None listed
Conditions
Brief summary
Liver cirrhosis is associated with significant changes in energy metabolism and body composition. Increased resting energy expenditure (REE) is commonly found and is an independent predictor of reduced survival. Short-term intravenous infusion of beta-blockers can reduce REE in cirrhotic patients indicating the potential for long-term beta-blockade to modulate the metabolic and nutritional consequences of cirrhosis. We hypothesised that oral beta-blockade over the longer term will reduce REE. The present randomised, placebo-controlled pilot study aims to determine if 3-month treatment with oral beta-blockers can reduce REE in cirrhotic patients. A positive result from this study would provide a strong rationale for further investigation of their potential for improving survival and reducing the demand for liver transplantation.
Interventions
Randomized, double-blind, crossover trial of nadolol vs placebo; 2 phases of 3 months each with 2-week washout. Nadolol will be commenced at 40mg daily, increasing to 80mg after 1 week. Nadolol and placebo will be dispensed in a form that is indistinguishable. Patients will be re-assessed at 2 weeks after beginning each 3-month phase and, if necessary, the dose of nadolol adjusted to achieve a target resting pulse rate of 60 beats per minute or a 20% reduction in baseline resting pulse rate. Thi
Randomized, double-blind, crossover trial of nadolol vs placebo; 2 phases of 3 months each with 2-week washout. Nadolol will be commenced at 40mg daily, increasing to 80mg after 1 week. Nadolol and placebo will be dispensed in a form that is indistinguishable. Patients will be re-assessed at 2 weeks after beginning each 3-month phase and, if necessary, the dose of nadolol adjusted to achieve a target resting pulse rate of 60 beats per minute or a 20% reduction in baseline resting pulse rate. This adjustment will be made by an unblinded third-party clinician who is not involved with end-point measurements. The patients and investigators will remain blinded to the treatment allocation.
Sponsors
Associate Professor Lindsay Plank
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to -2147483648 No limit
Healthy volunteers
No
Inclusion criteria
Liver cirrhosis, no contra-indications to beta-blockers (history of bronchospasm, severe peripheral vascular disease, complete heart block, previous intolerance to b-blockers, brittle diabetes characterised by recurrent hypoglycaemia), clinically stable and no major complication of liver disease within 1 month of entry, age over 18 years and ability to give informed consent.
Exclusion criteria
Patients requiring primary prophylaxis with beta-blockers, pregnancy, hepatocellular carcinoma, listed for liver transplantation at the time of enrolment.
Outcome results
None listed