Defining the Pathophysiology of Heterotopic Ossification: A Prospective Study

NCT04867018 | Withdrawn

• 1 other identifier: 333333
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Our overarching aim is to define the pathophysiology, epidemiology, and natural history of HO by following patients from date of injury until full wound healing has occurred and the window for HO has passed. Specific aims Aim 1: To classify the acute and chronic physiologic profiles of fracture patients and how they relate to the development of HO. Here the investigators will look at the systemic derangements to patients' coagulation, fibrinolytic, and inflammatory profiles. Aim 2: Identify the true incidence and time course of HO development after traumatic fracture. To accomplish this the investigators will look at patients who have sustained hip fracture, midshaft/distal femur fracture, humerus fracture, proximal radius fracture, and elbow dislocation/fractures and track follow-up images up to one year after injury looking for HO. Aim 3: Define the histologic characteristics of HO development. To accomplish this aim the investigators will perform a histologic analysis on a sample of injured muscle surrounding the fracture area. Aim 4: To determine what comorbid, iatrogenic, or environmental influences are associated with the formation of HO. To achieve this aim the investigators will evaluate data including injury type, surgery type, operative duration, surgical approach, contamination (open vs closed injury), complications (malunion, nonunion, infection, hardware failure, removal of hardware), hardware type, comorbidities (smoking, cardiac history, diabetes), and medications.

Conditions

Heterotopic Ossification

Outcome Measures

Primary Outcomes (6)

• Change of coagulation from baseline during hospitalization as measured by platelet count

  The normal platelet count range is 150,000-450,000/uL. Typically a decrease in platelet count is associated with activation of coagulation, and increases represent a rebound reparative period. This is not always the case, so we will record both increases and decreases in platelet count, specifically.

  Change of platelet count from baseline and during hospitalization (approximately 1-28 days)

• Change of coagulation from baseline during hospitalization as measured by thrombin-antithrombin (TAT) complexes

  The normal range for thrombin-antithrombin (TAT) complexes is 1-4 ug/L. An increase in thrombin-antithrombin (TAT) complexes will indicate activation of coagulation.

  Change of thrombin-antithrombin (TAT) from baseline and during hospitalization (approximately 1-28 days)

• Change of fibrinolysis from baseline during hospitalization as measured by plasmin-antiplasmin complex (PAP)

  The normal range for Plasmin-antiplasmin complex (PAP) is 120-700ug/L. An increase in plasmin-antiplasmin complex (PAP) will indicate activation of fibrinolysis.

  Change of plasmin-antiplasmin complex (PAP) from baseline and during hospitalization (approximately 1-28 days)

• Change of fibrinolysis from baseline during hospitalization as measured by D-dimer

  The normal range for D-dimer is \<0.5mg/L. An increase in D-dimer will indicate activation of fibrinolysis.

  Change of D-dimer from baseline and during hospitalization (approximately 1-28 days)

• Change of inflammation from baseline during hospitalization as measured by C-reactive protein (CRP)

  The normal range for C-reactive protein (CRP) is \<10mg/L. An increase in C-reactive protein (CRP) will indicate activation of inflammation.

  Change of C-reactive protein (CRP) from baseline and during hospitalization (approximately 1-28 days)

• Change of inflammation from baseline during hospitalization as measured by IL-6

  The normal range for IL-6 is 0-5pg/mL or \<15pg/mL. An increase in IL-6 will indicate activation of inflammation.

  Change of IL-6 from baseline and during hospitalization (approximately 1-28 days)

Study Arms (2)

Orthopaedic Trauma, Pediatrics and Joint Patients

Patients will have an additional 9ml of blood drawn during their normal course of care for this study up to 4 times. Intraoperatively, we will request a tissue sample of the debrided injured muscle from the area where the surgeon is operating. There will be no additional tissue sample taken during the surgery, but what is removed in the normal course of the operation will be used for analysis in our study.

Healthy Volunteer

Blood will be taken from healthy, nonpregnant adults who weigh at least 110 pounds. All volunteers will have a single blood draw of 100ml at the time of consent.

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Injured patients will be recruited from the orthopedic trauma, pediatrics and joints service from clinics. Healthy volunteers will be solicited from flyers around the VUMC medical center and through ResearchMatch.

You may qualify if:

• Any patient treated in our hospital system from initial IRB approval until we reach our enrollment quota that are diagnosed with HO, hip fracture, midshaft/distal femur fracture, humerus fracture, proximal radius fracture, and elbow dislocation/fracture. This includes patients in all age groups and of all genders.
• Patients with a diagnosis of HO, hip fracture, midshaft/distal femur fracture, humerus fracture, proximal radius fracture, or elbow fracture must be receiving operative treatment for their injury.
• Patients with concurrent trauma will be grouped into a sub-analysis.

You may not qualify if:

• Patients with pathologic fractures.
• Non-operative patients other than elbow dislocation patients
• Pregnant Women
• Patients who do not intend to follow-up at Vanderbilt
• Arm 2- Healthy Volunteers
• Volunteers (male or female) between ages of 18-70
• Weight greater than 110lbs
• Chronic medical conditions such as diabetes, hypertension, high cholesterol, rheumatologic disorders, infections, etc.
• History of recent trauma or burn injury
• Recent inpatient admission within the last year
• Pregnant females or people on hormone replacement therapy
• People on any anticoagulant medication or NSAIDS

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt Children's Orthopaedics

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Ossification, Heterotopic

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Of Orthopaedics, Pathology, Pharmacology, and Pediatrics

Study Record Dates

• First Submitted: March 19, 2021
• First Posted: April 30, 2021
• Study Start: June 1, 2022
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: March 9, 2022

Record last verified: 2022-02

Locations

US (1)