Effect of Enteral Nutrition Rich in Eicosapentaenoic Acid (EPA) on Patients Receiving Chemotherapy for GI Tumor

Phase 3

• Conditions: Gastric Cancer; Colorectal Cancer; Chemotherapy
• Interventions: Drug: Nutriall; Drug: Placebo; Drug: LDEPA; Drug: HDEPA; Drug: Chemotherapy

• Registration Number: NCT01048463
• Lead Sponsor: Sun Yat-sen University

Brief Summary

Malnutrition is frequently seen in patients on chemotherapy suffering from gastric/colorectal cancer and may worsen the outcome. EPA, a sort of ω-3 PUFA, can modulate immune system. EPA also antagonizes metabolic and inflammatory changes induced by the tumor. This study is to test whether EPA, in combination with enteral nutrition, can improve nutritional/immunologic status, quality of life, and reduce chemotherapy related side effects of these patients.

Detailed Description

Chemotherapy is indispensible for patients suffering from advanced gastric or colorectal cancer, and also the main therapy for those with end-stage tumor. However, incidence of malnutrition during chemotherapy was reported as high as 60%. The mechanisms include anatomy modification of digestive tract, side effects of chemotherapy such as anorexia, nausea, vomiting, and inflammatory factors generated or induced by the tumor. Malnutrition may lead to discontinuation of the therapy, compromise of the anti-cancer effect, increase of toxicity and mortality. 20%-40% of patients with end-stage tumor ultimately died from malnutrition.

EPA (Eicosapentaenoic acid, molecular formula C20H30O2) belongs to ω-3 polyunsaturated fatty acid (ω-3 PUFA). EPA is one of the main constituent of fish oil. EPA decreases LPS-stimulated macrophage production of TNF-α, IL-1β, IL-6, and human B lymphocytes production of IL-10, TNF-α, IFN-γ. EPA can suppress cancer induced lipolysis, and enhanced the inhibitory effect of 5-Fu over cancer cell proliferation. However, cancer patients are always lack of EPA.

Nutriall is a sort of non-elemental diet. The kind of powder is produced by Guangdong Academy of Agriculture Science. Every 50 grams of nutriall contains 9.3mg of VitC and 0.8mg of VitE. For this enteral nutrition preparation, there have been evidences of protective effects on nutritional status during chemotherapy on lung cancer. However, this kind of preparation does not contain EPA.

Up to date, there has been no RCT which testified whether therapeutic dosage of EPA plus enteral nutrition has combined effects on patients receiving chemotherapy. The investigators choose nutriall as basic nutritional support agent during chemotherapy, and give patients different dosage of EPA. Nutritional and immunologic status, quality of life and side effects of chemotherapy are recorded to evaluate whether EPA can improve outcome of these patients. Through this study the investigators may also optimize the dose of EPA for patients receiving chemotherapy on gastric/colorectal cancer.

Study Timeline

• Study Start: 2009-12
• Study First Submitted: 2010-01-12
• Study First Submitted QC: 2010-01-12
• Study First Posted: 2010-01-13
• Status Verified: 2011-10
• Last Update Submitted: 2011-10-04
• Last Update Posted: 2011-10-06
• Primary Completion: 2011-12
• Study Completion: 2012-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• The cases have undergone radical excision on gastric cancer or colorectal cancer.
• Without contraindication for chemotherapy.
• Eligible for postoperative adjuvant XELOX chemotherapy.
• Capable of taking in food or drug orally.
• Without severe absorption dysfunction
• Able and willing to give written, informed consent

Exclusion Criteria

• Comorbidities: diseases of hematology or immunology system; hepatic or renal dysfunction; metabolic diseases.
• BMI>35kg/m2
• Life expectancy≤3mo
• The chemotherapy treatment is palliative.
• The patient has received radiotherapy or neoadjuvant chemotherapy prior to the operation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EN	Nutriall	The subjects take in 150g of Nutriall per day. Oral administration of the liquid is divided into 3 times per day. The treatment lasts for 21d. During the test period patients are treated with the first course of XELOX.
EN	Placebo	The subjects take in 150g of Nutriall per day. Oral administration of the liquid is divided into 3 times per day. The treatment lasts for 21d. During the test period patients are treated with the first course of XELOX.
EN	Chemotherapy	The subjects take in 150g of Nutriall per day. Oral administration of the liquid is divided into 3 times per day. The treatment lasts for 21d. During the test period patients are treated with the first course of XELOX.
ENLDEPA	Nutriall	The subjects take in the same dose of Nutriall for the same duration as those in EN group. In addition, they take in 3 grams of EPA per day during the 21 days of treatment. The patients are treated with the first course of XELOX.
ENLDEPA	LDEPA	The subjects take in the same dose of Nutriall for the same duration as those in EN group. In addition, they take in 3 grams of EPA per day during the 21 days of treatment. The patients are treated with the first course of XELOX.
ENLDEPA	Chemotherapy	The subjects take in the same dose of Nutriall for the same duration as those in EN group. In addition, they take in 3 grams of EPA per day during the 21 days of treatment. The patients are treated with the first course of XELOX.
ENHDPEA	Nutriall	The subjects take in the same dose of supportan for the same duration as those in EN group. In addition, they take in 6 grams of EPA per day during the 21 days of treatment. The patients are treated with the first course of XELOX.
ENHDPEA	HDEPA	The subjects take in the same dose of supportan for the same duration as those in EN group. In addition, they take in 6 grams of EPA per day during the 21 days of treatment. The patients are treated with the first course of XELOX.
ENHDPEA	Chemotherapy	The subjects take in the same dose of supportan for the same duration as those in EN group. In addition, they take in 6 grams of EPA per day during the 21 days of treatment. The patients are treated with the first course of XELOX.

Primary Outcome Measures

Name	Time	Method
Serum level of proalbumin	The starting and ending day of the experiment for a certain subject (day1 and day21)

Secondary Outcome Measures

Name	Time	Method
Weight in light clothing	The starting and ending day of the experiment for a certain subject (day1 and day21)
Height and BMI	The starting and ending day of the experiment for a certain subject (day1 and day21)
mid upper arm circumference and triceps skinfold thickness	The starting and ending day of the experiment for a certain subject (day1 and day21)
Fat ratio and fat mass	The starting and ending day of the experiment for a certain subject (day1 and day21)
Fat-free mass, muscle mass and muscle function	The starting and ending day of the experiment for a certain subject (day1 and day21)
CD distribution of T cells	The starting and ending day of the experiment for a certain subject (day1 and day21)
Serum level of different types of immunoglobulin	The starting and ending day of the experiment for a certain subject (day1 and day21)
Serum level of different types of cytokines	The starting and ending day of the experiment for a certain subject (day1 and day21)
Serum level of Cortisol	The starting and ending day of the experiment for a certain subject (day1 and day21)
Serum level of transferrin	The starting and ending day of the experiment for a certain subject (day1 and day21)
Serum level of ALT and AST	The starting and ending day of the experiment for a certain subject (day1 and day21)
Serum level of creatine and BUN	The starting and ending day of the experiment for a certain subject (day1 and day21)
Serum level of total triglyceride, total cholesterol, LDL, HDL	The starting and ending day of the experiment for a certain subject (day1 and day21)
Records of EPA intake	The whole experiment period
Records of chemotherapy-associated side effects	The whole experiment period
Serum level of albumin	The starting and ending day of the experiment for a certain subject (day1 and day21)
Serum level of CEA, CA125, CA199	The starting and ending day of the experiment for a certain subject (day1 and day21)
Records of Nutriall intake	The whole experiment period
Records of food intake	The middle 3 days of the whole experiment period (day10, day11, day12)

Trial Locations

Locations (1)

First Affiliated Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China