Autologous Bone Marrow Mononuclear Cell Administration for Lower Extremity Compartment Syndrome Injury
Overview
- Phase
- Phase 1
- Intervention
- Intramuscular administration of autologous BM-MNCs
- Conditions
- Compartment Syndrome Traumatic Lower Extremity
- Sponsor
- Oregon Health and Science University
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Efficacy as determined by muscle strength
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a phase 1 study to assess safety and tolerability of intramuscular administration of two different doses of autologous bone marrow mononuclear cells (BM-MNCs) for treatment of lower extremity injury complicated by compartment syndrome injury.
Detailed Description
The primary objectives are to assess safety and tolerability of a high and low dose of autologous bone marrow mononuclear cells. Secondary objectives include evaluation of potential responses of the BM-MNC therapy. This is a two-stage, randomized, unblinded, multicenter (two sites), controlled phase 1 clinical trial to evaluate the safety of two different doses of intramuscular injections of autologous bone marrow mononuclear cells, commonly known as a type of stem cell. Acute compartment syndrome injury is a mixed soft tissue injury due to a trauma that causes edema leading to excessive pressure in the muscle compartment. This type of injury frequently results in permanent reduction in function and disability. A total of 18 participants that have undergone a fasciotomy for treatment of a lower leg compartment syndrome will be enrolled with 6 assigned to the control (observational) group, 6 to the low cell-dose group and 6 to the high cell-dose group. The treatment arm will receive a single dose (high or low) of autologous BM-MNCs 5 - 9 days post injury and fasciotomy and a minimum of 3 months of standard of care physical rehabilitation. An observational control arm will not receive cells post fasciotomy but will undergo a standard of care course of physical therapy and will be followed for comparison to assess early safety signals and potential benefit.
Investigators
Kenton W. Gregory
Director, Oregon Center for Regenerative Medicine
Oregon Health and Science University
Eligibility Criteria
Inclusion Criteria
- •Females and males 18 - 70 years old
- •Has single or multiple compartment syndrome of the lower leg that includes the anterior tibial compartment
- •Trauma patients with lower extremity CS requiring fasciotomy that can be treated with autologous BM-MNC therapy on day 5-9 post-fasciotomy
- •Ability to sign an informed patient consent form
- •Access and willingness to complete a standard of care course of rehabilitation therapy and 24 months follow-up evaluations
- •Ability to close the fasciotomy wound per physician assessment
- •Anterior compartment muscle volume between 100 - 280 cc as determined by MRI/CT
- •Within the institutions' clinical reference ranges for HbA1C
- •Negative HIV test
- •· - Non-fracture, closed fracture or compound fracture type I (wound less than 1cm \& compound from within out) (Gustilo-Anderson classification)
Exclusion Criteria
- •Prior compartment syndrome of same limb;
- •Active malignancy or has undergone treatment for a malignancy in the preceding 5 years as indicated in past medical history or self-report if medical records do not accompany subject or are unable to be collected (basal cell carcinoma non-exclusionary);
- •HIV positive as indicated by past medical history, self-report, or positive HIV test;
- •Diagnosis of Type 1 or Type 2 diabetes with elevated HbA1C consistent with diabetes;(controlled diabetes acceptable, diabetes medication for other diagnosis acceptable)
- •Diagnosis of chronic lower extremity vascular disease as diagnosed by current physician diagnosis, indicated in past medical history, or self-report if medical records do not accompany subject or are unable to be collected;
- •Patients unable to sign an informed patient consent;
- •Anticipated amputation of involved limb;
- •Neurological conditions (i.e. spinal cord injury or traumatic brain injury) that may prevent full participation in CS rehabilitation or potentially confound study outcome measures (i.e. balance and gait) per physician discretion
- •Current systemic infection;
- •Local infection of the involved muscle group;
Arms & Interventions
Autologous BM-MNCs High Dose
Administration of autologous bone marrow mononuclear cells at High dose (700,000 cells/cc of tissue)
Intervention: Intramuscular administration of autologous BM-MNCs
Autologous BM-MNCs Low Dose
Administration of autologous bone marrow mononuclear cells at a Low dose (350,000 cells/cc of tissue)
Intervention: Intramuscular administration of autologous BM-MNCs
Outcomes
Primary Outcomes
Efficacy as determined by muscle strength
Time Frame: 6 weeks, 3 months, 6 months, and 12 months
Change in muscle strength compared to baseline and contralateral leg as measured by manual muscle testing and Biodex.
Safety as determined by incidence of combined adverse events related to study agent intervention
Time Frame: Enrollment through 24 months
Local and systemic reactions, serious adverse events and unexpected serious adverse events.
Secondary Outcomes
- Questionnaire - Physical Activity(Baseline through 24 months)
- Lower extremity sensation(Baseline through 12 months)
- Ankle range of motion(Baseline through 12 months)
- Safety as determined by evidence of tumor formation(Baseline through 12 months)
- Efficacy as determined by muscle regeneration(Baseline through 12 months)
- Nerve conduction(Baseline and 6 months)
- Gait analysis(Week 6 through 12 months)
- Gait speed(Week 6 through 12 months)
- Questionnaire - Pain(Baseline through 24 months)
- Wound healing(Baseline through 12 months)
- Gait endurance(Week 6 through 12 months)
- Questionnaire - Function(Baseline through 24 months)
- Balance(Week 6 through 12 months)