None listed
Conditions
Brief summary
Many cirrhotic men have reduced testosterone (T) levels. We recently found that testosterone deficiency is an independent predictor of death in this population. One possible explanation for this is that testosterone deficiency contributes to sarcopenia, a known risk factor for the development of both serious infections and mortality in cirrhotics. In a recent 12 month randomised study we showed that testosterone treatment has multiple short term beneficial effects in testosterone deficient cirrhotic men. These included improvement of sarcopenia, increased bone mass and increased haematocrit. However, this study was not powered to assess the effects of testosterone treatment on the major clinical endpoints linked to sarcopenia in cirrhosis of infection and death. We therefore propose to conduct a multi-centre randomised placebo-controlled trial (RCT) of 24 months T treatment in 250 cirrhotic men with a low T level (serum total T < 12nmol/L or free T < 230pmol/L) to investigate whether T treatment will reduce the composite outcome of mortality or hospitalisation for infection. Primary hypothesis: In cirrhotic men with low testosterone, T therapy will reduce the composite outcome of mortality or hospitalisation for infection, a major trigger for decompensation in chronic liver disease Secondary hypotheses: T treatment will improve the following measures: total numbers of days in hospital, muscle mass, muscle function, bone mass, fat mass, insulin resistance, haemoglobin and quality of life Aim: To conduct a 2-year, multi-centre, randomised, double-blinded, placebo-controlled trial to determine if T treatment together with dietary and exercise advice improves outcomes in men with cirrhosis.
Interventions
Intramuscular testosterone undecanoate (1000mg in 4mL) administered according to manufacturer instructions (0 weeks, 6 weeks, then 12 weekly thereafter) for 24 months
All doses will be administered on-site by nursing staff and logged by trial staff
Sponsors
Austin Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
Male
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Men with cirrhosis and low serum testosterone -cirrhosis defined on clinical grounds, by a combination of clinical, biochemical and radiological features. In equivocal cases, a fibroscan reading of >20kPa is required to avoid the inadvertent inclusion of non-cirrhotics -low serum testosterone requires 2 x morning blood samples that meet criteria: total T <12nmol/L OR free T <230pmol/L
Exclusion criteria
1) Prostate cancer, elevated PSA or abnormal prostate on digital rectal exam 2) Hepatocellular or other active cancer 3) Current or previous (within 12 months) testosterone or androgen deprivation therapy 4) Severe renal impairment (eGFR <30ml/min) 5) Symptomatic ischaemia heart disease or significant heart failure symptoms (New York Heart Association class III or IV) 6) Uncontrolled hypertension >160/100mHg 7) Uncontrolled obstructive sleep apnoea 8) Platelet count <30 x 10^9 given the need for intramuscular drug administration 9) Other non-liver disease thought to lead to death or severe debility within 2 years
Outcome results
None listed