Clinical trial NCT03678233: Efficacy of Testosterone Gel to Restore Normal Serum Values of Testosterone During the Acute Phase of Critical Illness in Adult ICU Patients
Official title: Efficacy of Testosterone Gel to Restore Normal Serum Values of Testosterone During the Acute Phase of Critical Illness in Adult ICU Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hypermetabolism in ICU
Loss of Muscle Mass
Functional Disability After ICU
ICU Acquired Hypogonadism
Treatment With Testosterone Gel in ICU
Keywords: hypermetabolism
hypogonadism
testosterone
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2018-09-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 may 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 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, decreases protein breakdown in healthy young men and burned patients. It has been repeatedly shown that testosterone treatment enhances muscle mass and strength in young and older hypogonadal men and women and can improve physical performance.

Detailed description: Type of trial

TestICUs-1 is a single center open-label parallel randomized controlled study phase II assessing the efficacy of testosterone gel to correct low testosterone serum levels associated with ICU acquired hypogonadism in mechanically ventilated patients with shock. TestICUs-1 will be conducted in the 10-bed medical ICU of the university hospital of Clermont-Ferrand. Study drug is Androgel® 1.62 mg/L approved by the ANSM for the treatment of hypogonadism in men containing 1.62% of testosterone.

Category of research Research involving human subjects aimed at assessing the efficacy of and safety to drug.

Study phase

* II/ Feasibility
* Technology Readiness Level : 7 B

A study assessing the efficacy of a multimodal strategy including treatment with testosterone gel, (75 mg/day in men and 25 mg/day in women) in improving physical activity in hemodialysis patients is in progress (Americano PHRC N 2012, AE Heng).

Eligibility criteria: Inclusion Criteria:

* - Males and females aged over 18 years receiving invasive mechanical ventilation
* Invasive mechanical ventilation expected to be required for more than 48 hours
* Treatment with vasoactive drugs
* Written informed consent obtained from the legal representative
* Social security cover

Exclusion Criteria:

* - History of prostate or breast cancer, prostatic specific antigen (PSA) ≥ 4 ng/ml
* ICU length of stay \> 72 h before enrollment
* Moribund defined as having a score SAPS II \> 75 12 hours after admission
* Pre-existing illness with a life expectancy of \<6 months
* Cardiac arrest
* Preexistent cognitive impairment or language barrier
* Acute intracranial or spinal cord injury
* Acute hemorrhagic or ischemic stroke
* Neuromuscular disease (Guillain-Barré, myasthenia)
* 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 or breast feeding
* Patient on judicial protection

Primary outcomes:
measure: Pourcentage of patients with normal median value of serum total testosterone
timeFrame: day 4 to day 14
Secondary outcomes:
measure: Proportion of patients with normal median free testosterone serum values
timeFrame: day 4 to day 14
measure: Proportion of patients with normal median serum values of bioavailable testosterone
timeFrame: day 4 to day 14
measure: Nitrogen balance
timeFrame: daily from day 1 to day 14
measure: Physical performance
timeFrame: day 14, 1month and 3 months after ICU discharge
measure: Muscle strength
timeFrame: at ICU discharge, 1month and 3 months after ICU discharge
measure: Near Infrared Spectroscopy
timeFrame: at 14 days
measure: Muscular mass
timeFrame: at ICU discharge and 1month after ICU discharge
measure: Lung function
timeFrame: at 1 and 3 months after ICU discharge
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Chu Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Konstantinos BACHOUMAS
role: PRINCIPAL_INVESTIGATOR
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