Clinical trial NCT06974526: Subdermal Implant-bioabsorbable Oxandrolone Pellet For Rehabilitation Following Anterior Cruciate Ligament (ACL) Surgical Reconstruction
Official title: Randomized, Multicenter, Double-blind, Parallel, Placebo-controlled Study to Investigate the Safety and Exploratory Efficacy of the Absorbable Oxandrolone Implant as an Adjuvant Treatment in Rehabilitation Following Anterior Cruciate Ligament (ACL) Surgical Reconstruction (IMOX Study)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Anterior Cruciate Ligament (ACL) Reconstruction
Keywords: Anterior cruciate ligament (ACL)
Oxandrolone
Absorbable subdermal implant
Adverse effects
Lead sponsor: Science Valley Research Institute
Sponsor class: OTHER
Collaborators: name: Stin Pharma
First posted: 2025-05-16
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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 criteria: 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.

Primary outcomes:
measure: Combination of serious adverse events (SAEs) accumulated within 24 weeks of oxandrolone or placebo pellet insertion and collected through spontaneous reporting and/or clinical findings
timeFrame: From randomization to the end of study on Week 24.
Secondary outcomes:
measure: Biochemical Profile
timeFrame: At pre-insertion, 4, 12, and 24 weeks after randomization
measure: Metabolic Profile
timeFrame: At pre-insertion, 4, 12, and 24 weeks after randomization
measure: Hormonal Profile
timeFrame: At pre-insertion, 4, 12, and 24 weeks after randomization
measure: Hemostasis Parameters
timeFrame: At pre-insertion, 4, 12, and 24 weeks after randomization
measure: Total serum oxandrolone concentration
timeFrame: Pre-insertion of the oxandrolone implant; various times after the insertion of the oxandrolone implant and 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.
measure: Area under the curve (AUC(0 ∞))
timeFrame: Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.
measure: Maximum concentration (Cmax)
timeFrame: Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.
measure: Time to reach maximum concentration (tmax)
timeFrame: Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.
measure: Half Life (t1/2)
timeFrame: Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.
Other outcomes:
measure: Changes in body composition
timeFrame: At pre-insertion and 12 and 24 weeks after randomization
measure: Changes in maximal muscle strength using isometric dynamometry
timeFrame: At pre-insertion, 12 and 24 weeks after randomization
measure: Changes in the Short Form Health Survey SF-36 Quality of Life Questionnaire
timeFrame: At pre-insertion, 12 and 24 weeks after randomization
measure: Changes in the General Anxiety Disorder Questionnaire (GAD-7)
timeFrame: At pre-insertion, 12 and 24 weeks after randomization
measure: Changes in the Patient Health Questionnaire (PHQ-9)
timeFrame: At pre-insertion, 12 and 24 weeks after randomization
measure: Changes in the Patient Acceptable Symptom State (PAS)
timeFrame: At pre-insertion, 12 and 24 weeks after randomization
measure: Changes in the Knee Society Score (KSS)
timeFrame: At pre-insertion, 12 and 24 weeks after randomization
measure: Changes in the Y Balance Test
timeFrame: 12 and 24 weeks after randomization
measure: Changes in the Lysholm Knee Scoring Scale
timeFrame: At pre-insertion, 12 and 24 weeks after randomization
Locations:
city: São Paulo
country: Brazil
facility: Science Valley Research Institute, São Paulo, Sao Paulo
state: Sao Paulo
Study officials:
affiliation: Hospital do Rocio
name: Roberto Tauchmann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bakowski P, Bakowska-Zywicka K, Piontek T. Clinical practice and postoperative rehabilitation after knee arthroscopy vary according to surgeons' expertise: a survey among polish arthroscopy society members. BMC Musculoskelet Disord. 2020 Sep 23;21(1):626. doi: 10.1186/s12891-020-03649-9.