Placebo Versus Oxandrolone Supplementation in Trauma
Primary Purpose
Trauma Injury
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Oxandrolone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Trauma Injury
Eligibility Criteria
Inclusion Criteria:
- Male
- Ages 18-55 [inclusive]
- Skeletally-mature as based upon tibial or femoral physeal closure41
- Fracture of the femur or tibia treated with open reduction and internal fixation (simple articular patterns allowed).
- High energy injuries with associated local soft tissue damage. -
Exclusion Criteria:
- Unable to participate in rehabilitation including severe head injury, pre-existing TBI or cognitive dysfunction (stroke, dementia, documented developmental delay), patients with significant spinal cord injury or pre-accident paralytic injury or condition will beessential treatment in both intervention and control groups.
- Medically unfit for anabolic steroid treatment including those with active malignancy, concurrent prednisone use, elevated liver enzymes at baseline (baseline bloodwork to include LFT)
- Fracture due to primary or metastatic bone lesion
- Any contraindications to MRI.
- Patients with major psychiatric illness [trauma presentation for suicide attempts] and incarcerated patients will be excluded as they may lack autonomy, decision-making capacity and the ability to meet follow-ups.
- Patients with substance use disorders, due to increased abuse potential and possible baseline hepatic injury.
- Patients who are on blood thinning medication, at baseline.
- Patients receiving hormone treatment.
- Patients with active cancers.
Patients with a history of hypercalcemia/parathyroid disease and chronic renal disease.
-
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Oxandrolone
Placebo
Arm Description
Participants will be randomly assigned in a 1:1 fashion to one of the two treatment arms using the REDCap database randomization procedure.
Participants will be randomly assigned in a 1:1 fashion to one of the two treatment arms using the REDCap database randomization procedure.
Outcomes
Primary Outcome Measures
Delta volumetric vastus medialis diameter on MRI
MRI is taken to assess the vastus medialis muscle mass.
Secondary Outcome Measures
Delta volumetric thigh muscle mass on MRI
Delta volumetric thigh muscle mass on MRI at 52 week Post treatment and the VMO (Vastus Medialis) at 26 week visit.
Functional measure: 6-minute walk test
Activity count by ActiGraph GT3X-BT
The actigraph measures sleep efficiency.
Short Form 36 Health Survey
The minimum score is 0, and maximum score is 5.
Patient-Reported Outcomes Measurement Information System (PROMIS)
The minimum score is 0, and maximum score is 10.
Standard AP and Lateral X-Rays
Time to radiographic union of fracture in weeks based on bridging callous of 3 of 4 cortices on standard AP and lateral x-rays
Length of in-patient Acute Hospital stay, and Rehabilitation stay
Length of in-patient Acute Hospital stay, and Rehabilitation stay to be determined by the orthopedic surgeon.
MARX Scale
The minimum score is 0, and maximum score is 10.
VAS Score
The minimum score is 0, and maximum score is 10.
Hand-Held Dynamometer
The hand-held dynamometer is a small device that fits in the examiner's hand and is placed at precise locations on a subject's limb in an effort to assess the force generated by various muscles or groups of muscles.The minimum score is 0, and maximum score is 10.
Full Information
NCT ID
NCT05516849
First Posted
August 16, 2022
Last Updated
August 8, 2023
Sponsor
Sunnybrook Health Sciences Centre
Collaborators
United States Department of Defense, Walter Reed National Military Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT05516849
Brief Title
Placebo Versus Oxandrolone Supplementation in Trauma
Official Title
Placebo Versus Oxandrolone Supplementation in Trauma: A Randomized Multi-Center Double Blind Clinical Trial in High-Energy Lower Extremity Trauma (POST-Injury Trial)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Withdrawn
Why Stopped
FDA requested manufacturers of Oxandrolone Tablets, to voluntarily remove previously approved drug applications for Oxandrolone from the U.S. market & the funding decided to prematurely terminate the funding.
Study Start Date
May 19, 2022 (Anticipated)
Primary Completion Date
August 3, 2023 (Anticipated)
Study Completion Date
August 3, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sunnybrook Health Sciences Centre
Collaborators
United States Department of Defense, Walter Reed National Military Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary aim of this study is to examine the effect of Oxandrolone supplementation after lower extremity high energy fracture on muscle volume recovery. As Oxandrolone supplementation has never been examined in this patient population, the primary null hypothesis is that there will be no difference in measured thigh muscle mass volume between Oxandrolone supplementation and placebo administration groups.
Detailed Description
Lower extremity fractures associated with high-energy mechanisms of injury (combat injuries including blast or crush injuries, motor vehicle accidents, fall from significant height, gunshot injuries) are unfortunately common among active service members and civilians presenting to level-1 trauma centers worldwide. High-energy fractures have several unique characteristics that distinguish them from low-energy injuries. They typically occur in predominately younger, male patients (30-65 years old)1 and involve significant soft-tissue stripping or damage. These patients require at least one major reconstructive surgery, with the majority requiring multiple reconstructive surgeries, each associated with additional soft tissue injury and subsequent prolonged immobilization to facilitate limb stabilization. Despite extended rehabilitation focused on neuromuscular retraining and muscular development, the result is often permanent limitations of ambulation and medical retirement from active duty due to volumetric muscle loss. So, while advances in orthopedic approaches to fracture care have lowered complications such as non-union and malunion, rendering them less significant as limitations to restoring function soft-tissue complications now predominate.
Oxandrolone has been successfully utilized to accelerate muscular recovery, reduce muscle loss, and improve function in several populations including healthy elderly patients with frailty/sarcopenia, patients with large surface area burns, neuromuscular diseases, HIV, congenital heart disease and genetic diseases including Klinefelter's and Turner's Syndromes. In addition, Oxandrolone has also been safely used in pediatric patients to treat constitutionally delayed growth. Given the similarities in patient populations and the known limitations of volumetric muscle loss in military personnel and civilians after major trauma, Oxandrolone supplementation may reduce initial volumetric muscle loss and improve long-term muscle mass and function.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Trauma Injury
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomly assigned in a 1:1 fashion to one of the two treatment arms using a minimal sufficient randomization technique in REDCAP.
Masking
ParticipantInvestigator
Masking Description
All participants, clinicians, and staff will be blinded to the intervention groups. All patients with an adverse event will be reviewed by an onsite internal medicine affiliated with the study but not directly in recruitment or assessment of outcomes. Emergency unblinding will be allowed if participants present with an adverse event that in the opinion of consulting physicians is not explained by other causes AND knowing the treatment allocation will aid in the patient's management. The blind may be broken only with the permission of the Principal Investigator.
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Oxandrolone
Arm Type
Experimental
Arm Description
Participants will be randomly assigned in a 1:1 fashion to one of the two treatment arms using the REDCap database randomization procedure.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will be randomly assigned in a 1:1 fashion to one of the two treatment arms using the REDCap database randomization procedure.
Intervention Type
Drug
Intervention Name(s)
Oxandrolone
Intervention Description
Oxandrolone is a synthetic anabolic androgenic steroid that induces its responses by binding to androgen receptors which modulates gene expression to increase protein synthesis and efficient utilisation of amino acids. Oxandrolone was first synthesized in 1962 through 17alpha-alkylation of testosterone resulting in a formal composition of (4bS,7S,9aS,9bR,11aS)-tetradecahydro-7-hydroxy-4aS,6aS,7-trimethyl- cyclopentanaphthopyran-2(1H)-one and molecular formula of C19H30O3.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
As there is currently no approved medication to aid in soft-tissue regeneration, we will be using a placebo control.
Primary Outcome Measure Information:
Title
Delta volumetric vastus medialis diameter on MRI
Description
MRI is taken to assess the vastus medialis muscle mass.
Time Frame
upto 6 months
Secondary Outcome Measure Information:
Title
Delta volumetric thigh muscle mass on MRI
Description
Delta volumetric thigh muscle mass on MRI at 52 week Post treatment and the VMO (Vastus Medialis) at 26 week visit.
Time Frame
Up to 1 year
Title
Functional measure: 6-minute walk test
Time Frame
Up to 1 year
Title
Activity count by ActiGraph GT3X-BT
Description
The actigraph measures sleep efficiency.
Time Frame
Up to 1 year
Title
Short Form 36 Health Survey
Description
The minimum score is 0, and maximum score is 5.
Time Frame
Up to 1 year
Title
Patient-Reported Outcomes Measurement Information System (PROMIS)
Description
The minimum score is 0, and maximum score is 10.
Time Frame
Up to 1 year
Title
Standard AP and Lateral X-Rays
Description
Time to radiographic union of fracture in weeks based on bridging callous of 3 of 4 cortices on standard AP and lateral x-rays
Time Frame
Through study completion, an average of 1 year
Title
Length of in-patient Acute Hospital stay, and Rehabilitation stay
Description
Length of in-patient Acute Hospital stay, and Rehabilitation stay to be determined by the orthopedic surgeon.
Time Frame
Through study completion, an average of 1 year
Title
MARX Scale
Description
The minimum score is 0, and maximum score is 10.
Time Frame
Up to 1 year
Title
VAS Score
Description
The minimum score is 0, and maximum score is 10.
Time Frame
Up to 1 year
Title
Hand-Held Dynamometer
Description
The hand-held dynamometer is a small device that fits in the examiner's hand and is placed at precise locations on a subject's limb in an effort to assess the force generated by various muscles or groups of muscles.The minimum score is 0, and maximum score is 10.
Time Frame
Up to 1 year
10. Eligibility
Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male
Ages 18-55 [inclusive]
Skeletally-mature as based upon tibial or femoral physeal closure41
Fracture of the femur or tibia treated with open reduction and internal fixation (simple articular patterns allowed).
High energy injuries with associated local soft tissue damage. -
Exclusion Criteria:
Unable to participate in rehabilitation including severe head injury, pre-existing TBI or cognitive dysfunction (stroke, dementia, documented developmental delay), patients with significant spinal cord injury or pre-accident paralytic injury or condition will beessential treatment in both intervention and control groups.
Medically unfit for anabolic steroid treatment including those with active malignancy, concurrent prednisone use, elevated liver enzymes at baseline (baseline bloodwork to include LFT)
Fracture due to primary or metastatic bone lesion
Any contraindications to MRI.
Patients with major psychiatric illness [trauma presentation for suicide attempts] and incarcerated patients will be excluded as they may lack autonomy, decision-making capacity and the ability to meet follow-ups.
Patients with substance use disorders, due to increased abuse potential and possible baseline hepatic injury.
Patients who are on blood thinning medication, at baseline.
Patients receiving hormone treatment.
Patients with active cancers.
Patients with a history of hypercalcemia/parathyroid disease and chronic renal disease.
-
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Placebo Versus Oxandrolone Supplementation in Trauma
We'll reach out to this number within 24 hrs