Evaluation of Testosterone Undecanoate on Muscle Strength and Mass in Hypogonadal Males Post-Bariatric Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to investigate the effect and clinical relevance of **testosterone therapy** combined with exercise and diet counselling in hypogonadal men undergoing bariatric surgery. This is clinically significant as it aims to address the potential benefits of testosterone replacement in improving outcomes related to muscle strength and mass, which are critical factors in the recovery and overall health of patients with **adipositas** and male hypogonadism.

Secondary objectives include evaluating the effect of testosterone therapy combined with exercise and diet counselling on various parameters such as muscle strength, body composition, hormones, components of the metabolic syndrome, inflammation, sexual function, and quality of life after weight loss in obese, hypogonadal men undergoing bariatric surgery. These assessments are crucial for understanding the broader impact of the therapy on metabolic and physiological health, as well as on the quality of life of the patients.

The clinical trial focuses on **adipositas** and male hypogonadism, specifically targeting a population of Caucasian men aged 18 to 60 years. Participants are required to have a body mass index (BMI) greater than 35 kg/m² with specific secondary diseases or a BMI greater than 40 kg/m² with significant health issues, as assessed by a multidisciplinary bariatric team. Additionally, eligible participants must have total testosterone levels below 12.0 nmol/l and no contraindications for testosterone treatment. The study does not include female subjects or vulnerable populations. The trial aims to evaluate the effect and clinical relevance of testosterone therapy combined with exercise and diet counseling in hypogonadal men undergoing bariatric surgery. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity habits.

The clinical trial is designed to evaluate the effect and clinical relevance of **testosterone** therapy combined with exercise and diet counseling in hypogonadal men undergoing bariatric surgery. This study is a randomized, placebo-controlled, and double-blind trial, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, thus minimizing bias. The trial is expected to run from August 1, 2018, to January 1, 2026, with a maximum treatment period of 112 days for each participant.

Participants will be required to attend several study visits throughout the trial. The initial visit will be a screening visit to determine eligibility based on criteria such as age, body mass index (BMI), and testosterone levels. Eligible participants are Caucasian men aged 18-60 years, with a BMI >35 kg/m² with specific secondary disease or BMI >40 kg/m² with significant health issues, and total testosterone levels below 12.0 nmol/l. There should be no contraindications for testosterone treatment. Following the screening, participants will be randomized to receive either the active treatment, Nebido 1000 mg solution for injection, or a placebo oily solution, both administered via intramuscular injection.

Subsequent follow-up visits will be scheduled to monitor the primary endpoint, which is the maximal isometric muscle strength in shoulder muscles. Secondary endpoints include assessments of regional body composition, physical strength, physical function, glucose metabolism, and coagulation/fibrinolysis status. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted to evaluate the outcomes of the intervention.

Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including adverse reactions to the treatment, withdrawal of consent, or any other medical reasons deemed necessary by the study investigators. The trial aims to provide additional information regarding the risk, benefit, and optimal use of testosterone therapy in this specific patient population.

The clinical trial involves the administration of **Nebido 1000 mg** solution for injection, which contains the active substance **testosterone undecanoate**. This experimental medication is provided in the form of a solution for injection and is administered via **intramuscular injection**. The dosage is set at a maximum daily dose of 14.28 mg, with a total maximum dose of 11,195 mg over the treatment period. The treatment duration is limited to 112 days. The pharmaceutical product is manufactured by Grünenthal GmbH and is not a pediatric formulation. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental medication, a **placebo** is used as a comparator treatment in this study. The placebo is an oily solution designed to mimic the testosterone undecanoate oily solution, with a concentration of 0.25 g/mL in a 4 mL ampoule, intended for intramuscular use. The placebo is utilized to maintain the double-blind nature of the study, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo does not contain any active pharmaceutical ingredients and serves to evaluate the efficacy and safety of the experimental treatment by comparison.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the measurement of maximal isometric muscle strength in the shoulder muscles, specifically shoulder elevation, expressed in Newtons (N). Secondary endpoints include a comprehensive evaluation of regional body composition using DXA scans, BMI, and waist/hip ratio. Additionally, physical strength will be assessed through maximal isometric muscle strength in the lower extremities (hip extension, hip abduction) and upper extremities (shoulder abduction, shoulder adduction). Physical function will be evaluated using performance-based measures such as the stair climb test and maximal oxygen uptake (VO2max). Further assessments will include glucose metabolism parameters like HOMA-R, HbA1c, and fasting plasma blood glucose, as well as coagulation/fibrinolysis status through thrombin generation measures.