ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12618000802202

Ethics application status

Approved

Date submitted

3/05/2018

Date registered

11/05/2018

Date last updated

12/07/2023

Date data sharing statement initially provided

2/05/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

The Impact of Branched Chain Amino Acids (BCAA) Supplementation in Patients with Advanced Liver Disease

Scientific title

The impact of Branched-Chain Amino Acid supplementation on sarcopenia, insulin resistance and immune function in patients with advanced liver disease

Secondary ID [1]

-Nil known

Universal Trial Number (UTN)

U1111-1213-3605

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Cirrhosis

Sarcopenia

Malnutrition

Hepatic encephalopathy

Infections

Insulin resistance

Immune function

Condition category

Condition code

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Diet and Nutrition

Other diet and nutrition disorders

Infection

Studies of infection and infectious agents

Inflammatory and Immune System

Other inflammatory or immune system disorders

Metabolic and Endocrine

Diabetes

Musculoskeletal

Other muscular and skeletal disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Patients with cirrhosis, muscle weakness as defined by handgrip dynamometer and evidence of low serum albumin or ascites will be invited to participate in the study. 150 patients will be recruited and randomised to the intervention arm and a control arm. The intervention arm will be blinded to receive powdered BCAA supplements. These contain leucine, isoleucine and valine in a 2:1:1 ratio respectively. Patients in the intervention arm will be given powdered BCAA supplements and will be asked to take 30g orally per day mixed with water, milk or juice. The duration of intervention will be 12 months. Compliance will be monitored through return and weighing of supplement packages at each clinical review.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Patients randomised to the control arm will be given a whey protein isolate powder with equal protein content to BCAA supplement. They will be asked to take 30g orally per day for 12 months.

Control group

Active

Outcomes

Primary outcome [1]

Upper limb muscle mass as measured by Dual energy X-ray Absorptiometry (DEXA)

Timepoint [1]

Upper limb muscle mass will be assessed at baseline, 6 months and 12 months [primary timepoint] of intervention.

Primary outcome [2]

Changes in handgrip strength as measured by handgrip dynamometry

Timepoint [2]

Handgrip strength will be assessed at baseline, 1 month, 3 months, 6 months, 9 months and 12 months [primary timepoint] of intervention.

Secondary outcome [1]

Changes in muscle mass as defined by an increase in skeletal muscle index calculated via on single Slice CT scan at 3rd Lumbar vertebrae

Timepoint [1]

Assessment at baseline and 12 months of treatment

Secondary outcome [2]

Changes in functional measures of sarcopenia including Fried Frailty Index and Short Physical Performance Battery

Timepoint [2]

Assessed at baseline, 3, 6, 9 and 12 months of treatment

Secondary outcome [3]

Change in serum biochemistry (liver function tests, albumin)

Timepoint [3]

Measures to be taken at 0, 1, 3, 6, 9 and 12 months of intervention

Secondary outcome [4]

Insulin resistance as measured by HbA1C, HOMA-IR and HOMA-%B scores calculated using fasting insulin and glucose recordings.

Timepoint [4]

Assessed at 0, 1, 3, 6 and 12 months of treatment

Secondary outcome [5]

Immune function as measured by QUANTIFERON-Monitor assay

Timepoint [5]

Assessed at 0, 1, 3, 6, 9 and 12 months of treatment

Secondary outcome [6]

Quality of life measures as assess using the chronic liver disease questionnaire (CLDQ)

Timepoint [6]

Assessed at 0, 3, 6, 9 and 12 months of treatment

Secondary outcome [7]

Anthropometry: triceps skinfold measured by skinfold calipers, and mid-upper arm circumference measured with tape measure

Timepoint [7]

Measured at baseline, 3 months, 6 months, 9 months and 12 months of treatment

Secondary outcome [8]

Rates of hepatic encephalopathy measured using the trail making test and Stroop Test

Timepoint [8]

Measured at 0, 3, 6 and 12 months of treatment

Secondary outcome [9]

Rates of hospitalisation
Outcome measured via data linkage to medical records.

Timepoint [9]

As measured in days over 12 months of intervention

Secondary outcome [10]

Rates of clinical significant infections.
Outcome measured via data linkage to medical records.

Timepoint [10]

Measured in episodes over 12 months of intervention.

Secondary outcome [11]

Direct healthcare costs
Outcome measured by admissions to hospital via data linkage to medical records

Timepoint [11]

Measured at 12 months of intervention

Secondary outcome [12]

Changes in fat mass as measured by single slice CT scan and DEXA body composition

Timepoint [12]

Measured at 0m and 12m post intervention commencement.

Secondary outcome [13]

Liver Frailty Index

Timepoint [13]

0, 3, 6, 12 months post intervention commencement

Eligibility

Key inclusion criteria

Adult patients who meet the following criteria will be invited to participate
1. Cirrhosis with a radiological, clinical or histological diagnosis
2. A low serum albumin or the presence of ascites
3. Muscle weakness as determined by hand dynamometer

Minimum age

18 Years

Maximum age

75 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

- Patients > 75 and < 18 years of age
- Prognosis or time to transplant < 6 months as determined by the treating clinician
- Active heavy alcohol intake
- Advanced hepatocellular carcinoma
- Lactose intolerance

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)

Randomisation will occur independently through the pharmacy department. Patients will be administered the intervention or standard of care supplement powder in unlabelled packaging. The investigator and participant will be blinded to intervention group.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Simple randomisation using a randomisation table created by computer software

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 2

Type of endpoint/s

Statistical methods / analysis

To detect a difference at 12 months between the intervention and control group using the composite endpoints of a difference of 5% in upper limb appendicular muscle mass on DEXA and / or 5% increase in handgrip strenght, with a p-value set at 0.05 and a power of 80%, we estimate that each group will need 67 subjects. We estimate a drop-out rate of up to 10%, therefore we aim to recruit 150 patients.

Outcomes will be analysed on an intention to treat analysis. While most subjects will reach at least 6 months in the study some may drop because of transplantation or death. Those who achieve between 6 and 12 months follow up will be included in the intention to treat analysis provided a DEXA is completed allowing for documentation of APLM. If anything, this will skew results to the null hypothesis as less of a change in APLM is expected at only 6 months follow up compared to the intended duration of 12 months. Therefore, if anything, dropouts may lead to an under-estimation of treatment effect and minimize the risk of identifying a false positive result.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

4/06/2018

Actual

25/07/2018

Date of last participant enrolment

Anticipated

1/04/2021

Actual

1/06/2021

Date of last data collection

Anticipated

1/06/2022

Actual

7/06/2022

Sample size

Target

150

Accrual to date

Final

150

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment postcode(s) [1]

3084 - Heidelberg

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Austin Medical Research Foundation

Address [1]

145 Studley Rd,
Heidelberg, VIC, 3084

Country [1]

Australia

Primary sponsor type

Hospital

Name

Austin Health

Address

145 Studley Rd,
Heidelberg, VIC, 3084

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Human Research Ethics Committee

Ethics committee address [1]

145 Studley Road
Heidelberg VIC 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

22/11/2017

Approval date [1]

14/05/2018

Ethics approval number [1]

Summary

Brief summary

Advanced liver disease, or cirrhosis, is associated with increased morbidity and mortality and patients suffer frequent complications. Sarcopenia, defined as the the loss of muscle mass as well as muscle function, is among the commonest complications, with an estimated prevalence of up to 70%. Sarcopenia is independently associated with reduced survival, increased infection risk and higher rates of hospitalisation in this cohort. Despite this, little is known about how to increase muscle mass in this population.  

Branched chain amino acids (BCAAs) include three essential amino acids which are used as building blocks for protein and energy in muscle. In addition to being the primary energy source for skeletal muscle, they are also used to help clear toxins that build up in liver disease. Patients with cirrhosis have reduced levels of BCAAs, which is thought to be a major contributing factor that contributes to low muscle mass in these patients. 

Treating patients with oral BCAA supplements, in the form of a soluble powder, may improve quality of life and overall nutrition in patients with cirrhosis. However, the impact on muscle mass is unknown. Our study aims to investigate the effect of oral BCAA powdered supplements on sarcopenia in patients with cirrhosis. Our randomised trial will compare BCAAs to a control protein supplement to assess whether replacing dietary protein deficit as a whole or BCAAs specifically can influence outcomes. Our primary outcome will be an increase in muscle mass and strength in treated subjects. If we can improve sarcopenia, we anticipate we may also improve other outcomes. Therefore, our secondary outcomes of this study will be improved muscle function, hepatic encephalopathy, insulin resistance, rates of hospitalisation, health care costs, quality of life and overall mortality. Given the higher rates of infections seen in patients with sarcopenia, the second focus of our study will be on immune function through monitoring blood samples and infectious complications.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Paul Gow

Address

Austin Health
145 Studley Rd
Heidelberg, VIC, 3084

Country

Australia

Phone

+61 3 9496 5353

Fax

paul.gow@austin.org.au

Contact person for public queries

Name

Penelope Hey

Address

Austin Health
145 Studley Rd
Heidelberg, VIC, 3084

Country

Australia

Phone

+61 3 9496 5353

Fax

penelope.hey@austin.org.au

Contact person for scientific queries

Name

Penelope Hey

Address

Austin Health
145 Studley Rd
Heidelberg, VIC, 3084

Country

Australia

Phone

+61 3 9496 5353

Fax

penelope.hey@austin.org.au

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

Source	Title	Year of Publication	DOI
Embase	Moving computed tomography-based quantification of muscle mass to the mainstream: Validation of a web-based platform to calculate skeletal muscle index in cirrhosis.	2022	https://dx.doi.org/10.1002/lt.26538

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically