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Phase I portion was completed. Phase II will now be completed at a different institution.
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| Name | Class |
|---|---|
| United States Department of Defense | FED |
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This is a small-scale proof-of concept clinical trial of amobarbital as a treatment to prevent post-traumatic osteoarthritis in fractured ankle joints. The study is a double blind, prospective, randomized, placebo-controlled, stepwise trial. Amobarbital will be delivered to ankle joints in solution with hyaluronic acid (HA) as a vehicle. Amobarbital/HA injections (active dose) will be compared to HA alone (placebo dose). Our primary goal is to confirm safety, but we will also assess whether treatment improves chondrocyte viability and decreases synovial inflammation. The intervention that will be utilized has proven to be effective using vitro and in vivo models. The study team will assess safety and begin to evaluate efficacy of amobarbital/Gel-One in patients having sustained tibial pilon fractures. The study team will use advanced imaging-based methods we have developed to characterize how joints subjected to varying levels of fracture severity and residual elevated contact stress respond in treated and control groups.
This is a small-scale proof-of concept clinical trial of amobarbital as a treatment to prevent post-traumatic osteoarthritis in fractured ankle joints. The study is a double blind, prospective, randomized, placebo-controlled, stepwise trial. Amobarbital will be delivered to ankle joints in solution with hyaluronic acid (HA) as a vehicle. Amobarbital/HA injections (active dose) will be compared to HA alone (placebo dose). Our primary goal is to confirm safety, but we will also assess whether treatment improves chondrocyte viability and decreases synovial inflammation. The intervention that will be utilized has proven to be effective using vitro and in vivo models. The study team will assess safety and begin to evaluate efficacy of amobarbital/Gel-One in patients having sustained tibial pilon fractures. The study team will use advanced imaging-based methods we have developed to characterize how joints subjected to varying levels of fracture severity and residual elevated contact stress respond in treated and control groups.
Phase I:6 subjects will be treated with a single dose open label, and safety measures will be assessed.
Phase II: Once initial safety is confirmed, 20 amobarbital:10 control subjects will be treated with the single dose at the initial operation.
Assuming continued safety, an additional 20 amobarbital:10 control subjects will be treated with two doses and evaluated. The second dose of 2.5 mM amobarbital will be administered during the second operation.
Subjects will participate in the following procedures:
SOC surgical intervention Randomization to Amobarbital/Gel-One arm or control arm X-rays CT scans Blood and urine Questionnaires
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase I single amobarbital/Gel-One dose | Experimental | Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II. |
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| Phase IIa Part 1 amobarbital/Gel-One dose | Active Comparator | 20 subjects will be randomized to amobarbital/Gel-One single dose. |
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| Phase IIa Part 1 Placebo | Placebo Comparator | 10 subjects will be randomized to amobarbital/Gel-One single dose. |
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| Phase IIa Part 2 amobarbital/Gel-One dose | Active Comparator | 20 subjects will be randomized to one dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention. |
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| Phase IIa Part 2 placebo | Placebo Comparator | 20 subjects will be randomized to one dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| amobarbital/Gel-One (one dose) | Drug | One dose of amobarbital/Gel-One during the initial surgical intervention |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Systemic Adverse Events Defined as Abnormal Laboratory Values and Number Where Amobarbital is Detected Systemically | Safety Measures: CBC and standard clinical chemistry assays to quantify circulating, ALT, AST, Bilirubin, Creatinine, and BUN and the measurement of urine protein content will be evaluated and the number of participants with clinically significant abnormal laboratory values will be determined. Presence of amobarbital will be tested in blood and urine samples and the number of subjects it is detected in will be reported. | Pre-op baseline on the day before external fixation surgery (within 24 hours of injury), immediately post-op, and at 1, 2, and 4 days post-op. At the time of internal fixation (3-21 days after external fixation) and at 1, 2, and 4 days post-op.] |
| Determine the Number of Participants With a Change of Local Toxicity in Tissues. (Outcome Discontinued) | Local toxicity will be determined by examining the osteochondral fragments obtained during the internal fixation surgery for cartilage and synovial histological changes. This outcome was discontinued. Samples were not taken and this measurement was not completed. | Pre-op baseline on the day before external fixation surgery (within 24 hours of injury), immediately post-op, and at 1, 2, and 4 days post-op. At the time of internal fixation (3-21 days after external fixation) and at 1, 2, and 4 days post-op. |
| Measure | Description | Time Frame |
|---|---|---|
| Patient Reported Outcome Measurement Information Systems (PROMIS) - Pain Interference | Pain Interference scale. Higher scores indicate greater pain interference (worse score). Result is reported as a T-score, with the population norm at 50 and a standard deviation of 10. | 3, 6, 12, and 24 months |
| Patient Reported Outcome Measurement Information Systems (PROMIS) Physical Function |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Iowa | Iowa City | Iowa | 52240 | United States |
De-identified radiographic and clinical data will be shared.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase I Single Amobarbital/Gel-One Dose | Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II. amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 1, 2022 |
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Phase I: 6 patients will be treated with single dose open label, and safety measures will be assessed.
Phase IIa: Once initial safety is confirmed, 20 amobarbital:10 control patients will be treated with the single dose at the initial operation. Patients and attending surgeons will be blinded to the identity of the dose. Assuming continued safety, an additional 20 amobarbital: 10 control patients will be treated with two doses and evaluated. The second dose of 2.5 mM amobarbital will be administered during the second operation.
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| Placebo (single dose) | Drug | One dose of placebo during the initial surgical intervention |
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| amobarbital/Gel-One (two doses) | Drug | One dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention. |
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| Placebo (two doses) | Drug | One dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention. |
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Physical Function - T-score - mean of 50 and a standard deviation (SD) of 10. Therefore a person with a T-score of 40 is one SD below the mean. Higher is better. |
| 3, 6, 12 and 24 month follow-up visit |
| Patient Reported Outcome Measurement Information Systems (PROMIS) Global Health Questionnaires - Mental Health and Physical Health Scores | Global Health - T-score - mean of 50 and a standard deviation (SD) of 10. Therefore a person with a T-score of 40 is one SD below the mean. Higher is better. | 6, 12 and 24 month follow-up |
| American Orthopaedic Foot and Ankle Society (AOFAS) Score. | 0-100 point scale with 100 perfect ankle function | 6,12 and 24 month follow-up |
| Foot and Ankle Disability Index (FADI). ADL and Sports Scores | Description: Results are reported on a percentage scale with 100% perfect (higher is better) | 6, 12 and 24 month follow-up |
| CT-based Fracture Energy | Fracture energy is measured in Joules. It is from CT data and measured computationally. It is a continuous measure - Higher Joules = more energy = worse fracture | calculated at 6 month follow-up |
| CT-based Contact Stress | Vertical CT scan of ankle are segmented and analyzed using finite element analysis. Results are expressed as Contract Stress Exposure (MPa) across areas. Scans were completed in 4 participants at baseline, 4 participants at 6 month visit, 1 participant at month 12 and 1 participant at month 24. Contact stress measurements were not completed on any scans and are not avaialble. | 6, 12 and 24 month follow-up |
| CT-based Joint Space Width | Vertical CT scan of ankle used to measure Joint Space Width at several locations to measure distance to calculate the mean tibiotalar joint space (mm). | Month 0, 6, 12 |
| FG001 |
| Phase IIa Part 1 Amobarbital/Gel-One Dose |
20 subjects will be randomized to amobarbital/Gel-One single dose. amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention |
| FG002 | Phase IIa Part 1 Placebo | 10 subjects will be randomized to amobarbital/Gel-One single dose. Placebo (single dose): One dose of placebo during the initial surgical intervention |
| FG003 | Phase IIa Part 2 Amobarbital/Gel-One Dose | 20 subjects will be randomized to one dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention. amobarbital/Gel-One (two doses): One dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention. |
| FG004 | Phase IIa Part 2 Placebo | 20 subjects will be randomized to one dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention. Placebo (two doses): One dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention. |
| COMPLETED |
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| NOT COMPLETED |
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The study ended after Phase I. No patients were enrolled to later phases.
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase I Single Amobarbital/Gel-One Dose | Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II. amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention |
| BG001 | Phase IIa Part 1 Amobarbital/Gel-One Dose | 20 subjects will be randomized to amobarbital/Gel-One single dose. amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention |
| BG002 | Phase IIa Part 1 Placebo | 10 subjects will be randomized to amobarbital/Gel-One single dose. Placebo (single dose): One dose of placebo during the initial surgical intervention |
| BG003 | Phase IIa Part 2 Amobarbital/Gel-One Dose | 20 subjects will be randomized to one dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention. amobarbital/Gel-One (two doses): One dose of amobarbital/Gel-One during the initial surgical intervention. A second dose will be administered during the second surgical intervention. |
| BG004 | Phase IIa Part 2 Placebo | 20 subjects will be randomized to one dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention. Placebo (two doses): One dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| BMI | Mean | Standard Deviation | kg/m2 |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Systemic Adverse Events Defined as Abnormal Laboratory Values and Number Where Amobarbital is Detected Systemically | Safety Measures: CBC and standard clinical chemistry assays to quantify circulating, ALT, AST, Bilirubin, Creatinine, and BUN and the measurement of urine protein content will be evaluated and the number of participants with clinically significant abnormal laboratory values will be determined. Presence of amobarbital will be tested in blood and urine samples and the number of subjects it is detected in will be reported. | Posted | Count of Participants | Participants | Pre-op baseline on the day before external fixation surgery (within 24 hours of injury), immediately post-op, and at 1, 2, and 4 days post-op. At the time of internal fixation (3-21 days after external fixation) and at 1, 2, and 4 days post-op.] |
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| Primary | Determine the Number of Participants With a Change of Local Toxicity in Tissues. (Outcome Discontinued) | Local toxicity will be determined by examining the osteochondral fragments obtained during the internal fixation surgery for cartilage and synovial histological changes. This outcome was discontinued. Samples were not taken and this measurement was not completed. | Samples were not taken and this measurement was not completed | Posted | Count of Participants | Participants | Pre-op baseline on the day before external fixation surgery (within 24 hours of injury), immediately post-op, and at 1, 2, and 4 days post-op. At the time of internal fixation (3-21 days after external fixation) and at 1, 2, and 4 days post-op. |
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| Secondary | Patient Reported Outcome Measurement Information Systems (PROMIS) - Pain Interference | Pain Interference scale. Higher scores indicate greater pain interference (worse score). Result is reported as a T-score, with the population norm at 50 and a standard deviation of 10. | Only 1 participant had completed PROMIS PI at the 12 month follow-up visit, and none completed this for the 24 month follow-up visit. | Posted | Mean | Standard Deviation | t-score | 3, 6, 12, and 24 months |
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| Secondary | Patient Reported Outcome Measurement Information Systems (PROMIS) Physical Function | Physical Function - T-score - mean of 50 and a standard deviation (SD) of 10. Therefore a person with a T-score of 40 is one SD below the mean. Higher is better. | Only one participant completed PROMIS - Physical Function at 12 month follow-up and none have completed it at a 24 month follow-up visit. | Posted | Mean | Standard Deviation | score on a scale | 3, 6, 12 and 24 month follow-up visit |
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| Secondary | Patient Reported Outcome Measurement Information Systems (PROMIS) Global Health Questionnaires - Mental Health and Physical Health Scores | Global Health - T-score - mean of 50 and a standard deviation (SD) of 10. Therefore a person with a T-score of 40 is one SD below the mean. Higher is better. | Only one participant completed PROMIS Global Health Questionnaire at 12 month follow-up visit, and none completed it at 24 month visit. Higher scores are better | Posted | Mean | Standard Deviation | score on a scale | 6, 12 and 24 month follow-up |
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| Secondary | American Orthopaedic Foot and Ankle Society (AOFAS) Score. | 0-100 point scale with 100 perfect ankle function | Only one participant had AOFAS collected at 12 months and none at month 24. | Posted | Mean | Standard Deviation | score on a scale | 6,12 and 24 month follow-up |
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| Secondary | Foot and Ankle Disability Index (FADI). ADL and Sports Scores | Description: Results are reported on a percentage scale with 100% perfect (higher is better) | Only one participant completed Month 12 and no participants completed this questionnaire at month 24 | Posted | Mean | Standard Deviation | score on a scale | 6, 12 and 24 month follow-up |
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| Secondary | CT-based Fracture Energy | Fracture energy is measured in Joules. It is from CT data and measured computationally. It is a continuous measure - Higher Joules = more energy = worse fracture | Posted | Mean | Full Range | Joules | calculated at 6 month follow-up |
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| Secondary | CT-based Contact Stress | Vertical CT scan of ankle are segmented and analyzed using finite element analysis. Results are expressed as Contract Stress Exposure (MPa) across areas. Scans were completed in 4 participants at baseline, 4 participants at 6 month visit, 1 participant at month 12 and 1 participant at month 24. Contact stress measurements were not completed on any scans and are not avaialble. | Phase I participants who underwent Vertical CT ankle scans. Because of delays, final followups of the subjects were completed after funding was gone. At the time of those follow ups there had been planned budgeted CT's which would be the source material for CS measures. Because of the small number of pts it was felt the only information that was useful scientifically was for safety. Since contact stress would not contribute to that outcome a decision was made to not pay of those scans. | Posted | Number | mPA | 6, 12 and 24 month follow-up |
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| Secondary | CT-based Joint Space Width | Vertical CT scan of ankle used to measure Joint Space Width at several locations to measure distance to calculate the mean tibiotalar joint space (mm). | Mean Joint Space Width | Posted | Mean | Full Range | mm | Month 0, 6, 12 |
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Adverse event information was assessed immediately post Open Reduction and Internal Fixation (ORIF) surgery, and at 1 and 2 days post-ORIF. This was also assessed at each follow-up visit. This included the first clinic follow-up visit (approximately 2 weeks post ORIF) and at the 3, 6, 12 and 24 month follow-up visits.
Information regarding adverse events collected at study visits.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase I Single Amobarbital/Gel-One Dose | Phase I: An open label study of 3 patients will be done. If no dose limiting toxic (DLT) side effects occur, then an additional 3 patients will be done. If no DLT events occur, the study will proceed to Phase II. amobarbital/Gel-One (one dose): One dose of amobarbital/Gel-One during the initial surgical intervention | 0 | 5 | 0 | 5 | 0 | 5 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Research Associate | University of Iowa | 319-384-5101 | ashley-kochuyt@uiowa.edu |
| Apr 1, 2026 |
| Prot_SAP_004.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 17, 2022 | Apr 1, 2026 | ICF_005.pdf |
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| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| >=65 years |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Title | Measurements |
|---|---|
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| Abnormal CBC Result |
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| Abnormal Urine Protein |
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