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

NCT ID: NCT05825092

Last Updated: 2023-10-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

600 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-21

Study Completion Date

2027-04-01

Brief Summary

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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.

Detailed Description

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Conditions

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Critical Illness

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a prospective, phase II, multi-centre, double blind, randomised, controlled, parallel group study.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
double blind

Study Groups

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AndroGel® 1.62%

AndroGel® will be applied daily to the upper arms/shoulders. 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

Group Type ACTIVE_COMPARATOR

Androgel Topical Product

Intervention Type DRUG

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

Physical performance

Intervention Type DIAGNOSTIC_TEST

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

Muscle strength

Intervention Type DIAGNOSTIC_TEST

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)

Muscular mass

Intervention Type DIAGNOSTIC_TEST

Muscular mass at 3, 6 months and 1 year after ICU admission

Mid-arm muscle circumference (MAMC)

Test: Functional status

Intervention Type DIAGNOSTIC_TEST

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)

Oxygen muscular consumption

Intervention Type DIAGNOSTIC_TEST

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

Placebo gel will be the same gel without testosterone

Placebo gel will be applied daily to the upper arms/shoulders. 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 treatment or until hospital discharge

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Physical performance

Intervention Type DIAGNOSTIC_TEST

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

Muscle strength

Intervention Type DIAGNOSTIC_TEST

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)

Muscular mass

Intervention Type DIAGNOSTIC_TEST

Muscular mass at 3, 6 months and 1 year after ICU admission

Mid-arm muscle circumference (MAMC)

Test: Functional status

Intervention Type DIAGNOSTIC_TEST

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)

Oxygen muscular consumption

Intervention Type DIAGNOSTIC_TEST

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

Interventions

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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

Intervention Type 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

Intervention Type DRUG

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

Intervention Type 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)

Intervention Type DIAGNOSTIC_TEST

Muscular mass

Muscular mass at 3, 6 months and 1 year after ICU admission

Mid-arm muscle circumference (MAMC)

Intervention Type 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)

Intervention Type 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

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Androgel 1.62% Transdermal Gel

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Clermont-Ferrand

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Konstantinos BACHOUMAS, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital, La Roche sur Yon

Bertrand SOUWEINE, MD, PhD

Role: STUDY_DIRECTOR

University Hospital, Clermont-Ferrand

Locations

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Service de Medecine Intensive et Réanimation CHU de Bordeaux Hopital Pellegrin

Bordeaux, , France

Site Status NOT_YET_RECRUITING

Service d'Anesthésie et Réanimation Centre Jean-Perrin

Clermont-Ferrand, , France

Site Status RECRUITING

Service de Médecine Intensive et Réanimation (MIR), CHU Clermont-Ferrand

Clermont-Ferrand, , France

Site Status RECRUITING

Service de Médecine Intensive et de Réanimation CHD La Roche sur Yon

La Roche-sur-Yon, , France

Site Status RECRUITING

Service de Médecine Intensive et Réanimation CHU Nantes, Hôtel Dieux

Nantes, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Lise LACLAUTRE

Role: CONTACT

+33473754963

Facility Contacts

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Alexandre BOYER, MD

Role: primary

Alexandre LAUTRETTE

Role: primary

Claire DUPUIS, MD

Role: primary

Konstantinos Bachoumas, MD

Role: primary

Jean Reignier

Role: primary

Other Identifiers

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PHRC N 2018 BACHOUMAS

Identifier Type: -

Identifier Source: org_study_id

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