NCT05825092

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

Effects of Early Testosterone Gel Administration on Physical Performance in the Critically Ill: a Randomised Double Blind Clinical Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 600 (estimated)
• Sponsor: University Hospital, Clermont-Ferrand · Academic / Other
• Sex: All
• Age: 18 Years – 79 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Critical Illness

Interventions

Type	Name	Description
DRUG	Androgel Topical Product	AndroGel® will be applied daily to the upper arms/shoulders at 9:00 am. The daily dose will be 101.25 mg in men and 20.25 mg in women. AndroGel® will be administered within 24 hours after inclusion for a period of 28 days or until hospital discharge. For patients discharged from ICU before day 28, AndroGel® will be administered in hospital wards to complete the 28 days of treatment or until hospital discharge
DRUG	Placebo	Placebo gel will be applied daily to the upper arms/shoulders at 9:00 am. The daily dose will be 101.25 mg in men and 20.25 mg in women. Placebo gel will be administered within 24 hours after inclusion for a period of 28 days or until hospital discharge. For patients discharged from ICU before day 28, Placebo gel will be administered in hospital wards to complete the 28 days of
DIAGNOSTIC_TEST	Physical performance	Physical performance at 3, 6 months and 1 year after ICU admission 6 minute walk distance 3 months after ICU admission, at 6 months and at 1 year Percentage of patients with Short Physical Performance Battery \< 10 at 3, 6 months and 1 year Physical component of SF 36 (Medical Outcomes Study 36 Item Short Form Health Survey) at 3, 6 months and 1 year
DIAGNOSTIC_TEST	Muscle strength	Muscle strength at ICU discharge at 3, 6 months and 1 year after ICU admission Handgrip: Kg and percent of the predicted force Medical Research Council testing (MRC)
DIAGNOSTIC_TEST	Muscular mass	Muscular mass at 3, 6 months and 1 year after ICU admission Mid-arm muscle circumference (MAMC)
DIAGNOSTIC_TEST	Test: Functional status	Functional status at 3, 6 months and 1 year after ICU admission • Composite score of 11 items of Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL)
DIAGNOSTIC_TEST	Oxygen muscular consumption	Oxygen muscular consumption at ICU discharge and at 3 months after ICU admission Ventilation free days at day 28 Length of stay in ICU Length of stay in hospital Mortality rate at day 28 Mortality rate at day 90 ICU mortality rate Hospital mortality rate

Timeline

• Start date: 2023-07-21
• Primary completion: 2025-09-01
• Completion: 2027-04-01
• First posted: 2023-04-24
• Last updated: 2023-10-02

Locations

5 sites across 1 country: France