Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610001021066
Ethics application status
Approved
Date submitted
5/11/2010
Date registered
22/11/2010
Date last updated
11/02/2021
Date data sharing statement initially provided
11/02/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Effects of Synbiotics, Branched Chain Amino Acids on Hepatic Encephalopathy
Scientific title
The effects of supplementation with synbiotics, branched chain amino acids on levels of hepatic encephalopathy in patients with cirrhosis
Secondary ID [1] 253127 0
2010/0046
Universal Trial Number (UTN)
U1111-1117-7730
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatic encephalopathy in patients with cirrhosis 258592 0
Condition category
Condition code
Oral and Gastrointestinal 258732 258732 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Diet and Nutrition 258733 258733 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. Synbiotics + branched chain amino acids (BCAAs)
2. BCAAs + Placebo for Synbiotics
3. Placebo for BCAAs + Placebo for Synbiotics

1. Synbiotic 2000 Forte is packaged in 10g single dose sachets which contain: Natural and digestible fibres: * 2.5g oat bran; * 2.5g pectin; * 2.5g resistant starch; * 2.5g inulin. Probiotic bacteria: * Lactobacillus paracasei ssp paracasei 10 x 10¹¹; * Lactobacillus plantarum 10 x 10¹¹; * Leuconostoc mesenteroides 10 x 10¹¹; * Pediococcus pentosaceus10 x 10¹¹ (Medipharm). Dose is 1 sachet/day mixed with juice, jam or honey according to patient's tolerance. Duration of supplementation is 56 days.
2. Branched Chain Amino Acid preparation - Hepatamine (Nutricia) which is a mixture of branched chain amino acids + sugars. Dose is 1 sachet at night mixed with 200ml lemonade, fruit juice. Duration of supplementation is 56 days."
Intervention code [1] 257561 0
Treatment: Other
Comparator / control treatment
1. Placebo for Synbiotics is 10g crystalline starch packaged similarly to Synbiotic Forte
Dose is 1 sachet/day mixed with juice, jam or honey according to patient's tolerance
Duration of supplementation is 56 days


2. Placebo for BCAAs is 29g glucose + 15 g Vitafresh
Dose is 1 sachet at night mixed with 200ml lemonade, fruit juice
Duration of supplementation is 56 days
Control group
Placebo

Outcomes
Primary outcome [1] 259600 0
Effects of supplementation with Synbiotics and/or branched chain amino acids (BCAAs) on levels of hepatic encephalopathy
This is assessed using the Trail Making Tests A and B and the Inhibitory Control Test.
In addition, biochemical markers for liver function and inflammatory processes as well as changes in quality of life and nutritional responses to interventions will also be collated (CTP, MELD, TNF, IL-6, MAC, TSF, MAMC, food intakes, hospitalisations, depression and anxiety scores and LDSFQOL
Timepoint [1] 259600 0
Timepoints at baseline, one month and 2 months after randomisation
Secondary outcome [1] 266233 0
Effects of Synbiotics and/or BCAAs on rates of infection - subacute bacterial peritonitis (SBP) in particular - this will be assessed by recording hospitalisations secondary to episodes of SBP Diagnosis of SBP will be made at culture and cell count analysis of ascitic fluid obtained routinely or in the presence of symptoms, and in the absence of surgically treatable intra-abdominal source of infection
Timepoint [1] 266233 0
Timepoints at baseline, one month and 2 months after randomisation
Secondary outcome [2] 266234 0
Effects of Synbiotics and/or BCAAs on proinflammatory cytokines TNF and IL-6

5mls whole blood will be spun down and approx 2ml serum will be labelled and stored at -80 degrees celsius

Aliquots of serum will be assayed for serum TNF and IL-6 using a commercial enzyme-linked immunosorbent assay (ELISA) in a 96 well plate format according to instructions
Timepoint [2] 266234 0
Timepoints at baseline, one month and 2 months after randomisation
Secondary outcome [3] 266235 0
Effects of Synbiotics and/or BCAAs onquality of life outcomes measured by liver disease short form quality of life (SFLDQOL) questionnaire and depression and anxiety score (DASS)
Timepoint [3] 266235 0
Timepoints at baseline, one month and 2 months after randomisation
Secondary outcome [4] 266238 0
Effects of supplementation with Synbiotics and/or BCAAs on frequency of hospitalisation
Patients are reviewed prior to entry into the study and at 1 month after entry and at 2 months on completion of the study. The number of hospitalisations each month, the cause (s)of admission(s) and duration of admission (s) are documented at each time point
Timepoint [4] 266238 0
Timepoints at baseline, one month and 2 months after randomisation
Secondary outcome [5] 266239 0
Effects of supplementation with Synbiotics and/or BCAAs on the severity of the patient's chronic liver disease using the Childs Pugh Score (CTP) and Model for End Stage Liver Disease (MELD)
Timepoint [5] 266239 0
Timepoints at baseline, one month and 2 months after randomisation
Secondary outcome [6] 266240 0
Effects of supplementation with Synbiotics and/or BCAAs on body composition and hand grip strength
Body composition is assessed by anthropometry - measurements of midarm circumference and triceps skinfold and calculated midarm muscle circumference
Handgrip strength is measured using a dynamometer
Timepoint [6] 266240 0
Timepoints at baseline, one month and 2 months after randomisation
Secondary outcome [7] 266241 0
Effects of supplementation with Synbiotics and/or BCAAs on appetite and oral intake
Appetite is a subjective assessment by the patient using a visual analogue scale
Oral intake is assessed using a 3 day food history recorded by the patient at each time point
Timepoint [7] 266241 0
Timepoints at baseline, one month and 2 months after randomisation

Eligibility
Key inclusion criteria
Childs B or C cirrhosis on lactulose aged between 18 - 70 yrs who are abstinent from alcohol and illegal drugs for at least six months. If on methadone must be dose stable for >6 months
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
pregnancy
< 18yrs
> 70yrs
current alcohol use
current iv drug use
sepsis
grade 4 encephalopathy

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 to intervention is randomised by sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients are randomised on enrollment into the study. They select their study code number(in a sealed envelope) from a bag. The code number corresponds to a particular supplement combination. The observer is blinded to the codes.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Randomised into 4 separate intervention arms
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/04/2010
Actual
30/03/2010
Date of last participant enrolment
Anticipated
Actual
2/06/2014
Date of last data collection
Anticipated
Actual
30/07/2014
Sample size
Target
80
Accrual to date
Final
62
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 258011 0
Self funded/Unfunded
Name [1] 258011 0
Country [1] 258011 0
Australia
Primary sponsor type
Hospital
Name
Royal Prince Alfred Hospital
Address
Missenden Road
Camperdown
NSW 2050
Country
Australia
Secondary sponsor category [1] 257204 0
Hospital
Name [1] 257204 0
Liverpool Hospital
Address [1] 257204 0
Locked Bag 7103
Liverpool BC NSW 1871
Country [1] 257204 0
Australia
Secondary sponsor category [2] 257206 0
None
Name [2] 257206 0
Address [2] 257206 0
Country [2] 257206 0
Other collaborator category [1] 251643 0
Individual
Name [1] 251643 0
Dr Nicholas Shackel
Address [1] 251643 0
AW Morrow Gastroenterology and Liver Centre
Royal Prince Alfred Hospital
Camperdown
NSW 2050
Country [1] 251643 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260005 0
Sydney Local Health District (RPAH Zone)
Ethics committee address [1] 260005 0
Ethics committee country [1] 260005 0
Australia
Date submitted for ethics approval [1] 260005 0
14/08/2013
Approval date [1] 260005 0
14/08/2013
Ethics approval number [1] 260005 0
HREC/09/RPAH/5

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31877 0
A/Prof Nicholas Shackel
Address 31877 0
A W Morrow Gastroenterology and Liver Centre
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 31877 0
Australia
Phone 31877 0
+61 434 603 129
Fax 31877 0
Email 31877 0
[email protected]
Contact person for public queries
Name 15124 0
Helen Vidot
Address 15124 0
Department Nutrition and Dietetics
RPAH
Missenden Road
Camperdown
NSW 2050
Country 15124 0
Australia
Phone 15124 0
+ 61 2 9515 8053
Fax 15124 0
+61 2 9515 5047
Email 15124 0
[email protected]
Contact person for scientific queries
Name 6052 0
Dr Nicholas Shackel
Address 6052 0
A W Morrow Gastroenterology and Liver Centre
RPAH Missenden Rd
Camperdown
NSW 2050
Country 6052 0
Australia
Phone 6052 0
+61 434 603 129
Fax 6052 0
+61 2 9515 5047
Email 6052 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
SourceTitleYear of PublicationDOI
EmbaseProbiotics for people with hepatic encephalopathy.2017https://dx.doi.org/10.1002/14651858.CD008716.pub3
N.B. These documents automatically identified may not have been verified by the study sponsor.