Use of Testosterone to Prevent Post-Surgical Muscle Loss - Pilot Study

Study Overview
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Brief Summary
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The loss of muscle mass post-surgery confounds recovery efforts and leads to a delay in patient's ability to return to activities. Although the use of testosterone in aging and chronic muscle loss has been investigated, this study could prove short-term use of testosterone efficacious in preventing muscle atrophy due to surgery. We hypothesize that by bracketing an indexed knee surgery with testosterone undecanoate injections, post-surgical quadriceps muscle loss may be minimized. Determination of the effect of intra-muscular (IM) testosterone injections in preventing quadriceps muscle loss are measured by serial MRI and manual measurements of quadriceps cross-section.

Detailed Description
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This is an in vivo study using serial IM testosterone undeconate injections in participants undergoing knee surgery with limited weight bearing post-operatively which includes partial/total knee replacement, ACL reconstruction/revision, meniscal allograft transplantation and articular cartilage paste grafting. The design is a randomized, controlled, double blind, longitudinal study of intra-muscular injections of testosterone versus saline control. Pre-operative and post-operative assessments will include: serial MRIs and manual measurements of quadriceps cross-section and knee pain and function survey, KOOS. Blood analysis will be performed for therapeutic assessment and safety. The participant will receive two testosterone undeconate injections, once during their pre-operative visit and once during their 1 month visit. Timing of assessments will be pre-operative, 1-4 days post-operative and 1, 3, and 6 months. Measurement of the control group versus experimental group at all time points may identify differences in participant response to testosterone injections.

Official Title
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Use of Testosterone to Prevent Post-Surgical Muscle Loss - Pilot Study

Conditions
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Muscle Atrophy, Surgery, Knee Injuries and Disorders, Complication of Surgical Procedure, Trauma

Intervention / Treatment
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* Drug: Aveed 750 MG in 3 ML IM Injection
* Other: Normal Saline 3 ML IM Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males age 18-65. Undergoing significant knee surgery such as partial/total knee replacement, ligament reconstruction, meniscus surgeries or articular cartilage paste grafting. Exclusion Criteria: Men with carcinoma of the breast or known or suspected carcinoma of the prostate. Men with BMI > 30 and Type I or II diabetes diagnosis Men prone to deep vein thrombosis or sleep apnea. Men with pre-existing hematocrit abnormalities. Men with pre-existing cardiac, renal, hepatic disease. Men who are taking insulin, medicines that decrease blood clotting or corticosteroids. Men with known hypersensitivity to testosterone undecanoate or any of its formulation ingredients (testosterone, refined castor oil, benzyl benzoate). Subject's unable or unwilling to comply with the protocol. Subject's unable to provide informed consent. Subject's unable to understand verbal and/or written English.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Testosterone Group<br>Participants receiving two IM Testosterone injections. | Drug: Aveed 750 MG in 3 ML IM Injection<br>* Participants in the Testosterone Group will receive two IM Aveed injections 1 month apart.<br>|
| Placebo Comparator: Control Group<br>Participants receiving two IM Normal Saline Injections. | Other: Normal Saline 3 ML IM Injection<br>* Participants in the Control Group will receive two IM normal saline injections 1 month apart.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in MRI Cross Sectional Area of the Quadriceps | T1 Axial and Sagittal planes will be obtained using a ONI 1.0T extremity MRI. Axial Cross sectional Area (cm^2) will be measured of the Quadriceps muscle. | Pre-operative and 1, 3, and 6 months post-operative | 
| Change in Manual Measurements of the Quadriceps | Manual measurement of the quadriceps muscle will be performed 8-cm proximal to the superior-patella using a standard cm measuring tape. | Pre-operative and 1, 3, and 6 months post-operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Knee Pain and Function Survey, KOOS | Evaluate the knee pain and function of subjects as measures by the KOOS assessment. Sections: Pain Symptoms Activities of Daily Living Sports and Recreation Quality of Life Scoring: Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard. | Pre-operative and 1, 3, and 6 months post-operative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surgery, Testosterone, Muscle atrophy, Post-operative rehabilitation