Placebo Versus Oxandrolone Supplementation in Trauma

Placebo Versus Oxandrolone Supplementation in Trauma: A Randomized Multi-Center Double Blind Clinical Trial in High-Energy Lower Extremity Trauma (POST-Injury Trial)

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.

Study Overview

• Status: Withdrawn
• Conditions: Trauma Injury
• Intervention / Treatment: Drug: Oxandrolone; Other: Placebo

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.

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male
2. Ages 18-55 [inclusive]
3. Skeletally-mature as based upon tibial or femoral physeal closure41
4. Fracture of the femur or tibia treated with open reduction and internal fixation (simple articular patterns allowed).
5. High energy injuries with associated local soft tissue damage. -

Exclusion Criteria:

1. 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.
2. Medically unfit for anabolic steroid treatment including those with active malignancy, concurrent prednisone use, elevated liver enzymes at baseline (baseline bloodwork to include LFT)
3. Fracture due to primary or metastatic bone lesion
4. Any contraindications to MRI.
5. 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.
6. Patients with substance use disorders, due to increased abuse potential and possible baseline hepatic injury.
7. Patients who are on blood thinning medication, at baseline.
8. Patients receiving hormone treatment.
9. Patients with active cancers.

10. Patients with a history of hypercalcemia/parathyroid disease and chronic renal disease.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxandrolone; Participants will be randomly assigned in a 1:1 fashion to one of the two treatment arms using the REDCap database randomization procedure.	Drug: Oxandrolone; 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.
Placebo Comparator: Placebo; Participants will be randomly assigned in a 1:1 fashion to one of the two treatment arms using the REDCap database randomization procedure.	Other: Placebo; As there is currently no approved medication to aid in soft-tissue regeneration, we will be using a placebo control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delta volumetric vastus medialis diameter on MRI	MRI is taken to assess the vastus medialis muscle mass.	upto 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 1 year
Functional measure: 6-minute walk test		Up to 1 year
Activity count by ActiGraph GT3X-BT	The actigraph measures sleep efficiency.	Up to 1 year
Short Form 36 Health Survey	The minimum score is 0, and maximum score is 5.	Up to 1 year
Patient-Reported Outcomes Measurement Information System (PROMIS)	The minimum score is 0, and maximum score is 10.	Up to 1 year
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	Through study completion, an average of 1 year
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.	Through study completion, an average of 1 year
MARX Scale	The minimum score is 0, and maximum score is 10.	Up to 1 year
VAS Score	The minimum score is 0, and maximum score is 10.	Up to 1 year
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.	Up to 1 year

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: United States Department of Defense; Walter Reed National Military Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): May 19, 2022
• Primary Completion (Estimated): August 3, 2023
• Study Completion (Estimated): August 3, 2023

Study Registration Dates

• First Submitted: August 16, 2022
• First Submitted That Met QC Criteria: August 24, 2022
• First Posted (Actual): August 26, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Anabolic Agents; Oxandrolone
• Other Study ID Numbers: 3822: POST-INJURY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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