Heterotopic OssificationNCT04867018
Defining the Pathophysiology of Heterotopic Ossification: A Prospective Study
An observational study of Heterotopic Ossification, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 70 years
- Conditions the study is for
- Heterotopic Ossification
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2022to 1 Jun 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 70 years
- All sexes
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
- Volunteers (male or female) between ages of 18-70
- Weight greater than 110lbs
Who cannot join
- 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
- Chronic medical conditions such as diabetes, hypertension, high cholesterol, rheumatologic disorders, infections, etc.
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt Children's Orthopaedics
Nashville, Tennessee, 37232
About this study
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
Read more
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.
Read the detailed description
The aforementioned general inclusion/exclusion criteria will be used to determine patient eligibility. All eligible patients will be identified using a patient list from StarPanel provided by the managing team. The study will proceed until all eligible patients are enrolled (our goal for this study is to recruit at least 1000 patients). If the patient agrees to participate in the study they will be asked to sign an informed consent document by the research team.
Arm 1
On Admission:
Demographics and Comorbidities The following patient data will be recorded: age, gender, height, weight, date of admission, date of discharge, diagnosis, injury time, injury type, laterality, surgical approach, implants used, duration of surgery, time to union, contamination (open vs closed injury), comorbidities (smoking, cardiac history, diabetes, etc.), current medications.
Labs Patients will have an additional 9ml of blood drawn during their normal course of care for this study up to 4 times. The draws will happen while they are an inpatient in the hospital. The timing of the draw will surround the timing of their operation. They will have blood drawn within 24 hours before surgery, immediately after surgery, 24 hours after surgery, and 72 hours after surgery. Labs values, including CBC with dif, CMP, D-Dimer, CRP, PT/INR, PTT, fibrinogen, lactate, PAI-1, plasminogen activation assay, chromogenics, plasmin-anti-plasmin complex, and phosphate will be collected for this study. Patient often have a blood draw before and after surgery, one for typing and another as part of routine labs. The investigators will use the remnants of those blood draws which will be stored in the Vanderbilt Lab core and retrieved for further analysis by key research personnel. The remaining plasma will come from another remnant blood or an extra draw.
Tissue Samples Intraoperatively, investigators 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. The amount of tissue that will be analyzed for this study will vary based on how much of the injured muscle the operating physician decides to take in their normal course of operation. If the tissue sample is not readily accessible, such as in the case of an intramedullary nail fixation, the investigators will forgo the sample.
Follow-up
Radiographic imaging and notes from follow-up appointments will be examined for complications, such as: malunion, nonunion, infection, hardware failure, removal of hardware, presence of amorphous tissue calcification, symptomatic HO, or asymptomatic HO. Time to the development of calcific complications, will also be recorded. To document post-surgical complications the investigators will use imaging, photographs, progress notes, clinic notes, ICD-9 codes, CPT codes and operative reports.
The time frame for follow up visits will be based on the preference of the participant's physician. Any complications resulting from the injury will be documented. Complications will be documented if they occur within 2 years of injury. No study activities will take place during this time frame other than recording complications.
Clinical Practice Guidelines
All patients will be treated according to established clinical practice guidelines at Vanderbilt Children's Hospital or Vanderbilt Medical Center, decreasing the chance that differences in the patients' results and outcomes result from variability of the treating physician.
Arm 2 Volunteers Blood Draw 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. No more than 2.5% of the volunteer's blood volume will be taken at any point (100ml maximum for a 110lb person in one sitting).
- Conditions
- Heterotopic Ossification
- Medical subject headings
- Ossification, Heterotopic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Change of IL-6 from baseline and during hospitalization (approximately 1-28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2021
- Study start1 Jun 2022 (estimated)
- Primary completion1 Jun 2024 (estimated)
- Study completion1 Jun 2024 (estimated)
Why it stopped: study was never fully reopened with the intuitional review board
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heterotopic OssificationStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jon Schoenecker, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04867018
- Sponsor's protocol ID
- 333333
- Status last verified
- Feb 2022
- First submitted
- 19 Mar 2021
- Last updated
- 9 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining the Pathophysiology of Heterotopic Ossification: A Prospective Study
- ClinicalTrials.gov ID
- NCT04867018
- Acronym / sponsor ID
- 333333
- Conditions
- Heterotopic Ossification
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: study was never fully reopened with the intuitional review board
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 1 Jun 2022 (estimated)
- Primary completion
- 1 Jun 2024 (estimated)
- Study completion
- 1 Jun 2024 (estimated)
- First posted
- 30 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The aforementioned general inclusion/exclusion criteria will be used to determine patient eligibility. All eligible patients will be identified using a patient list from StarPanel provided by the managing team. The study will proceed until all eligible patients are enrolled (our goal for this study is to recruit at least 1000 patients). If the patient agrees to participate in the study they will be asked to sign an informed consent document by the research team.
Arm 1
On Admission:
Demographics and Comorbidities The following patient data will be recorded: age, gender, height, weight, date of admission, date of discharge, diagnosis, injury time, injury type, laterality, surgical approach, implants used, duration of surgery, time to union, contamination (open vs closed injury), comorbidities (smoking, cardiac history, diabetes, etc.), current medications.
Labs Patients will have an additional 9ml of blood drawn during their normal course of care for this study up to 4 times. The draws will happen while they are an inpatient in the hospital. The timing of the draw will surround the timing of their operation. They will have blood drawn within 24 hours before surgery, immediately after surgery, 24 hours after surgery, and 72 hours after surgery. Labs values, including CBC with dif, CMP, D-Dimer, CRP, PT/INR, PTT, fibrinogen, lactate, PAI-1, plasminogen activation assay, chromogenics, plasmin-anti-plasmin complex, and phosphate will be collected for this study. Patient often have a blood draw before and after surgery, one for typing and another as part of routine labs. The investigators will use the remnants of those blood draws which will be stored in the Vanderbilt Lab core and retrieved for further analysis by key research personnel. The remaining plasma will come from another remnant blood or an extra draw.
Tissue Samples Intraoperatively, investigators 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. The amount of tissue that will be analyzed for this study will vary based on how much of the injured muscle the operating physician decides to take in their normal course of operation. If the tissue sample is not readily accessible, such as in the case of an intramedullary nail fixation, the investigators will forgo the sample.
Follow-up
Radiographic imaging and notes from follow-up appointments will be examined for complications, such as: malunion, nonunion, infection, hardware failure, removal of hardware, presence of amorphous tissue calcification, symptomatic HO, or asymptomatic HO. Time to the development of calcific complications, will also be recorded. To document post-surgical complications the investigators will use imaging, photographs, progress notes, clinic notes, ICD-9 codes, CPT codes and operative reports.
The time frame for follow up visits will be based on the preference of the participant's physician. Any complications resulting from the injury will be documented. Complications will be documented if they occur within 2 years of injury. No study activities will take place during this time frame other than recording complications.
Clinical Practice Guidelines
All patients will be treated according to established clinical practice guidelines at Vanderbilt Children's Hospital or Vanderbilt Medical Center, decreasing the chance that differences in the patients' results and outcomes result from variability of the treating physician.
Arm 2 Volunteers Blood Draw 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. No more than 2.5% of the volunteer's blood volume will be taken at any point (100ml maximum for a 110lb person in one sitting).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- Up to 70 years
- Sex
- All
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
- Volunteers (male or female) between ages of 18-70
- Weight greater than 110lbs
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change of coagulation from baseline during hospitalization as measured by platelet count
Time frame: Change of platelet count from baseline and during hospitalization (approximately 1-28 days)
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 coagulation from baseline during hospitalization as measured by thrombin-antithrombin (TAT) complexes
Time frame: Change of thrombin-antithrombin (TAT) from baseline and during hospitalization (approximately 1-28 days)
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 fibrinolysis from baseline during hospitalization as measured by plasmin-antiplasmin complex (PAP)
Time frame: Change of plasmin-antiplasmin complex (PAP) from baseline and during hospitalization (approximately 1-28 days)
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 fibrinolysis from baseline during hospitalization as measured by D-dimer
Time frame: Change of D-dimer from baseline and during hospitalization (approximately 1-28 days)
The normal range for D-dimer is <0.5mg/L. An increase in D-dimer will indicate activation of fibrinolysis.
Change of inflammation from baseline during hospitalization as measured by C-reactive protein (CRP)
Time frame: Change of C-reactive protein (CRP) from baseline and during hospitalization (approximately 1-28 days)
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 inflammation from baseline during hospitalization as measured by IL-6
Time frame: Change of IL-6 from baseline and during hospitalization (approximately 1-28 days)
The normal range for IL-6 is 0-5pg/mL or <15pg/mL. An increase in IL-6 will indicate activation of inflammation.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heterotopic Ossification, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 9 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of coagulation from baseline during hospitalization as measured by platelet count (time frame: Change of platelet count from baseline and during hospitalization (approximately 1-28 days)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2022.