ACL Reconstruction, Muscle Atrophy, Osteoarthritis, Trauma
Conditions
Keywords
Testosterone, ACL Reconstruction, Clinical outcomes, Lean mass, Strength, Muscle atrophy
Brief summary
This study is being done to test whether taking testosterone can prevent loss of muscle mass and strength due to anterior cruciate ligament (ACL) reconstructive surgery. Testosterone is the principal male sex hormone and an anabolic (muscle promoting) steroid. It is essential for the development of male reproductive tissues and promotes increased muscle, bone mass, and the growth of body hair. The investigators hope to learn whether testosterone given before and after ACL reconstructive surgery will increase muscle mass and strength and potentially improve recovery time following surgery.
Detailed description
Overall Objective: The overall objective of this study is to determine if 8 weeks of testosterone first administered 2 weeks prior to surgery, can improve the outcome of anterior cruciate ligament (ACL) reconstruction. Overall Hypothesis: Standard-of-care rehabilitation with the addition of testosterone administration will augment muscle mass, strength, and physical function following ACL reconstructive surgery compared to standard rehabilitation alone. Significance: Muscle mass and strength are greatly reduced following ACL surgery. The investigators hypothesize that administration of testosterone will minimize these reductions or potentially increase muscle mass and strength. In doing so, testosterone may hasten a patient's return to physical activity. If testosterone improves recovery after ACL surgery, the same treatment may be used for other injuries that involve trauma and muscle atrophy. Furthermore, this study will examine the effect of trauma with or without testosterone on myogenic regulators in muscle tissue taken during ACL surgery-providing possible mechanistic insights for the clinical outcomes.
Interventions
DRUGTestosterone
8 weeks of testosterone administration beginning 2 weeks before ACL surgery
DRUGPlacebo
8 weeks of saline administration beginning 2 weeks before ACL surgery
Sponsors
Boston University
University of Oregon
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* A complete ACL tear as visualized on MRI * The ACL injury can be either isolated or combined with one or several of the following injuries visualized on MRI and/or arthroscopy: * a meniscus tear that is either left untreated or treated with a partial resection * a small, stable meniscus tear treated with fixation, but with the fixation not interfering with the rehabilitation protocol * cartilage changes verified on MRI with an arthroscopically determined intact surface. * A radiographic examination with normal joint status or combined with either one of the following findings: * a small-avulsed fragment located laterally, usually described as a Segond fracture, JSN grade 1 or osteophytes grade 1 as determined by the OARSI atlas15
Exclusion criteria
* Previous major knee injury or knee surgery * Associated posterior cruciate ligament (PCL) or medical collateral ligament (MCL) injury grade III * Concomitant severe injury to contra-lateral knee * Injury to the lateral/posterolateral ligament complex with significantly increased laxity * Unstable longitudinal meniscus tear that requires repair and where the following postoperative treatment (we.e. bracing and limited range of motion) interferes with the rehabilitation protocol * Bi-compartmental extensive meniscus resections * Cartilage injury representing a full thickness loss down to bone * Total rupture of MCL/LCL as visualized on MRI. * History of deep vein thrombosis (DVT) or a disorder of the coagulative system * Claustrophobia * Prior or current use of anabolic steroids * General systemic disease affecting physical function * Chromosomal disorders * Medications that interfere with testosterone production or function, including but not limited to 5α-reductase inhibitors * Any other condition or treatment interfering with the completion of the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Lean Mass | 6, 12, and 24 weeks post operative | Relative changes in lean mass from 2 weeks prior to surgery to 6 weeks, 12 weeks, and 24 weeks following surgery between the two groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| KOOS Scores | 6 weeks, 12 weeks, 24 weeks post surgery | Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) from 2 weeks prior to surgery to 6, 12, and 24 weeks post surgery. KOOS is scored from 0 to 100 with 0 representing extreme knee problems and 100 representing normal knee function. |
| Strength | 6, 12, and 24 weeks post surgery | Changes in muscle strength from the start of rehabilitation to 6, 12, and 24 weeks following surgery between the two groups in the injured limb. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Testosterone Testosterone: 8 weeks 200mg dose testosterone enanthate | 7 |
| Placebo Saline: Placebo for 8 weeks | 7 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Testosterone |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 14 Participants | 7 Participants |
| Age, Continuous | 26.2 years STANDARD_DEVIATION 4.1 | 28.2 years STANDARD_DEVIATION 6.7 | 30.4 years STANDARD_DEVIATION 9.3 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 7 participants | 14 participants | 7 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 0 / 7 | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
Changes in Lean Mass
Relative changes in lean mass from 2 weeks prior to surgery to 6 weeks, 12 weeks, and 24 weeks following surgery between the two groups.
Time frame: 6, 12, and 24 weeks post operative
Population: Region of enrollment from the Los Angeles area.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone | Changes in Lean Mass | 6 weeks post op | 2.8 kg | Standard Deviation 1.7 |
| Testosterone | Changes in Lean Mass | 12 weeks post op | 2.16 kg | Standard Deviation 3.48 |
| Testosterone | Changes in Lean Mass | 24 weeks post op | 2.13 kg | Standard Deviation 5.3 |
| Placebo | Changes in Lean Mass | 6 weeks post op | -0.1 kg | Standard Deviation 1.5 |
| Placebo | Changes in Lean Mass | 12 weeks post op | 0.01 kg | Standard Deviation 1.08 |
| Placebo | Changes in Lean Mass | 24 weeks post op | 1.05 kg | Standard Deviation 1.18 |
Comparison: Power was estimated for change in lean mass of 3.0 plus or minus 1.5 kg in healthy men receiving testosterone. Using a significance level of 0.05 and a power of 0.80, a sample size of 6 participants per group was calculated.~This statistical analysis applies to lean mass in participants 6 weeks post operative.p-value: 0.35Wilcoxon (Mann-Whitney)
Comparison: Power was estimated for change in lean mass of 3.0 plus or minus 1.5 kg in healthy men receiving testosterone. Using a significance level of 0.05 and a power of 0.80, a sample size of 6 participants per group was calculated.~This statistical analysis applies to lean mass in participants 12 weeks post operative.p-value: 0.48Wilcoxon (Mann-Whitney)
Comparison: Power was estimated for change in lean mass of 3.0 plus or minus 1.5 kg in healthy men receiving testosterone. Using a significance level of 0.05 and a power of 0.80, a sample size of 6 participants per group was calculated.~This statistical analysis applies to lean mass in participants 24 weeks post operative.p-value: 0.74Wilcoxon (Mann-Whitney)
Secondary
KOOS Scores
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) from 2 weeks prior to surgery to 6, 12, and 24 weeks post surgery. KOOS is scored from 0 to 100 with 0 representing extreme knee problems and 100 representing normal knee function.
Time frame: 6 weeks, 12 weeks, 24 weeks post surgery
Population: Region of enrollment from the Los Angeles area.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone | KOOS Scores | 6 weeks post op | 63.2 score on a scale | Standard Deviation 10.6 |
| Testosterone | KOOS Scores | 12 weeks post op | 76.7 score on a scale | Standard Deviation 9.9 |
| Testosterone | KOOS Scores | 24 weeks post op | 84 score on a scale | Standard Deviation 9.4 |
| Placebo | KOOS Scores | 6 weeks post op | 65.5 score on a scale | Standard Deviation 13 |
| Placebo | KOOS Scores | 12 weeks post op | 73.2 score on a scale | Standard Deviation 15 |
| Placebo | KOOS Scores | 24 weeks post op | 86.6 score on a scale | Standard Deviation 8.3 |
Secondary
Strength
Changes in muscle strength from the start of rehabilitation to 6, 12, and 24 weeks following surgery between the two groups in the injured limb.
Time frame: 6, 12, and 24 weeks post surgery
Population: Region of enrollment from the Los Angeles area.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone | Strength | 6 weeks post op | -53.5 Nm | Standard Deviation 35.8 |
| Testosterone | Strength | 12 weeks post op | -18.3 Nm | Standard Deviation 52.7 |
| Testosterone | Strength | 24 weeks post op | 19.2 Nm | Standard Deviation 60.9 |
| Placebo | Strength | 6 weeks post op | -33.4 Nm | Standard Deviation 37.4 |
| Placebo | Strength | 12 weeks post op | -6.6 Nm | Standard Deviation 40.3 |
| Placebo | Strength | 24 weeks post op | 19.0 Nm | Standard Deviation 33.9 |