Oral Supplementation of Glutamine on Gastric Cancer Patients After Gastrectomy
Phase: NA
Conditions: Gastric Cancer, Immunonutrition, Gastrostomy
Sponsor: National Taiwan University Hospital

1    Study Title: Oral Supplementation of Glutamine on Gastric Cancer Patients After 
Gastrectomy              Version date:  2022/11/03 
Study Protocol with SAP 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Title: Oral Supplementation 
of Glutamine on Gastric Cancer 
Patients After Gastrectomy 
 
Date of the document: 11-03-2022 
 
 
 

2    Study Title: Oral Supplementation of Glutamine on Gastric Cancer Patients After 
Gastrectomy              Version date:  2022/11/03 
Specific aims 
Glutamine has the potentials of immunomodulation and adjustment of protein metabolism. 
The primary objective of this study is to evaluate the efficacy of glutamine on sarcopenia in 
gastric adenocarcinoma patients undergoing gastrectomy. The secondary endpoints, including 
the physical activity, weight loss, and nutritional profiles, will be evaluated among these 
patients. 
 
Background and significance 
Gastric adenocarcinoma (GA) is one of the most common foregut cancers worldwide and is 
often diagnosed at advanced stages unless routine endoscopy is done.1 Dysphagia and loss of 
body weight are often encountered in GA patients with advanced stages of cancer. Radical 
gastrectomy plus lymphadenectomy is considered as the only potentially curative treatment. 
However, it is accompanied by a high rate of morbidity and mortality, especially in the GA 
patients with major comorbidities, poor physical activity, or malnutrition.2-4 Notably, in the 
postoperative period, GA patients suffer from the deterioration of strength in skeletal muscles 
and poor quality of life due to the complex reconstruction of the gastrointestinal tract and 
gastrointestinal tract sequelae.5 Since physical activity is associated with outcomes in GA 
cases, its improvement is crucial. 
Sarcopenia, previously known as muscle weakness 6 or cancer-related cachexia 7, is measured 
as the skeletal muscle index (SMI), ≤55 cm2/m2 for men and ≤39 cm2/m2 for women.8 SMI is 
strongly correlated with the cross-sectional area of psoas major muscle (PMMA) at the third 
lumbar vertebra (L3), which provides an easier method to assess the severity of sarcopenia 
among GA patients.9 This parameter is often measured using abdominal computed 
tomography (CT). Recently, there are increasing studies investigating the association between 
sarcopenia and outcomes, and this correlation is highlighted in surgical patients for foregut 
cancer.6,10 

3    Study Title: Oral Supplementation of Glutamine on Gastric Cancer Patients After 
Gastrectomy              Version date:  2022/11/03 
Moreover, physical activity (PA) is a well-known parameter to both assess the general 
condition and monitor the recovery of patients. 11,12 Among the patients undergoing major 
surgery, the physical activity also deteriorated because of the surgical stress and insults, which 
caused afterward decreased quality of life and poor outcomes.13,14 Although the double-
labeled water method is recognized as the gold standard for assessing total energy 
expenditure, it is rarely implemented in clinical practive due to expensive costs and 
complicated process. 15,16 As a result, other modalities, such as self-report questionnaires, self-
report activity diaries, direct observation, and smart watch, have been developed to replace 
the DLW method. 16 
Glutamine is the most abundant non-essential amino acid in humans; it is depleted under 
hypermetabolic and hyper catabolic conditions, such as severe illness or major surgery.17,18 
Since glutamine is involved in diverse processes, including protein metabolism19 and immune 
system modulation20, its insufficiency results in negative nitrogen balance causing significant 
dysfunction of the gut barrier and wound healing.21 Several studies support that glutamine 
supplementation is beneficial for the recovery of patients from critical illness as well as 
chemotherapy-related side effects.22-24 However, the impact of glutamine supplementation on 
sarcopenia was inconclusive.25 
Therefore, this study was conducted to evaluate whether postoperative oral use of glutamine 
aids in improving sarcopenia and physical activity in GA patients undergoing gastrectomy. We 
hypothesized that glutamine might play a role in improving sarcopenia and physical activity. 
As CT is routinely performed in surgical GA patients to check for cancer recurrence, we used 

4    Study Title: Oral Supplementation of Glutamine on Gastric Cancer Patients After 
Gastrectomy              Version date:  2022/11/03 
PMMA to assess the severity of sarcopenia. The primary endpoint was the perioperative 
change in PMMA. Further, the physical activity is defined as the daily walking steps recorded 
by one smart watch. The secondary end-points are the change of walking steps between the 
data from the preoperative period and three months post gastrectomy, weight loss, and 
nutritional profiles. A linear regression model was used to predict this association. 
 
Experimental design and methods 
 
Protocol Synopsis 
Test immunomodulating formula:  
1. Name: Glutamine 
2. Dosage Form: Dry powder  
  3. Dose(s): 10 g glutamine + 5 g Maltodextrin /pack 
  4. Dosing Schedule:  
(1) Control Group:  
15 g Maltodextrin for 28 days after surgery with tolerable oral intake or enteral feeding 
(2) Treatment Group:  
10 g glutamine +5 g Maltodextrin for 28 days after surgery with tolerable oral intake or 
enteral feeding 
 
Study Design: 
1. □v Control: 
 □v placebo   
□active 
 (please specify name and dosage)            
□other     
□Uncontrolled  
2. Blinding: □open-label   □evaluator blind  □single blind   □v double blind  
□double dummy   □other              
3. Randomized:  □v yes    □no  
4. □v Parallel   □Cross-over   □Other           
5. Duration of treatment:  28   days      weeks     months      years 
6. Titration: □forced    □optional   □v none  

5    Study Title: Oral Supplementation of Glutamine on Gastric Cancer Patients After 
Gastrectomy              Version date:  2022/11/03 
7. □Multi-national  □Multi-center (in Taiwan)  □v Single center    
Endpoints 
1. Primary Endpoint: 
Change of area of psoas muscle  
2. Secondary Endpoint: 
(1) Walking steps 
(2) Weight loss 
(3) Change of serum albumin value, pre-albumin value, white blood counts, and lymphocyte 
counts  
 
Selection Criteria: 
1. Inclusion Criteria: 
1. gastric cancer patients undergoing gastric surgery 
2. age ≧20 years old 
2. Exclusion Criteria: 
• 
Hepatic insufficiency 
• 
Renal insufficiency 
• 
can not tolerate oral or enteral feeding 7 days after gastrectomy 
• 
can not receive computed tomograph 
• 
can not waer the wearable devices 
 
 Study Procedures: 
This will be a double-blind, randomized, and placebo-controlled study. At least 80 evaluable 
patients who are scheduled for gastrectomy for gastric adenocarcinoma cancer will be randomly 
assigned to the control or treatment group. Each group will have at least 40 patients. The CT 
scan will be evaluated before surgery and on POD 90. Moreover, the patient will wear the smart 
watch to record daily walking steps. Laboratory data will be check before gastrectomy and on 
POD 90. 
The detailed clinical schedule is as shown in Appendix I. 

6    Study Title: Oral Supplementation of Glutamine on Gastric Cancer Patients After 
Gastrectomy              Version date:  2022/11/03 
Statistics: 
1. Primary hypothesis: 
□v superiority    □non-inferiority 
 
 
 
 
 
    □equivalence   □other          
 
2. Sample size:  Enrolled    100 (estimated)  
               Evaluable    at least 80    
⚫ 
Given a one-sided α level of 2⋅5 percent and assuming a treatment response  rate of 92 
percent for glutamine and to have 80 per cent power to test this RCT. The final planned 
sample size was 100 patients. 
⚫ 
After enrolment, patients were randomized in a 1 : 1 ratio, using opaque, sealed, 
sequentially numbered envelopes containing computer-generated allocation numbers. 
 
3. Efficacy population: □v ITT   □v PP   □other              
 
4. Statistical method(s) for efficacy/safety evaluations: 
To compare differences in terms of the efficacy parameters, between the study groups, 
parametric or non-parametric approaches will be applied as appropriate, mainly, paired t-test, 
two-sample t test, Wilcoxon two-sample test, or chi-square test (or the Fisher’s exact test). 
Linear regression models will be developed to validate the association between outcomes and 
intervention.  
5. Planned interim analysis:  □yes    □v no   
 
 
 

7    Study Title: Oral Supplementation of Glutamine on Gastric Cancer Patients After 
Gastrectomy              Version date:  2022/11/03 
Appendix I: Clinical Schedule 
Period 
Screening 
Period 
Gastrectomy  
Study Drug 
Treatment 
Period 
Follow-up Period 
Postoperative Day (POD) 
-1 
0 
3~7 
31~35 
28 
56 
84 
Informed Consent 
V 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
V 
 
 
 
 
 
 
Randomization 
 
V 
 
 
 
 
 
Medical History 
V 
 
 
 
 
 
 
Gastrectomy 
 
V 
 
 
 
 
 
Blood 
laboratory 
Test  
AST 
V 
 
 
 
 
 
V 
ALT 
V 
 
 
 
 
 
V 
BUN 
V 
 
 
 
 
 
V 
Creatinine 
V 
 
 
 
 
 
V 
CBC, D/C 
V 
 
 
 
 
 
V 
Prealbumin 
V 
 
 
 
 
 
V 
Serum albumin 
V 
 
 
 
 
 
V 
 
CT scan 
V 
 
 
 
 
 
V 
Smart watch 
 
 
V 
V 
V 
V 
V 
Study formula Administration 
 
 
V 
V 
 
 
 
Weight Measurement  
V 
 
V 
 
 
 
V 
Adverse Events 
V 
 
V 
V 
V 
V 
V 
 
 
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