BM-MNCs for Lower Extremity Compartment Syndrome Injury

February 5, 2024 updated by: Kenton W. Gregory, Oregon Health and Science University

Autologous Bone Marrow Mononuclear Cell Administration for Lower Extremity Compartment Syndrome Injury

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Estimated)

18

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 Contact

Study Locations

    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University

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 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Autologous BM-MNCs High Dose
Administration of autologous bone marrow mononuclear cells at High dose (700,000 cells/cc of tissue)
Intramuscular administration of autologous BM-MNCs at either a low or high cell dose.
No Intervention: Observational Control
Standard of care provided for subjects that have undergone a fasciotomy following a diagnosis of compartment syndrome. No autologous bone marrow mononuclear cells will be administered.
Experimental: Autologous BM-MNCs Low Dose
Administration of autologous bone marrow mononuclear cells at a Low dose (350,000 cells/cc of tissue)
Intramuscular administration of autologous BM-MNCs at either a low or high cell dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Enrollment through 24 months
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.
6 weeks, 3 months, 6 months, and 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety as determined by evidence of tumor formation
Time Frame: Baseline through 12 months
Magnetic resonance imaging (MRI) and/or computed tomography (CT)
Baseline through 12 months
Efficacy as determined by muscle regeneration
Time Frame: Baseline through 12 months
Magnetic resonance imaging (MRI) and/or computed tomography (CT) to measure muscle volume
Baseline through 12 months
Nerve conduction
Time Frame: Baseline and 6 months
Nerve conduction velocity test
Baseline and 6 months
Wound healing
Time Frame: Baseline through 12 months
Number of days until wound closure at the site of fasciotomy of the anterior compartment.
Baseline through 12 months
Lower extremity sensation
Time Frame: Baseline through 12 months
Sensation as measured by Semmes Weinstein Monofilament.
Baseline through 12 months
Ankle range of motion
Time Frame: Baseline through 12 months
Range of Motion (ROM): active and passive dorsi/plantar flexion ROM assessed using a goniometer.
Baseline through 12 months
Gait analysis
Time Frame: Week 6 through 12 months
Change in gait kinematics: gait will be recorded using a Tekscan Pressure Mapping system where each sequential footstep is recorded along with synchronized video.
Week 6 through 12 months
Gait endurance
Time Frame: Week 6 through 12 months
Gait endurance measured using the 6-Minute Walk Test.
Week 6 through 12 months
Gait speed
Time Frame: Week 6 through 12 months
Gait speed measured using the 10 Meter Walk Test.
Week 6 through 12 months
Balance
Time Frame: Week 6 through 12 months
Balance assessed by single limb stance time.
Week 6 through 12 months
Questionnaire - Pain
Time Frame: Baseline through 24 months
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.
Baseline through 24 months
Questionnaire - Function
Time Frame: Baseline through 24 months
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).
Baseline through 24 months
Questionnaire - Physical Activity
Time Frame: Baseline through 24 months
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).
Baseline through 24 months

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Kenton W Gregory, MD, Oregon Health and Science University

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 (Actual)

December 4, 2019

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

March 13, 2019

First Submitted That Met QC Criteria

March 15, 2019

First Posted (Actual)

March 19, 2019

Study Record Updates

Last Update Posted (Estimated)

February 7, 2024

Last Update Submitted That Met QC Criteria

February 5, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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