BM-MNCs for Lower Extremity Compartment Syndrome Injury

NCT ID: NCT03880656

Last Updated: 2025-04-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-04
• Study Completion Date: 2026-06-30

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.

Conditions

Compartment Syndrome Traumatic Lower Extremity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Autologous BM-MNCs High Dose

Administration of autologous bone marrow mononuclear cells at High dose (700,000 cells/cc of tissue)

Group Type: EXPERIMENTAL

Intramuscular administration of autologous BM-MNCs

Intervention Type: BIOLOGICAL

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

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Autologous BM-MNCs Low Dose

Administration of autologous bone marrow mononuclear cells at a Low dose (350,000 cells/cc of tissue)

Group Type: EXPERIMENTAL

Intramuscular administration of autologous BM-MNCs

Intervention Type: BIOLOGICAL

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

Interventions

Intramuscular administration of autologous BM-MNCs

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

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oregon Health and Science University

OTHER

Sponsor Role: lead

Responsible Party

Kenton W. Gregory

Director, Oregon Center for Regenerative Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kenton W Gregory, MD

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

Locations

Oregon Health & Science University

Portland, Oregon, United States

Countries

United States

Other Identifiers

STUDY00018011

Identifier Type: -

Identifier Source: org_study_id