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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Intramuscular administration of autologous BM-MNCs at either a low or high cell dose.
Oregon Health & Science University
Portland, Oregon, United States
Safety as determined by incidence of combined adverse events related to study agent intervention
Local and systemic reactions, serious adverse events and unexpected serious adverse events.
Time frame: Enrollment through 24 months
Efficacy as determined by muscle strength
Change in muscle strength compared to baseline and contralateral leg as measured by manual muscle testing and Biodex.
Time frame: 6 weeks, 3 months, 6 months, and 12 months
Safety as determined by evidence of tumor formation
Magnetic resonance imaging (MRI) and/or computed tomography (CT)
Time frame: Baseline through 12 months
Efficacy as determined by muscle regeneration
Magnetic resonance imaging (MRI) and/or computed tomography (CT) to measure muscle volume
Time frame: Baseline through 12 months
Nerve conduction
Nerve conduction velocity test
Time frame: Baseline and 6 months
Wound healing
Number of days until wound closure at the site of fasciotomy of the anterior compartment.
Time frame: Baseline through 12 months
Lower extremity sensation
Sensation as measured by Semmes Weinstein Monofilament.
Time frame: Baseline through 12 months
Ankle range of motion
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Range of Motion (ROM): active and passive dorsi/plantar flexion ROM assessed using a goniometer.
Time frame: Baseline through 12 months
Gait analysis
Change in gait kinematics: gait will be recorded using a Tekscan Pressure Mapping system where each sequential footstep is recorded along with synchronized video.
Time frame: Week 6 through 12 months
Gait endurance
Gait endurance measured using the 6-Minute Walk Test.
Time frame: Week 6 through 12 months
Gait speed
Gait speed measured using the 10 Meter Walk Test.
Time frame: Week 6 through 12 months
Balance
Balance assessed by single limb stance time.
Time frame: Week 6 through 12 months
Questionnaire - Pain
Pain measured using the Numeric Pain Rating Scale (NPRS). The participant is asked to make three pain ratings (0 to 10; 0 - no pain, 10 - worst pain), corresponding to current, best and worst pain experienced over the past 24 hours. The average of the 3 ratings is used to represent the patient's level of pain over the previous 24 hours.
Time frame: Baseline through 24 months
Questionnaire - Function
Lower extremity function assessed using the Lower Extremity Functional Scale (LEFS). Total score (0 to 80; higher score = better outcome) is reported as a sum of 20 responses regarding functional activities (0 - extreme difficulty or unable to perform, 4 - no difficulty).
Time frame: Baseline through 24 months
Questionnaire - Physical Activity
Physical activity measured by the international physical activity questionnaire (IPAQ). Scores are reported as categorical (low, moderate, high) and/or continuous (metabolic equivalent minutes per week).
Time frame: Baseline through 24 months