Clinical trial NCT03880656: BM-MNCs for Lower Extremity Compartment Syndrome Injury
Official title: Autologous Bone Marrow Mononuclear Cell Administration for Lower Extremity Compartment Syndrome Injury
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Compartment Syndrome Traumatic Lower Extremity
Keywords: mononuclear cells
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2019-03-19
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a two-stage, randomized, unblinded, multicenter (two sites), controlled phase 1 clinical trial.
Primary purpose: TREATMENT

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.

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)
* Female subjects must be of non-childbearing potential or must be using adequate contraception
* If female subject is of childbearing potential, subject must have a negative pregnancy test at screening
* Willing and able to adhere to the study schedule

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;
* Use of ventilator that would preclude rehabilitation protocols;
* Lack of access or unwillingness to complete standard of care course of physical therapy rehabilitation;
* Life expectancy 12 months or less;
* Bone marrow disorders (i.e. leukemia, aplastic anemia, lymphoma) ;
* Inability to close the fasciotomy wound or lower extremity burns that may affect wound closure
* Extensive tissue loss due to debridement resulting in insufficient residual tissue for stem cell administration and subsequent engraftment
* Lower extremity compound fracture type II or III (Gustilo-Anderson classification);
* Anterior tibialis muscle volume less than 100 cc or greater than 280 cc as determined by MRI/CT;
* Evidence of any past or present clinically significant medical condition that would impair wound healing
* History or clinical manifestations of significant renal, hepatic, cardiovascular, metabolic, neurologic, psychiatric, or other condition that would preclude participation in the study as determined by the investigator or the investigator's designee;
* Any reason, considered by the principal investigator or designee, to preclude subject enrollment in the study that might represent a threat to the subject's health or safety.

Primary outcomes:
measure: Safety as determined by incidence of combined adverse events related to study agent intervention
timeFrame: Enrollment through 24 months
measure: Efficacy as determined by muscle strength
timeFrame: 6 weeks, 3 months, 6 months, and 12 months
Secondary outcomes:
measure: Safety as determined by evidence of tumor formation
timeFrame: Baseline through 12 months
measure: Efficacy as determined by muscle regeneration
timeFrame: Baseline through 12 months
measure: Nerve conduction
timeFrame: Baseline and 6 months
measure: Wound healing
timeFrame: Baseline through 12 months
measure: Lower extremity sensation
timeFrame: Baseline through 12 months
measure: Ankle range of motion
timeFrame: Baseline through 12 months
measure: Gait analysis
timeFrame: Week 6 through 12 months
measure: Gait endurance
timeFrame: Week 6 through 12 months
measure: Gait speed
timeFrame: Week 6 through 12 months
measure: Balance
timeFrame: Week 6 through 12 months
measure: Questionnaire - Pain
timeFrame: Baseline through 24 months
measure: Questionnaire - Function
timeFrame: Baseline through 24 months
measure: Questionnaire - Physical Activity
timeFrame: Baseline through 24 months
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Kenton W Gregory, MD
role: PRINCIPAL_INVESTIGATOR
References: