Gene Expression in Lower Extremity Acute Traumatic Compartment Syndrome

Genetics and Local Gene Expression in Lower Extremity Acute Traumatic Compartment Syndrome

The purpose of this study is to evaluate both genotypic differences and differences in local gene expression in individuals who develop acute traumatic compartment syndrome relative to control patients with at-risk lower extremity fractures who do not develop compartment syndrome.

Study Overview

• Status: Enrolling by invitation
• Conditions: Tibial Shaft Fracture; Tibial Plateau Fracture
• Intervention / Treatment: Procedure: Acute injury without compartment syndrome; Procedure: Acute injury with compartment syndrome; Procedure: Exertional compartment syndrome

Detailed Description

Acute compartment syndrome is associated with infection, contractures, fracture non-union, and chronic pain syndromes. The most common cause of acute compartment syndrome is fracture. Individuals with compartment syndrome associated with a lower extremity fracture have demonstrated worse patient reported outcome scores compared to individuals who suffer lower extremity fractures alone.

The pathophysiology of compartment syndrome has been traditionally described as loss of tissue perfusion and subsequent cellular anoxia related to supra-physiologic pressure within a closed myofascial space. Both animal and clinical studies have suggested that compartment syndrome develops when the intra-compartmental pressure approaches systemic diastolic blood pressure. However, other studies have demonstrated that high absolute compartment pressures and/or narrowed delta pressures have poor sensitivity for predicting compartment syndrome, suggesting that the pathophysiology of compartment syndrome is likely more complex than the currently accepted understanding of the disease process.

Animal models suggest that fracture promotes inflammation and exacerbates microvascular dysfunction, which may act synergistically with elevated intra-compartmental pressures to create clinical compartment syndrome. It is known that fracture causes microvascular damage and inflammation in surrounding muscle tissue. Several models have demonstrated that the microvascular environment in compartment syndrome is characterized by tenuous, intermittent blood supply to the musculature, which displays asymmetric microvascular dysfunction in response to elevated compartment pressures. Similarly, recent animal research has demonstrated that elevated intra-compartmental pressure is associated with a pro-inflammatory state, which directly contributes to skeletal muscle injury and may exacerbate microvascular injury.

It is unknown whether individual genomic and/or transcriptomic variability is clinically relevant with respect to response to fracture or the development of compartment syndrome. However, there is evidence from the vascular surgery literature in both animal and human models that individual variability in gene expression meaningfully affects skeletal muscle response to acute ischemia. The investigators hypothesize that there may be an individual pre-disposition to developing clinical compartment syndrome in the setting of at-risk fractures which manifests itself in the cellular response to inflammation and low grade ischemia. The overarching goal of this study is to characterize cellular level dysfunction in human compartment syndrome and to determine whether there are unique gene expression profiles associated with the development of clinical compartment syndrome. Specific aim 1 of this study is to compare genetic and transcriptomic differences individuals with high-risk tibia fractures who do not develop compartment syndrome and individuals with high-risk tibia fractures who do develop clinical compartment syndrome. Specific aim 2 of this study is to to compare genetic differences between acute compartment syndrome patients and chronic exertional compartment syndrome patients.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Orthopaedic Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient 18+ years of age. English speaking.
• Patients with the clinical diagnosis of lower leg acute compartment syndrome secondary to tibial shaft or tibial plateau fracture.
• Patients without clinical compartment syndrome undergoing operative intervention within 48 hours of injury for tibial shaft or tibial plateau fractures.
• Patients with the clinical diagnosis of exertional compartment syndrome with planned surgical intervention.

Exclusion Criteria:

• Non-english speaking participants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Acute tibial shaft or tibial plateau fractures without compartment syndrome; Patients with acute lower leg fractures who do not have clinical compartment syndrome.	Procedure: Acute injury without compartment syndrome; Acute tibial shaft or tibial plateau fractures who do not have clinical compartment syndrome. Muscle punch biopsy of the anterior compartment will be taken.
Other: Acute tibial shaft or tibial plateau fractures with compartment syndrome.; Patients with acute lower leg fractures with acute compartment syndrome.	Procedure: Acute injury with compartment syndrome; Acute tibial shaft or tibial plateau fractures who have clinical compartment syndrome. Muscle punch biopsy of the anterior compartment will be taken.
Other: Exertional compartment syndrome; Patients with a diagnosis of exertional compartment syndrome who are planning to undergo surgical procedure to release the compartment fascia will be recruited to participate prior to surgical intervention.	Procedure: Exertional compartment syndrome; For patients with exertional compartment syndrome, a muscle biopsy will be obtained from affected extremity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myostatin (% increase)	The investigators primary marker of interest is myostatin. The investigators will determine the (%) increase in myostatin levels in muscle tissues between compartment syndrome patients versus fracture controls. (%) increase in myostatin levels in muscle tissues between compartment syndrome patients versus patients with exertional compartment syndrome will also be determined. The measurement tool is polymerase chain reaction (PCR).	Immediately after the muscle tissue harvest procedure.

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Justin Haller, M.D., University of Utah Orthopaedics

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2022
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: August 15, 2022
• First Submitted That Met QC Criteria: August 25, 2022
• First Posted (Actual): August 30, 2022

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: gene expression; acute compartment syndrome; tibial shaft or tibial plateau fracture; without acute compartment syndrome; exertional compartment syndrome; myostatin
• Additional Relevant MeSH Terms: Knee Fractures; Wounds and Injuries; Leg Injuries; Fractures, Bone; Knee Injuries; Tibial Fractures; Tibial Plateau Fractures
• Other Study ID Numbers: 152310

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No