Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000546459
Ethics application status
Approved
Date submitted
19/10/2007
Date registered
23/10/2007
Date last updated
7/11/2018
Date data sharing statement initially provided
7/11/2018
Date results information initially provided
7/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Beta-blockade to reduce energy expenditure in cirrhosis
Scientific title
A randomized pilot study to assess efficacy of beta-blockade for reducing energy expenditure in patients with liver cirrhosis.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver cirrhosis 2475 0
Condition category
Condition code
Other 2576 2576 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 2205 0
Treatment: Drugs
Comparator / control treatment
Placebo (sugar pill).
Control group
Placebo

Outcomes
Primary outcome [1] 3482 0
Change in resting energy expenditure (measured by Deltatrac metabolic monitor)after 3-months treatment (with appropriate adjustment for change in metabolising mass of the body).
Timepoint [1] 3482 0
Beginning and end of each 3-month phase.
Secondary outcome [1] 5812 0
Total body protein (measured by in vivo prompt-gamma neutron activation analysis).
Timepoint [1] 5812 0
Beginning and end of each 3-month phase.
Secondary outcome [2] 5813 0
Quality of life (Short Form 36).
Timepoint [2] 5813 0
Beginning and end of each 3-month phase.
Secondary outcome [3] 5814 0
Skeletal muscle function (grip strength by Lafayette dynamometer and respiratory muscle strengthby Validyne pressure transducer).
Timepoint [3] 5814 0
Beginning and end of each 3-month phase.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients requiring primary prophylaxis with beta-blockers, pregnancy, hepatocellular carcinoma, listed for liver transplantation at the time of enrolment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation by sequentially numbered sealed envelope.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Cumputer-generated randomization sequence.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2007
Actual
1/08/2008
Date of last participant enrolment
Anticipated
Actual
19/08/2009
Date of last data collection
Anticipated
Actual
3/03/2010
Sample size
Target
24
Accrual to date
Final
23
Recruitment outside Australia
Country [1] 628 0
New Zealand
State/province [1] 628 0

Funding & Sponsors
Funding source category [1] 2730 0
University
Name [1] 2730 0
University of Auckland
Country [1] 2730 0
New Zealand
Primary sponsor type
Individual
Name
Associate Professor Lindsay Plank
Address
Department of Surgery
University of Auckland
Private Bag 92019
Auckland
Country
New Zealand
Secondary sponsor category [1] 2466 0
Individual
Name [1] 2466 0
Professor John McCall
Address [1] 2466 0
New Zealand Liver Transplant Unit
Auckland City Hospital
Park Road
Auckland
Country [1] 2466 0
New Zealand
Other collaborator category [1] 80 0
Individual
Name [1] 80 0
Associate Professor Edward Gane
Address [1] 80 0
New Zealand Liver Transplant Unit
Auckland City Hospital
Park Road
Auckland
Country [1] 80 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4644 0
Ethics committee address [1] 4644 0
Ethics committee country [1] 4644 0
Date submitted for ethics approval [1] 4644 0
16/10/2007
Approval date [1] 4644 0
24/01/2008
Ethics approval number [1] 4644 0
Ethics committee name [2] 4645 0
Ethics committee address [2] 4645 0
Ethics committee country [2] 4645 0
Date submitted for ethics approval [2] 4645 0
Approval date [2] 4645 0
Ethics approval number [2] 4645 0

Summary
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.
Trial website
Trial related presentations / publications
Lee WG, McCall JL, Gane EJ, Murphy R, Plank LD. Oral ß-blockade in relation to energy expenditure in clinically stable patients with liver cirrhosis: a double-blind randomized cross-over trial. Metabolism 2012; 61; 1547-1553. doi:10.1016/j.metabol.2012.04.001.
Public notes

Contacts
Principal investigator
Name 28127 0
Address 28127 0
Country 28127 0
Phone 28127 0
Fax 28127 0
Email 28127 0
Contact person for public queries
Name 11284 0
Associate Professor Lindsay Plank
Address 11284 0
Department of Surgery
University of Auckland
Private Bag 92019
Auckland
Country 11284 0
New Zealand
Phone 11284 0
+64 9 3074935
Fax 11284 0
+64 9 3779656
Email 11284 0
[email protected]
Contact person for scientific queries
Name 2212 0
Associate Professor Lindsay Plank
Address 2212 0
Department of Surgery
University of Auckland
Private Bag 92019
Auckland
Country 2212 0
New Zealand
Phone 2212 0
+64 9 3074935
Fax 2212 0
+64 9 3779656
Email 2212 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.