Overview
Rehabilitation of knee stability and function after anterior cruciate ligament (ACL) reconstruction is slow and costly. The use of anabolic steroids, such as oxandrolone, may aid in the recovery of muscle mass and strength, as well as functional capacity. Oxandrolone, derived from dihydrotestosterone, has high anabolic activity and low androgenic activity (a 13:1 ratio), making it more effective in promoting weight gain with fewer side effects compared to other steroids. Registered by the FDA and previously by ANVISA (National Health Surveillance Agency (Brazil), it is indicated for cases of post-trauma or post-surgery weight loss. The subdermal use of oxandrolone implants is proposed to release the drug directly into the bloodstream, improving efficacy and reducing issues related to oral administration. This study evaluates the safety and tolerability of the absorbable subdermal oxandrolone implant for 24 weeks versus placebo implant in both men and women as an adjuvant treatment during rehabilitation following anterior cruciate ligament (ACL) surgical reconstruction. The serum and pharmacokinetic profile of the oxandrolone implant will be monitored.
Description
This is a phase II, randomized, double-blind, placebo-controlled, multicenter clinical study designed to evaluate the safety and tolerability profile of the absorbable oxandrolone implant as an adjuvant treatment in rehabilitation following anterior cruciate ligament (ACL) reconstruction surgery. The primary safety outcome will be the incidence of serious adverse events (SAEs) collected through spontaneous reports and/or clinical findings over 24 weeks after randomization (subdermal insertion of the absorbable oxandrolone implant). The exploratory evaluation of the efficacy of the absorbable oxandrolone implant will compare the use of oxandrolone implant with a placebo pellet in the rehabilitation of patients after ACL reconstruction surgery will be based on its effects on muscle mass recovery, muscle strength, and functional capacity.
Eligibility
Inclusion Criteria:
- Men and women aged between 18 and 45 years old
- Body weight between 50-110 kg for men and 40-90 kg for women
- BMI ≤30
- Complete rupture of the ACL as visualized by pre-operative magnetic resonance imaging
- Pre-operative radiographic examination with normal joint condition
- Having undergone knee arthroscopy surgery for anterior cruciate ligament reconstruction using autologous hamstring tendon graft
- No other associated injuries, such as posterior cruciate ligament (PCL) injury, grade III medial collateral ligament (MCL) injury, or severe concomitant injury in the contralateral knee (LCL)
- Very active, active, or irregularly active classification of type A or B by the International Physical Activity Questionnaire (IPAQ)
- Continuation of meeting all inclusion criteria verified at the Screening Visit (SV/V1).
- Adherence to the rehabilitation protocol, having participated in at least 10 physical therapy sessions since the SV/V1.
- Functional range of motion from 0 to 120º and ability to walk without the aid of crutches.
- Sitting blood pressure in the clinic \<180/95 mmHg.
- Hematocrit ≤ 50%.
- ALT less than three times the upper limit of normal.
- Serum creatinine \<2 mg/dl.
- Bilirubin \< 3.0 mg/dl.
- Albumin \<3 g/dl or prealbumin \<10 mg/dl.
- PSA ≤ 4.1 ng/ml (men only).
Exclusion Criteria:
- Only for female participants:
- Confirmed or suspected pregnancy
- History of childbirth, miscarriage, or lactation within the past 3 months
- Refusal to use permitted contraceptive methods during the study and for 90 days after study completion, unless surgically sterile or expressly declaring to be at no risk of pregnancy due to abstinence or non-reproductive sexual practices
- Clinical signs of hyperandrogenism
- Polycystic Ovary Syndrome (PCOS)
- Known or suspected breast carcinoma
Only for male participants:
-Known or suspected prostate or male breast carcinoma
For both male and female participants:
- Previous severe injury or history of surgery on the lower limbs
- Knee injury older than 12 months
- Unstable longitudinal meniscal tear
- Meniscus suture during ACL surgical reconstruction
- Use of patellar, quadriceps, or any graft other than hamstring tendon during ACL surgical reconstruction
- Known contraindication to hormone use
- Any condition that worsens with hormonal treatment
- Personal history of deep vein thrombosis (DVT)
- Known coagulopathy
- Known chromosomal disorders
- Hypersensitivity to anabolic androgenic steroids
- Previous failure of oxandrolone treatment
- Use of testosterone (or analogs) and other anabolic androgenic steroids in any pharmaceutical form within the last 3 months
- Pituitary tumor
- Creatinine levels \>2 mg/dl or history of chronic kidney disease
- Myocardial infarction within the last 6 months
- Uncontrolled dyslipidemia
- Uncontrolled diabetes
- Patients with chronic obstructive pulmonary disease (COPD) not responsive to bronchodilators
- Any contraindication to undergoing magnetic resonance imaging (MRI)
- Claustrophobia
- Sedentary classification according to the International Physical Activity Questionnaire (IPAQ)
- High-performance athlete
- Known psychiatric diagnosis, including major or persistent depressive disorder, bipolar disorder, anxiety disorders, social phobia, specific phobias, obsessive-compulsive disorder, psychotic disorders, personality disorders, eating disorders, neurocognitive disorders, developmental disorders, or somatoform disorders (somatization or hypochondriasis)
- Presence of urinary disorders
- Known diagnosis of fibromyalgia
- Current smoking
- History of drug abuse
- Participation in other clinical trial protocols within the past 30 days
- Participant who, in the investigator's opinion, presents other conditions or clinical/laboratory abnormalities that make them unsuitable to participate in the study.