Clinical Trial Finder

Translating Metabolic Responses to Mechanical Insult Into Early Interventions to Prevent PTOA

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

 No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

 Interventional
Eligible Ages 18 Years - 60 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Age 18-60 years.
  • - Acute closed or type 1 open ankle fractures (classified as OTA/AO 43 B 1-3 and 43 C 1- 3 or classified as 42 B and C fractures with 25% talar displacement and one of the following; syndesmosis injury or medial malleolar fracture at or above the shoulder) (Marsh et al.
, 2007)) without operative ipsilateral extremity trauma.
  • - Posterior malleolar and supination adduction rotational fractures that have an articular fracture line across the articular surface of the distal tibia.
Posterior malleolar fractures should affect 25% of the articular surface or greater.
  • - Fractures must have initial treatment within 72 hours of injury including initial injection of amobarbital or placebo.

Exclusion Criteria:

  • - Diabetes.
  • - Pregnant or nursing mothers and individuals with child-bearing potential that are not using birth control methods with >99% efficacy.
  • - Allergy to poultry products or cinnamon.
  • - Previous injuries to the ankle.
  • - High grade open wounds.
  • - Pre-existing immunologic or hematologic diseases.
  • - Pre-existing ankle arthritis.
  • - Ipsilateral fractures.
  • - Associated injuries that preclude standard rehabilitation.
- Pre-existing dysfunction of the kidneys, liver, blood, immune system, endocrine system (excluding diabetes) - Serum creatinine >/= 1.4 mg/dl; BUN > 30 mg/dl; ALT >/= 60 IU/L in males and >/= 50 IU/L in females; AST >/= 45 IU/L in males and > 40 IU/L in females; bilirubin > 1.3 mg/dL; platelets 200 mg/dL

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

 NCT04589611
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

 Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

 J L Marsh
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

 N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

 Other, U.S. Fed
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

 Osteoarthritis, Post-traumatic Osteoarthritis
Additional Details

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

Arms & Interventions

Arms

Experimental: 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.

Active Comparator: Phase IIa Part 1 amobarbital/Gel-One dose

20 subjects will be randomized to amobarbital/Gel-One single dose.

Placebo Comparator: Phase IIa Part 1 Placebo

10 subjects will be randomized to amobarbital/Gel-One single dose.

Active Comparator: 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.

Placebo Comparator: 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.

Interventions

Drug: - amobarbital/Gel-One (one dose)

One dose of amobarbital/Gel-One during the initial surgical intervention

Drug: - Placebo (single dose)

One dose of placebo during the initial surgical intervention

Drug: - 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.

Drug: - Placebo (two doses)

One dose of placebo during the initial surgical intervention. A second dose will be administered during the second surgical intervention.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Iowa, Iowa City, Iowa

Status

Recruiting

Address

University of Iowa

Iowa City, Iowa, 52240

Powered By