Independence will be measured by FIM scoring
1 year
Muscle strength assessment
Time Frame: 1 year
Shall be done using Frankel scale
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Blood and Marrow Transplant (NIBMT), Pakistan

Collaborators

Armed Forces Institute of Regenerative Medicine

Investigators

  • Principal Investigator: Parvez Ahmed, Commandant Armed Forces Bone Marrow Transplant Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2013

Primary Completion (ACTUAL)

January 1, 2016

Study Completion (ACTUAL)

March 1, 2016

Study Registration Dates

First Submitted

June 18, 2015

First Submitted That Met QC Criteria

June 25, 2015

First Posted (ESTIMATE)

June 26, 2015

Study Record Updates

Last Update Posted (ESTIMATE)

June 29, 2016

Last Update Submitted That Met QC Criteria

June 28, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AFBMTC-SCI-2013

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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