Efficacy of Testosterone Gel to Restore Normal Serum Values of Testosterone During the Acute Phase of Critical Illness in Adult ICU Patients

Functional Disability After ICU Clinical Trial

— TestICUs  

Official title:

Efficacy of Testosterone Gel to Restore Normal Serum Values of Testosterone During the Acute Phase of Critical Illness in Adult ICU Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03678233
• Other study ID #: CHU-404
• Secondary ID: 2017-004978-34
• Status: Recruiting
• Phase: Phase 2
• Start date: June 27, 2019
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2023
• Source: University Hospital, Clermont-Ferrand
• Contact: Lise LACLAUTRE
• Phone: 04 73 75 49 63
• Email: drci[@]chu-clermontferrand.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Functional Disability After ICU
• Hypermetabolism in ICU
• Hypogonadism
• ICU Acquired Hypogonadism
• Loss of Muscle Mass
• Treatment With Testosterone Gel in ICU

Intervention

Drug:
• AndroGel 16.2 mg/L
Testosterone gel 1.62 % will be applied to upper arms or shoulders once a day at 9:00 am to dry and intact skin for a period of 28 days or until ICU discharge. The daily dose 101.25 mg in men and 20.25 mg in women.

Locations

Country	Name	City	State
France	Chu Clermont-Ferrand	Clermont-Ferrand

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

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* Note: There are 81 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pourcentage of patients with normal median value of serum total testosterone	Pourcentage of patients with median value of serum total testosterone collected from blood samples at day 4, 7, 10, 14 higher than 280 ng/dl in men and 12 ng/dl in women.	day 4 to day 14
Secondary	Proportion of patients with normal median free testosterone serum values	Proportion of patients with median free testosterone serum values at day 4, 7, 10, 14 higher than 58 pg/ml in men and 0,9 ng/ml in women	day 4 to day 14
Secondary	Proportion of patients with normal median serum values of bioavailable testosterone	Proportion of patients with median serum values of bioavailable testosterone at day 4, 7, 10, 14 higher than 75 ng/dl in men 0.8 ng/dl in women	day 4 to day 14
Secondary	Nitrogen balance	Daily and cumulative nitrogen balance from day 1 to extubation	daily from day 1 to day 14
Secondary	Physical performance	Physical performance by Six-minute walk test (6MWT)	day 14, 1month and 3 months after ICU discharge
Secondary	Muscle strength	Muscle strength by MRC (Medical Research Scale)	at ICU discharge, 1month and 3 months after ICU discharge
Secondary	Near Infrared Spectroscopy	Near Infrared Spectroscopy by NIRS test	at 14 days
Secondary	Muscular mass	Muscular mass by L3 computed tomography	at ICU discharge and 1month after ICU discharge
Secondary	Lung function	Lung function by spirometry	at 1 and 3 months after ICU discharge