EAL

ONC: Glutamine (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

This study sought to assess the influence of supplementation of a stable glutamine-dipeptide on the severity of neutropenia and extra medullary chemotherapy toxicity.

Inclusion Criteria:

Not very specific, but included:

Patients receiving intensive chemotherapy with an expected neutropenic period of 3 weeks.
Informed consent.

Exclusion Criteria:

Two patients died during the study and were excluded from statistical calculations.

Description of Study Protocol:

Recruitment: Patients receiving intensive chemotherapy with an expected neutropenic period of approximately 3 weeks. The patients were randomized at each treatment cycle and not per individual. In each group, 10 treatment cycles were studied. Two patients underwent 3 treatment cycles and were randomized 3 times; one patient was randomized twice and the other patients once. 15 patients with 20 treatment cycles were studied.

Design: A prospective double blind study comparing conventional TPN with an isonitrogenous and isoenergetic TPN containing Ala-Gln.

Blinding used: Patients were randomized on the decision of the pharmacist by balanced assignment to receive either standard TPN or TPN with Ala-Gln.

Intervention: TPN was supplied as "all in one". The amino acid content of of the standard solution was uniformly reduced to accomodate 40g. alanyl-glutamine corresponding to 26g free glutamine. The solutions were isonitrogenous (0.272 g nitrogen/kg body weight) and isocaloric (2200 kcal nonprotein energy/day), containing equal amounts of ascorbic acid, soluvit N, vitalipid, and trace elements. TPN was started concomitantly with the chemotherapy or 1 day after the bone marrow transplantation. The therapy was discontinued when the neutrophil count reached 0.5 x 109/l.

Statistical Analysis: Differences between the two groups were compared with the Mann-Whitney U test. A P value of 0.05 or less was considered to indicate statistical significance.

Data Collection Summary:

Timing of Measurements: Glutamine and glutamine concentrations in plasma were determined 3 times a week after an overnight fast.

Dependent Variables

Mean oral food intake
Duration of TPN (days)
Weight status
Length of hospital stay (days)
Mucositis
Diarrhea
Duration of neutropenia (days)

Independent Variables: Standard TPN or TPN with 40 g. alanyl-glutamine.

Control Variables: Intensive chemotherapy

Description of Actual Data Sample:

Initial N: 20 (10 Standard TPN / 6 females, 4 males; 10 TPN + Glutamine / 2 females, 8 males)

Final N: 18 ( 8 Standard TPN, 10 TPN + Glutamine)

Mean Age (Range): 49.2 years (32-72) Standard TPN; 49.2 years (20-77) TPN + Glutamine

Anthropometrics:

Mean Body weight (range): 75.2 kg (58-88) Standard TPN; 73.1 kg (50-87) TPN + Glutamine
Mean % IBW (range): 109%IBW (90-128%) Standard TPN; 101%IBW (79-113) TPN + Glutamine
Mean Serum Albumin before treatment (range): 44 g/L (33-50) Standard TPN; 43 g/L (37-49) TPN + Glutamine

Summary of Results:

Variables

Standard TPN

Measures and confidence intervals

TPN + glutamine

Measures and confidence intervals

Statistical Significance of Group Difference

Mean oral food intake

protein (g/day)

estimated glutamine (g/day)

energy(kJ/day)

duration of TPN (days)

gain in weight (kg) per treatment cycle

Glutamine + glutamine levels (Mmol/L)

length of hospital stay

Mean

3064

1.3

534

Mean

41.5

3.3

4898

4.4

718

0.05

Mucositis *

Diarrhea *

Duration of neutropenia days

0.3

0.1

18.5

*Toxicity grade according to WHO classification (scale 0-4)

Other Findings: No side effects or allergic reactions were noted after the dipeptide administration.

Author Conclusion:

The results of this study revealed no significant differences between the standard and glutamine supplemented TPN in cytopenia, microbiologic parameters, or toxicity scores of patients undergoing intensive chemotherapy.
The only significant difference observed between the standanrd and glutamine supplemented TPN was a gain in body weight per treatment cycle.
The patients in the glutamine group had a higher mean oral food intake, but this could not totally explain the difference in gain in body weight.
The poor efficiency of high amounts of dipeptides in these critically ill patients, as seen in the results obtained in the current study, may raise the question of whether the ability to use glutamine as a nutritional substrate is seriously limited during severe stress.

Funding Source:

Industry:

Fresenius AG

Other:

University/Hospital:

University of Hohenheim (Germany)

In-Kind support reported by Industry:

Yes

Reviewer Comments:

The sample size was small, fifteen patients with 20 treatment cycles were studied.

Inclusion and exclusion criteria not extremely specific although enough relevance for this particular study group.

Overall, good study with adequate treatment cycles and statistical analysis.

Agree with the authors that this study showed no benefit in supplementing with glutamine on mucositis and diarrhea in hematologic patients receiving intensive chemotherapy except for a gain in body weight.

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?	No
	2.2.	Were criteria applied equally to all study groups?	???
	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?		No
	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?	No
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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?	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	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?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	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)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	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?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	N/A
	10.2.	Was the study free from apparent conflict of interest?	Yes