• Increase Font Size
  • Decrease Font Size
  • View as PDF

ONC: Glutamine (2006)

Citation:

Schloerb, P, Amare, M. Total Parenteral Nutrition With Glutamine in Bone Marrow Transplantation and Other Clinical Applications (A Randomized, Double-Blind Study). Journal of Parenteral and Enteral Nutrition, 1993;17(5):407-413.

PubMed ID: 8289404
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To evaluate the effect of glutamine-supplemented TPN in the BMT population and to evaluate the possible benefits and problems of parenteral L-glutamine.

Inclusion Criteria:
  • All patients who received a bone marrow transplantation (BMT)
  • Signed informed consent

Non-BMT patients- oncology patients

Exclusion Criteria:

None were excluded among patients with BMT.

Non BMT patients: 

  • those with advanced liver or kidney failure
  • and patients with metastatic malignancies who were not receiving chemotherapy or radiation therapy.
Description of Study Protocol:

Recruitment: Patients were recruited from the University of Kansas Medical Center from September 9, 1991 through July 19, 1992. IRB approval was obtained for the study.

Design: Patients were randomized to receive either standard TPN or TPN with L-glutamine.

Blinding used: Patients were randomized using a random number table by a research pharmacist. Double blinding was utilized. There were no attempts made by the researchers to match patients according to diagnosis, sex, cytoreductive treatment, graft vs. host disease, or viral prophylaxis.

The research nurse who recorded the data on patients was not aware of the assignment to the standard TPN or TPN with L-glutamine. At the conclusion of the study, she determined which patients received the standard TPN or TPN with L-glutamine based upon observation of their clinical course and overall well being . She correctly identified 59% of treatments(>.05). With the further subdivision of patients into hematologic  and nonhematologic malignancies,she correctly identified 60% and 58%,respectively(P>.05).

Intervention: Patients were given an isocaloric, isonitrogenous standard TPN or TPN + glutamine (2830 mg/100ml) after BMT until they consumed 50% of their diet orally.

Total body weight,lean body mass and body cell mass (BCM)were calculated ,using a computer program, based upon the patient's age, height and weight. The calories provided were 1.5 times the calculated resting energy expenditure. The protein requirement was 3.2 g/kg BCM; the dextrose requirement was 14 g/kg BCM;and the remaining calories were provided by fat. Parenteral nutrition was discontinued when the patient consumed half of the estimated nutritional requirements on any given day.

Statistical Analysis: Data were analyzed using statical software program (STATA). Chi square test, Student's T-test, and Fisher Exact test were used as appropriate. Any P values below 0.05 were considered significant.

Data Collection Summary:

Timing of Measurements: Total body water and ECW, bioimpedance and bioreactance was measured in 10 patients before BMT and after TPN. No other timing measurements were noted.

Dependent Variables: Patients were followed daily until hospital discharge. Significant clinical events, including drug and blood products given, were recorded. These variable are indicated by an asterisk.

  • Variable 1: Average daily maximal temperature
  • Variable 2: Cumulative mucositis score 
  • Variable 3: Total days on antibiotics
  • Variable 4: Patients receiving amphotericin
  • Variable 5: Patients receiving corticosteriods
  • Variable 6: Blood transfusions
  • Variable 7: Platelet transfusion
  • Variable 8: Days until average neutrophil count >0.5x109/L
  • Variable 9: Patients with no positive cultures*
  • Variable 10: Patients with positive stool cultures (surveillance cultures were obtained).
  • Variable 11: Patients with positive throat cultures (surveillance cultures were obtained).
  • Variable 12: Patients with clinical infections were defined by the presence of positive blood cultures or by signs (temperatures >38.1 degrees C) and symptoms compatible with infection(with or without positive microbial cultures) that prompted the initiation or alteration of antibiotic administration and adjunct care.
  • Variable 13: Change in total body water(L); deuterium dilution and bioimpediance -- total body water (TBW) and extracellular water (ECW)were measured by deuterium oxide-8 and sodium bromide, respectively. These tracers were administered from a weighted syringe containing approximately 10 ml of 12% sodium bromide in 99.8% deuterium oxide. Deuterium oxide was measured with isotope ratio mass spectrometry. Bioimpediance was measured by tracer methods at the times of determination of TBW and ECW.
  • Variable 14: Change in extracellular water (L)
  • Variable 15: Change in weight (Kg)*
  • Variable 16: Length of stay after transplant*
  • Variable 17:Laboratory tests-hemoglobin,hematocrit,white blood cell count,platelet count,serum sodium,potassium,chloride,bicarbonate,albumin,creatinine and blood urea nitrogen concentrations.
  • Independent Variables: Renamin + free l-glutamine (Ajniomoto USA, Teaneck NJ)
  • Control Variables: Travasol

 TPN formulas were discontinued when the patients consumed half of the estimated nutritional requirements on a given day. The nutrient intake of both groups is detailed below.

Patients(n)

 Standard TPN
13		 TPN/GLN
16

Duration of TPN feeding (d)

 31±3 30±5
Intravenous calories (kJ/d)       10,765±368 10,347 ±543

Intravenous nitrogen (g/d)

 16.5±0.7 15.5±0.9

Description of Actual Data Sample:
 

Initial N: 29 (12 females,17 males)

 Patient Characteristics at Study Entry

Standard TPN
(n=13)

TPN/GLN
(n=16)

Sex

Female

Male

 

5

8

 

7

9

Age(y)*  

  35.6

(19-55)    

37.6   

 (19-55)

Weight (kg) * 

    81.6(60.3 to109.5)  

 75.7 (48.4  to  120)             

Ideal Body Weight(%)§

125±31

117±20

BSA(m 2 )*        

 

1.94

(1.59-2.40)

                  

1.86

(1.43-2.37)

Serum albumin(g/L) §

39±5

40±6

Diagnosis(n)

 Acute myeloid leukemia

                  5                

6

Chronic myeloid leukemia

1

4

Hodgkin's lymphoma

2

2

Non-Hodgkin's lymphomia

4

1

Mutiple myeloma

Carcinoma,breast

1

1

Seminoma

0

1

   

                   
Allogeneic transplants

6

7

Autologus transplants                   7        

  9

BSA,body surface area ; *Mean(range);§ Mean ±SEM.     

 

Attrition (final N): 4 patients died, final N=25

non-BMT- 2 patients died, final n=28

Age: 19-55 years. Non-BMT- not specified but 26 adults and 4 pediatrics.

Ethnicity: Not identified

Other relevant demographics: 

15 autologous and 14 allogeneic transplants

Cancer Diagnosis

 Type of Chemotherapy
Allogenic BMT Cyclophosphamide(CY) and total body irradation or CY and busulfan.Total body irradiation was administered as 12 Gy in fractionated doses of 2 Gy twice daily for 3 days.
Autologus BMT of acute leukemia Cyclophosphamide(CY) and total body irradation or CY and busulfan.Total body irradiation was administered as 12 Gy in fractionated doses of 2 Gy twice daily for 3 days.

Lymphoma who underwent autologus BMT

 CY,carcmustine,and etoposide.
Breast carcinoma CY and thiotepa before autologous BMT.
Seminoma CY and thiotepa before autologous BMT.

Medications taken for mucositis: pentoxifylline,nonabsorbable oral antibiotics,including vancomycin,gentamycin,polymyxin,and nystatin.

Anthropometrics: No differences among the subjects were identified.

Location: University of Kansas Medical Center.

Summary of Results:

Variable Standard TPN
(n=13)

TPN/GLN
(n=16)

Statistical Significance of Gropu Difference

Average daily temperature(0C)

38.2±0.1

 38.2±0.1

NS

Cumulative mucositis score

  0.9±0.2

 0.7±0.2

NS

Total days on antibiotics

    18.1±3.1

 15.2±2.7

     NS          

Patients receiving amphotericin B(n)

4

5

NS

Patients receiving corticosteroids(n)

5

       7

NS

Blood transfusions(n)

3±0.8

    4.2 ±1.2         NS

Platelet transfusions(n)

                9±1.5                  

     8.4±3.7

NS

Days until average neutrophil count >0.5x109/L

15±1.9

14±2

NS

Patients with no positive cultures(N) 

2

       5         NS
Patients with positive stool cultures(n) 

7

       10         NS

Patients with positive throat cultures(n)

5

      5

NS

Patients with clinical infections(n)

5

      6                NS
Changes in total body water(L)

 

 

Deuterium dilution

3.1±1.5

 -3.4±1.3

P<.05

Bioimpedance

2.2±0.1

 -1.2±0.8        P< .05

Changes in Extracellular Water(L)

3.2±1.7

 2.0±1.6        NS
Changes in weight(kg)

1.4±0.8

 -0.2±1.0

NS

Length of stay after transplant(d)

32.7±2.1

 26.9±1.3

p<.05

Other Findings: In reporting the results from the non BMT patients ,the authors concluded that the use of glutamine-supplemented TPN appeared to be safe based upon the following factors: 1)the wide variation in diagnoses,2)the few number of patients, and 3)the absence of disease-specific controls prevented evaluation of significant differences in the group. 

Author Conclusion:

1. Length of hospital stay after BMT was significantly(5.8 days) less in patients receiving TPN/GLN.

2. Total body water and extra cellular water increased in patients using the standard TPN formula and decreased in those utilizing the TPN/GLN.

3.The available evidence suggests that enteral feedings,including treatment with L-glutamine, before chemotherapy and irradiation would be more protective. Further study recommended.

Funding Source:
Government: NIH
Industry:
Reviewer Comments:

 This study under review had ethical issues arise which means that it was quasi-experimental in which some aspects of the true experiment had to be modified or dropped. The 12 month  study was dropped at 8 months of research because of the results reported by Zieglar et al(1992) had shown improved nitrogen balance,diminished incidence of clinical infection,lower rates of microbial colonization, and shorten hospital stay compared with patients receiving standard perinatal nutrition. Schloerb and Amare reported  that on ethical grounds , they were not justified in withholding glutamine from their patients after BMT. 

Limitations:

  • funding issues
  • did not include total or average dosing of gln/actual amount taken
  • appears to have used 2 different types of BIA measurement tools
  • BIA data only completed on 10 patients- not sure from which groups
  • did not indicate how oral calories were monitored
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? ???
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.) ???
  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? ???
  4.1. Were follow-up methods described and the same for all groups? ???
  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%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  4.4. Were reasons for withdrawals similar across groups? ???
  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? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  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? N/A
  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? N/A
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? N/A
  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? N/A
  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)? ???
  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? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? ???
10. Is bias due to study's funding or sponsorship unlikely? ???
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? ???