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Trial registered on ANZCTR


Trial ID
ACTRN12614000526673
Ethics application status
Approved
Date submitted
31/03/2014
Date registered
19/05/2014
Date last updated
12/01/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Impact of Low Testosterone Levels on Men with Liver Failure, and the Efficacy of Testosterone Therapy
Scientific title
A randomised, double-blinded trial in men with cirrhosis of Testosterone therapy versus placebo to assess the impact on body composition
Secondary ID [1] 284370 0
nil
Universal Trial Number (UTN)
U1111-1155-1323
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cirrhosis 291534 0
Low testosterone 291535 0
Condition category
Condition code
Oral and Gastrointestinal 291913 291913 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 292250 292250 0 0
Normal metabolism and endocrine development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intramuscular Testosterone therapy (Reandron 1000mg) for 12 months, delivered as per manufacturer's instructions at 0, 6, 18, 30, 42 and 54 weeks
Intervention code [1] 289099 0
Treatment: Drugs
Comparator / control treatment
Placebo - an equal volume (4mL) of identically-appearing oil-based solution as provided by Bayer
Control group
Placebo

Outcomes
Primary outcome [1] 291823 0
Muscle mass =appendicular lean muscle mass (kg) as assessed by body composition component of DEXA (dual energy xray absorptiometry) scanning

Timepoint [1] 291823 0
End of trial (12 months)
6 month DEXA also performed and data from patients dropping out between 6 and 12 months will also be analysed
Secondary outcome [1] 307612 0
Bone Mineral Density of the lumbar spine and femoral neck as assessed by DEXA scan
Timepoint [1] 307612 0
12 months
Again, 6 month data will be recorded
Secondary outcome [2] 307613 0
Liver biochemistry: serum assays on routine blood tests
Liver function: albumin, ALT, ALP, GGT, bilirubin, INR
MELD score: creatinine, sodium (and INR)
Timepoint [2] 307613 0
12 months
(data collected 3 monthly)
Secondary outcome [3] 307614 0
Hospital admissions - this will be from a combination of patient interviews and verified by comparing with electronic medical records
Timepoint [3] 307614 0
12 months (recorded 3 monthly)
Secondary outcome [4] 307615 0
Liver transplantation or death - information obtained from medical records
Timepoint [4] 307615 0
12 months
Secondary outcome [5] 307616 0
Metabolic parameters on serum assays
-insulin resistance - estimated by HOMA-IR using serum insulin and serum glucose
-HbA1c
-lipid profile

Total body fat on DEXA scan
-body fat in kg
Timepoint [5] 307616 0
12 months (3 monthly assessment)
Secondary outcome [6] 307617 0
Clinical features: ascites, infection, gynecomastia

-this is obtained from a combination of patient interviews, clinical examination and verification against medical records including medical imaging
Timepoint [6] 307617 0
12 months (3 monthly assessment)
Secondary outcome [7] 307618 0
Quality of Life (QOL): energy levels, mood, physical activity

The questionnaires included ADAM (androgen deficiency in the ageing male), SF36 health outcomes survey, and the IPAQ (international physical activity questionnaire)
Timepoint [7] 307618 0
12 months (assessed 3 monthly)
Secondary outcome [8] 308222 0
Skeletal muscle area on L4 CT scan using tomovision software will also be measured and analysed as a secondary outcome
Timepoint [8] 308222 0
start of trial and end of trial
- all patients will have a CT scan at baseline
- if patients drop out between 6 and 12 months for reasons other than death, they will be asked to have a CT at this time as data will be used
- if patients continue to 12 months their end-of-trial CT will be at 12 months

Eligibility
Key inclusion criteria
Men with cirrhosis with low baseline testosterone levels (<12nmol/L for total testosterone, or <230pmol/L for free testosterone)
Minimum age
18 Years
Maximum age
70 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Cancer - in particular screening must be performed for hepatocellular carcinoma and prostate cancer prior to trial entry

Elevated PSA

Severe renal or cardiac failure

Sleep apnea requiring CPAP

Polycythaemia

Platelets below 30 x 10^6

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 concealment via central randomisation by computer. this was performed by clinical trials pharmacy staff
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation by Pharmacy Clinical Trials staff
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This study was powered to show a 10% difference in appendicular muscle mass on DEXA scan between active and placebo. The dropout rate was estimated to be 30%, and power calculations taking this into account suggested that 88 participants would be required.

We aim to recruit 100 participants to allow for the possibility of a higher dropout rate given an extremely unwell, and often liver transplant waitlisted population

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 2287 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 7966 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 289011 0
Hospital
Name [1] 289011 0
Austin Hospital Medical Research Fund
Address [1] 289011 0
Austin Health
Studley Rd
Heidelberg
Victoria
3084
Country [1] 289011 0
Australia
Funding source category [2] 289012 0
Commercial sector/Industry
Name [2] 289012 0
Bayer Pharmaceuticals
Address [2] 289012 0
Bayer Pharma
AG Muellerstrasse
178 Berlin 13342
Country [2] 289012 0
Germany
Primary sponsor type
University
Name
The University of Melbourne
Address
Austin Hospital Liver Transplant Unit
145 Studley Road
Heidelberg
Victoria
3084
Country
Australia
Secondary sponsor category [1] 287689 0
Hospital
Name [1] 287689 0
Austin Hospital
Address [1] 287689 0
145 Studley Road
Heidelberg
Victoria
3084
Country [1] 287689 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290819 0
Austin Hospital Research Ethics
Ethics committee address [1] 290819 0
145 Studley Rd
Heidelberg
Vic
3084
Ethics committee country [1] 290819 0
Australia
Date submitted for ethics approval [1] 290819 0
Approval date [1] 290819 0
15/01/2013
Ethics approval number [1] 290819 0
H2013/04826

Summary
Brief summary
BRIEF BACKGROUND SUMMARY
1. Low serum testosterone levels are common in men with advanced liver disease
2. Symptoms and signs of testosterone deficiency are common in men with advanced liver disease
3. Low testosterone levels correlate with increased mortality in men with advanced liver disease
HYPOTHESES
1. Testosterone therapy is not associated with significant adverse outcome in men with advanced liver disease
2. Testosterone treatment will increase muscle mass and bone mineral density in men with advanced liver disease
SPECIFIC AIMS
To conduct a single centre randomised controlled trial to assess the efficacy of 12 months of testosterone therapy in men with advanced liver disease and low serum testosterone
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 47402 0
A/Prof Paul Gow
Address 47402 0
Austin Hospital Liver Transplant Unit
145 Studley Rd
Heidelberg
Vic
3084
Country 47402 0
Australia
Phone 47402 0
+613 94965353
Fax 47402 0
Email 47402 0
paul.gow@austin.org.au
Contact person for public queries
Name 47403 0
Dr Marie Sinclair
Address 47403 0
Austin Hospital Liver Transplant Unit
145 Studley Rd
Heidelberg
Vic
3084
Country 47403 0
Australia
Phone 47403 0
+613 94965353
Fax 47403 0
Email 47403 0
marie.sinclair@austin.org.au
Contact person for scientific queries
Name 47404 0
Dr Marie Sinclair
Address 47404 0
Austin Hospital Liver Transplant Unit
145 Studley Rd
Heidelberg
Vic
3084
Country 47404 0
Australia
Phone 47404 0
+613 94965353
Fax 47404 0
Email 47404 0
marie.sinclair@austin.org.au