Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells
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|ClinicalTrials.gov Identifier: NCT01575470|
Recruitment Status : Completed
First Posted : April 11, 2012
Last Update Posted : July 13, 2016
The purpose of this study is to determine if bone marrow harvest, BMMNC separation, and re-infusion in adults with acute severe TBI is safe and will improve functional outcome.
12/09/2015 Update: The study is closed to new enrollment and all follow-up visits have been completed. Data analysis is underway.
|Condition or disease||Intervention/treatment||Phase|
|Traumatic Brain Injury||Biological: autologous bone marrow mononuclear cells||Phase 1 Phase 2|
Traumatic brain injury (TBI) contributes to 50% of all trauma deaths. The mortality rate for adults following severe TBI (Glasgow Coma Scale < 9) is estimated to be 33%. There is currently no therapy to reverse the primary injury associated with TBI. Over the past 10 years there has been a growing body of literature supporting the use of various progenitor cell types to treat acute neurological injuries such as TBI and stroke. Neural stem cells (adult and embryonic), mesenchymal stromal and multipotent adult progenitor cells, and bone marrow mononuclear cells (from which MSC and MAPCs are derived) have all shown efficacy in pre-clinical models of TBI/stroke through various mechanisms; however, few groups believe that true neural replacement and integration are the putative mechanisms involved in the observed efficacy. More likely is that the progenitor cell populations are modifying the regional response to injury (inflammatory/reparative vs. regenerative), resulting in improved functional outcomes. Our primary hypothesis is that bone marrow mononuclear cell (BMMNC) autologous transplantation after TBI is safe (harvest and infusion related toxicity) after TBI. Our secondary hypothesis is that functional outcomes measures will improve after BMMNC infusion, (3) BMMNC infusion will reduce BBB permeability, (4) BMMNC is neuroprotective and preserves grey matter and white matter volumes after TBI.
Patients, ages18 to 55 years old, admitted to Memorial Hermann Hospital Trauma Center with Glasgow Coma Scores (GCS) of 5 to 8 will be screened. Those patients meeting inclusion/exclusion criteria (or their Legal Authorized Representative [LAR]) will be offered consent to participate. This is a dose-escalation study consisting of 4 cohorts including a control group (5 subjects/cohort). The first five subjects will not undergo the bone marrow harvest procedure; though they will be followed and treated the same as the other study participants and complete all follow-up procedures. Subjects 6-10 will receive the lowest dose target of 6X106 mononuclear cells/kilogram body weight. Subjects 11-15 will receive 9x106 mononuclear cells/kilogram body weight, and lastly Subjects 16-20 will receive 12X106 mononuclear cells/kilogram body weight. The study is NOT powered to detect functional measures of efficacy. However, estimates can be made regarding potential treatment effect sizes to allow rational power analyses for the follow-on Phase II study. This study should determine if bone marrow harvest, BMMNC separation, and reinfusion is safe in adults with acute, severe TBI.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells|
|Study Start Date :||March 2012|
|Actual Primary Completion Date :||May 2015|
|Actual Study Completion Date :||May 2015|
Experimental: bone marrow mononuclear cells
a bone marrow harvest will be performed within 36 hours of injury followed by a single intravenous infusion of autologous bone marrow mononuclear cells (BMMNCs)
Biological: autologous bone marrow mononuclear cells
bone marrow harvest (5ml/kg of body weight) performed within 36 hours of injury, followed by single intravenous infusion of bone marrow mononuclear cells.
Other Name: BMMNCs
- neurological events (seizures, changes in Glasgow coma score [GCS], cerebral vascular accident [CVA}) [ Time Frame: 12 hours post product infusion up to 21 days post infusion ]
- infectious morbidity [ Time Frame: up to 21 days post infusion ]
- global functional status per the GOS-E [ Time Frame: up to 6 months post injury/treatment ]the Glasgow Outcome Scale-Extended (GOS-E) will be administered to assess global functional status (consciousness, independence, work status, return of lifestyle)
- global functioning per the Disability Rating Scale [ Time Frame: up to 6 months post injury/treatment ]the Disability Rating Scale (DRS) will be administered which measures level of arousal, cognitive ability related to activities of daily living, motor response, feeding, toileting, grooming and employability
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01575470
|United States, Texas|
|The University of Texas Health Science Center at Houston|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Charles S Cox, Jr., M.D.||The University of Texas Health Science Center, Houston|