EAL

ONC: Branched Chain Amino Acids (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate, in a randomized controlled trial, any benefit of the long-term administration of branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma.

Inclusion Criteria:

Newly diagnosed unresectable HCC
absence of extra-hepatic metastasis
absence of vascular contraindications (hepatic artery thrombosis, main portal vein thrombosis or arteriovenous shunting)
absence of hepatic encephalopathy, ascites refractory to diuretics or variceal bleeding within 3 months
serum bilirubin level of less than 50 umol/L and a serum albumin level above 25 g/L
Karnofsky performance score of 50 or above

Exclusion Criteria:

See above inclusion criteria
Patients with a history of other treatments for the tumor or acute tumor rupture were excluded from the study.

Description of Study Protocol:

Recruitment

Patients were recruited at the University of Hong Kong Medical Center between July 1998 and December 2000 that qualified with the above mentioned inclusion/exclusion criteria.

Design

Patients were randomized into two groups: those that took the BCAA supplement and a control group. Randomization was performed without stratification.

Control group - took their usual diet; no placebo was given secondary to the difficult of matching the taste of the Aminoleban EN.

BCAA group - 50 g Aminoleban EN twice a day in addition to their usual diet. Supplement was started 1 week before the first TACE and continued for up to one year.

No dietary restrictions were imposed unless the patient developed hepatic encephalopathy.

Blinding used (if applicable)

The clinicians assessing the patients in the out-patient clinic were blind to the randomization group of the patients

Intervention (if applicable)

N/A

Statistical Analysis

Continuous variables were expressed as the median (range) and compared using the Mann-Whitney U-test. Categorical variables were compared using the chi-squared test or Fisher's exact test where appropriate. Survival was computed using the Kaplan-Meier method and compared using the log-rank test. A P-value of 0.05 or less by the two-tailed test was considered to indicate statistical significance. All the statistical analyses were performed using statistical software.

Data Collection Summary:

Timing of Measurements

all patients were followed up every fortnight with clinical assessment, complete blood count, liver and renal biochemistry
anthropometric measurements, indocyanine green clearance test and quality of life were evaluated every 3 months before the next TACE session

Dependent Variables

Morbidity
liver function
nutritional status
quality of life
long-term survival

Independent Variables

50 g Aminoleban EN x2/day

Control Variables

Description of Actual Data Sample:

Initial N: 84 (78 males / 6 female)

Attrition (final N): BCAA, 12 pts; Control, 7

Age: BCAA: 59; Control: 59

Ethnicity: unknown

Other relevant demographics: unknown

Anthropometrics: two groups were well balanced with regards to age, sex, presence of comorbid illnesses, liver function, renal function, body weight, tumor characteristics, and Okuda staging.

Location: Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong

Summary of Results:

Findings:

The diets of the two groups were comparable in terms of daily calories and nitrogen intake at all time points.
The baseline liver function parameters were comparable between the two groups
The quality of life score by the FACT-G questionnaire was similar between the two groups before the first TACE. However, a significantly better quality of life as reflected by the scores was observed in the BCAA group.
BCAA group had a significantly lower frequency of ascites (7.3% vs. 23.2%, P=0.043) and peripheral edema (9.8% vs. 27.9%, P=0.034). Ascites and edema were most common causes of morbidity after TACE.
By data analysis, 29 pts in the BCAA group and 36 pts in the control group had died. BCAA group: 22, CA progression; 6, liver failure; 1, unrelated medical condition. Control group: 22, tumor progression; 12, liver failure; 2, unrelated medical condition.
Median hospital stay for both groups for each course of TACE was 2 days
5 patients in the BCAA group and 15 patients in the control group had at least 1 re-admission during the study period for adverse events after TACE. P=0.032

Author Conclusion:

"Nutritional supplementation with oral branched chain amino acids is beneficial in increasing the serum albumin level, reducing the morbidity and improving the quality of life in patients undergoing chemoembolization for inoperable hepatocellular carcinoma."

Funding Source:

University/Hospital:

University of Hong Kong (China)

Reviewer Comments:

The study by Poon et al on nutritional support with branched chain amino acids in HCC patients undergoing non-surgical therapy is a well-designed study in terms of the number of particants, the dependent variables analyzed and the timing of the measurements, as well as the results shown. However, a downfall of this study is the lack of placebo for the control group. This knowledge may have inadvertently changed the quality of food intake with these patients and skewed the results. This study is promising and should be repeated with a larger group for comparison of results.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		???
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		???
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
10.	Is bias due to study's funding or sponsorship unlikely?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	???