NCT05825092 Effects of Early Testosterone Gel Administration on Physical Performance in the Critically Ill

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What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.

This trial targets 600 participants in total. It began in 2023-07-21 with a primary completion date of 2025-09-01.

Brief Summary

Critically ill patients experience major insults that lead to increased protein catabolism. Hypermetabolism occurs early and rapidly during the first week of critical illness to provide amino acids for the production of energy via gluconeogenesis, and also for the synthesis of acute phase proteins and repair of tissue damage. During acute phase, neuroendocrine and inflammatory responses promote protein breakdown and amino acid release. Under stress conditions, protein synthesis cannot match the increased rate of muscle proteolysis because of a state of anabolism resistance, which limits uptake of amino acids into muscles. Hypermetabolism results in a significant loss of lean body mass with an impact on weaning from the ventilator and muscle recovery. Functional disability can be long term sometimes with no full return to normal. In critically ill patients, severe and persistent testosterone deficiency is very common and is observed early after Intensive Care Unit (ICU) admission. This acquired hypogonadism promotes the persistent loss of skeletal muscle protein and is related to poor outcome. Administration of testosterone induces skeletal muscle fiber hypertrophy and decreases protein breakdown in healthy young men. It has been repeatedly shown that testosterone treatment enhances muscle mass and strength in hypogonadal men and women and can improve physical performance. Testosterone administration in burned patients reduces protein breakdown and increases protein synthesis efficiency. Oxandrolone, a synthetic testosterone analogue, reduces body mass and nitrogen loss and accelerates healing in burned patients. Trials in critically ill unburned patients failed to demonstrate any effect on clinical outcome but the studies were underpowered to detect a difference. Transdermal gel testosterone is the preferred route of administration for achieving steady serum testosterone concentrations as compared to oral and intramuscular formulations. Intramuscular injection induces strong fluctuations of testosterone plasma concentrations and can cause haematoma in patients with coagulation disorders, a common condition in ICUs. Several studies have raised the concern that testosterone administration could increase the risk of cardiovascular disease events. However, in a recent meta-analysis, no significant effects on cardiovascular risk were observed with either injected or transdermal testosterone supplementation in men, and the French National Agency for Medicines (ANSM) recently reported that drugs containing testosterone were not associated with an increased risk of cardiovascular events.

Eligibility Criteria

Inclusion Criteria: * Males and females aged over 18 years * Negative pregnancy test (b-HCG) in female patient of childbearing potential * Invasive mechanical ventilation expected to be required for more than 48 hours * Written informed consent obtained from the patient or his/her legal representative * Social security cover * Contraception * Female patient of childbearing potential (entering the study after a menstrual period and who has a negative pregnancy test), who agrees to use a highly effective method of contraception and an effective method of contraception by her male partner during treatment and for 7 months after the last treatment intake * Male patient with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an effective method of contraception by his female partner during treatment and for 4 months after the last treatment intake OR who agrees to use an effective method of contraception and a highly effective method of contraception by his female partner during the study and for 4 months after the last treatment intake Exclusion Criteria: * History of prostate cancer * History of breast cancer * Prostate cancer suspected or confirmed * Breast cancer suspected or confirmed * PSA (prostatic specific antigen) ≥ 4 ng/ml * ICU length of stay \> 120 h before enrollment * Moribund * Pre-existing illness with a life expectancy of \<6 months * Recent intracranial or spinal cord injury (\< 1 month) * Recent haemorrhagic or ischemic stroke (\< 1 month) * Neuromuscular disease * Cardiac arrest in non-shockable rhythm * Preexistent cognitive impairment or language barrier * Inability to walk without assistance prior to acute ICU illness (use of a cane or walkers not excluded) * Documented allergy to testosterone * Age \> 80 years * Pregnancy * Breast feeding

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