Role of Anabolic Steroids on Intensive Care Unit-Acquired Weakness

Study Overview
=================
Brief Summary
-----------------
The researchers intend to investigate possible anabolic effects of bi-weekly exogenous testosterone administration during intensive care unit (ICU) stay for up to 8 weeks. Control group will receive standard ICU management and will also be followed during ICU stay.

Detailed Description
-----------------
For the study chronic critical patients will be included according to criterion of mechanical ventilation by orotracheal tube> 14 consecutive days or mechanical ventilation by tracheostomy> 8 consecutive days and that do not present exclusion criteria. Patients will be randomized into two follow-up groups: Intervention group with anabolic steroid and control group. The anabolic steroid intervention group will receive a bi-weekly dose of 200mg intramuscular testosterone cypionate and receive the standard treatment of nutritional therapy and physical therapy. While patients in the control group will receive only the standard treatment of nutrition and physical therapy, without addition of the anabolic drug. At the beginning of the study and weekly the patients will be evaluated in relation to the muscular profile with diaphragm ultrasound and Medical Research Council (MRC) application. In addition to the collection of serum homograms, leukogram, lipid profile and renal function tests. Weight and nutritional therapy-related data will be identified in the patient's chart regarding caloric and protein requirement and supply adequacy. In the inclusion and biweekly will be collected serum levels of free testosterone, blood count, leukogram, blood gas, renal function and liver function. Nitrogen balance of patients from urinary urea will be performed. The evaluations of the groups and the intervention with the anabolic steroid will be of 8 weeks or during the period of dependence of the mechanical ventilation. After this period the patients will be monitored for the outcome: length of stay in the intensive care unit, hospital stay until discharge and clinical outcome: death or discharge.

Official Title
-----------------
Pilot Randomized, Controlled Trial of Testosterone Therapy in Chronic Critically Ill Patients and Its Potential Effects on Weaning From Mechanical Ventilation and Intensive Care Unit-acquired Weakness

Conditions
-----------------
Critical Illness Polyneuropathies

Intervention / Treatment
-----------------
* Drug: Testosterone cypionate
* Other: Standard nutrition and physical therapy at ICU


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Individuals older than 18 years Mechanical ventilation by orotracheal tube for more than 14 consecutive days Mechanical ventilation by tracheostomy for more than 8 consecutive days Exclusion Criteria: End of life care Known hypersensitivity to formula Venous or arterial thrombosis within last 6 months: ischemic stroke, myocardial infarction, acute peripheral arterial occlusion, acute mesenteric ischemia, deep venous thromboembolism, pulmonary embolism Decompensated congestive heart failure Acute liver failure or acute on chronic liver failure Refractory shock (norepinephrine dose >0.3 mcg/kg/min or equivalent doses of any vasoactive agent) Platelets below <20,000 / mm3 without transfusion plan Personal history of prostate cancer Primary neuromuscular disorders such as myasthenia gravis, Guillain-Barré syndrome, amyotrophic lateral sclerosis, Duchenne Muscular dystrophy Current or prior spinal cord injury

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anabolic patients<br>Intramuscular injection of testosterone cypionate 200mg every 15 days in addition to standard nutrition and physical therapy at ICU. | Drug: Testosterone cypionate<br>* Bi-weekly intramuscular injection of testosterone cypionate 200mg.<br>* Other names: testosterone;Other: Standard nutrition and physical therapy at ICU<br>* follow-up of the patient without use of testosterone cypionate<br>|
| Other: Control<br>Standard nutrition and physical therapy at ICU without administration of testosterone cypionate | Other: Standard nutrition and physical therapy at ICU<br>* follow-up of the patient without use of testosterone cypionate<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical ventilation dependence | Days of any positive pressure ventilation described in the patient record from the start of the study | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle weakness | The muscle weakness measured weekly by the study team through the Medical Research Council (MRC) | 8 weeks | 
| Ultrasound diaphragm | Weekly the study team will perform diaphragm ultrasound to monitor the respiratory muscles, observing measures of inspiration and expiration. | 8 weeks | 
| ICU length of stay | Patient's length of stay in the intensive care unit after the start of the study as described in the patient record | 9 months | 
| Hospital length of stay | Period of stay of the patient in the hospital after discharge from the intensive care unit described in the patient record | 9 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
anabolic steroid, prolonged mechanical ventilation, critically ill patients