Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

BM-MNCs for Lower Extremity Compartment Syndrome Injury

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03880656
Recruitment Status : Not yet recruiting
First Posted : March 19, 2019
Last Update Posted : June 17, 2019
Sponsor:
Collaborator:
University of Pittsburgh
Information provided by (Responsible Party):
Kenton W. Gregory, Oregon Health and Science University

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.

Condition or disease Intervention/treatment Phase
Compartment Syndrome Traumatic Lower Extremity Biological: Intramuscular administration of autologous BM-MNCs Phase 1

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a two-stage, randomized, unblinded, multicenter (two sites), controlled phase 1 clinical trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Autologous Bone Marrow Mononuclear Cell Administration for Lower Extremity Compartment Syndrome Injury
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


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)
Biological: Intramuscular administration of autologous BM-MNCs
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)
Biological: Intramuscular administration of autologous BM-MNCs
Intramuscular administration of autologous BM-MNCs at either a low or high cell dose.




Primary Outcome Measures :
  1. 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.

  2. 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/or Biodex.


Secondary Outcome Measures :
  1. Safety as determined by evidence of tumor formation [ Time Frame: Baseline through 12 months ]
    Magnetic resonance imaging (MRI) and/or computed tomography (CT)

  2. 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

  3. Nerve conduction [ Time Frame: Baseline and 6 months ]
    Nerve conduction velocity test

  4. Wound healing [ Time Frame: Baseline through 12 months ]
    Number of days until wound closure at the site of fasciotomy of the anterior compartment.

  5. Lower extremity sensation [ Time Frame: Baseline through 12 months ]
    Sensation as measured by Semmes Weinstein Monofilament.

  6. 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.

  7. 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.

  8. Gait endurance [ Time Frame: Week 6 through 12 months ]
    Gait endurance measured using the 6-Minute Walk Test.

  9. Gait speed [ Time Frame: Week 6 through 12 months ]
    Gait speed measured using the 10 Meter Walk Test.

  10. Balance [ Time Frame: Week 6 through 12 months ]
    Balance assessed by single limb stance time.

  11. 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.

  12. 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).

  13. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Healthy contralateral lower extremity for comparison testing
  • 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
  • Have sufficient skin to allow for tissue approximation for wound closure
  • Anterior compartment muscle volume between 200 - 280 cc as determined by MRI/CT
  • Within the institutions' clinical reference ranges for screening laboratory panels: CBC with differential, Prothrombin time/PTT/INR, liver function tests, HbA1C, and serum creatinine;
  • Negative HIV test
  • 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 as indicated by past medical history, self-report, or elevated HbA1C consistent with diabetes;
  • 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 or contralateral limb precludes comparison studies; significant injury to contralateral limb that would preclude comparative testing;
  • Spinal cord injury
  • Moderate to severe traumatic brain injury defined as a loss of consciousness for more than 30 minutes and/or an abnormal brain MRI/CT scan;
  • 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) ;
  • Insufficient skin for tissue approximation for wound closure or lower extremity burns that may affect wound closure;
  • Significant tissue loss in involved muscle(s) (i.e., extensive debridement such that there is insufficient residual tissue for stem cell administration and subsequent engraftment);
  • Lower extremity compound fracture;
  • Anterior tibialis muscle volume less than 200 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.

Information from the National Library of Medicine

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): NCT03880656


Contacts
Layout table for location contacts
Contact: Kenton W Gregory, MD 503-418-0091 gregoryk@ohsu.edu
Contact: Lisa A Buckley, MPH 503-418-0085 buckleyl@ohsu.edu

Locations
Layout table for location information
United States, Oregon
Oregon Health & Science University Not yet recruiting
Portland, Oregon, United States, 97239
Contact: Kenton W Gregory, MD    503-418-0091    gregoryk@ohsu.edu   
United States, Pennsylvania
University of Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: J. Peter Rubin, MD    412-383-8080    rubinpj@UPMC.edu   
Sponsors and Collaborators
Oregon Health and Science University
University of Pittsburgh
Investigators
Layout table for investigator information
Principal Investigator: Kenton W Gregory, MD Oregon Health and Science University

Layout table for additonal information
Responsible Party: Kenton W. Gregory, Director, Oregon Center for Regenerative Medicine, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT03880656     History of Changes
Other Study ID Numbers: STUDY00018011
First Posted: March 19, 2019    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kenton W. Gregory, Oregon Health and Science University:
mononuclear cells
Additional relevant MeSH terms:
Layout table for MeSH terms
Compartment Syndromes
Syndrome
Disease
Pathologic Processes
Muscular Diseases
Musculoskeletal Diseases
Vascular Diseases
Cardiovascular Diseases