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

Colorectal Cancer Clinical Trial

Official title:

Phase 3 Study of Enteral Nutrition Rich in Eicosapentaenoic Acid in Patients Receiving Chemotherapy for Gastric Cancer or Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01048463
• Other study ID #: EPACT
• Status: Recruiting
• Phase: Phase 3
• First received: January 12, 2010
• Last updated: October 4, 2011
• Start date: December 2009
• Est. completion date: January 2012

Study information

• Verified date: October 2011
• Source: Sun Yat-sen University
• Contact: Shi Fang, MD
• Phone: 86-0-13539951951
• Email: fangshi2008[@]yahoo.com.cn
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: January 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chemotherapy
• Colorectal Cancer
• Colorectal Neoplasms
• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Nutriall
The subjects take in 150g of Nutriall (Produced by Guangdong Academy of Agriculture Science. Every 50 grams of nutriall contains 9.3mg of VitC and 0.8mg of VitE) per day. Oral administration of the liquid is divided into 3 times per day. The treatment lasts for 21d.
• LDEPA
The subjects take in 24 pils of EPA capsule per day. The medium is gelatine. Each capsule contains 0.125g of EPA and 0.125g of olive oil. The capsules are provided by nutritional department of our institute). The treatment lasts for 21d.
• Placebo
The subjects take in 24 pils of gelatin capsule (each contains 0.25g of olive oil, provided by nutritional department of our institute) per day. The treatment lasts for 21d.
• HDEPA
The subjects take in 24 pils of EPA capsule per day. The medium is gelatine. Each capsule contains 0.25g of EPA. The capsules are provided by nutritional department of our institute). The treatment lasts for 21d.
• Chemotherapy
Oxaliplatin 135mg/m2 d1,xeloda 1000mg/m2 d1-21. (XELOX)

Locations

Country	Name	City	State
China	First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (13)

Barber MD, Fearon KC. Tolerance and incorporation of a high-dose eicosapentaenoic acid diester emulsion by patients with pancreatic cancer cachexia. Lipids. 2001 Apr;36(4):347-51. — View Citation

Bayram I, Erbey F, Celik N, Nelson JL, Tanyeli A. The use of a protein and energy dense eicosapentaenoic acid containing supplement for malignancy-related weight loss in children. Pediatr Blood Cancer. 2009 May;52(5):571-4. doi: 10.1002/pbc.21852. — View Citation

Calviello G, Di Nicuolo F, Serini S, Piccioni E, Boninsegna A, Maggiano N, Ranelletti FO, Palozza P. Docosahexaenoic acid enhances the susceptibility of human colorectal cancer cells to 5-fluorouracil. Cancer Chemother Pharmacol. 2005 Jan;55(1):12-20. Epub 2004 Sep 10. — View Citation

Crooks V, Waller S, Smith T, Hahn TJ. The use of the Karnofsky Performance Scale in determining outcomes and risk in geriatric outpatients. J Gerontol. 1991 Jul;46(4):M139-44. — View Citation

Elia M, Van Bokhorst-de van der Schueren MA, Garvey J, Goedhart A, Lundholm K, Nitenberg G, Stratton RJ. Enteral (oral or tube administration) nutritional support and eicosapentaenoic acid in patients with cancer: a systematic review. Int J Oncol. 2006 Jan;28(1):5-23. Review. — View Citation

Gorjão R, Azevedo-Martins AK, Rodrigues HG, Abdulkader F, Arcisio-Miranda M, Procopio J, Curi R. Comparative effects of DHA and EPA on cell function. Pharmacol Ther. 2009 Apr;122(1):56-64. doi: 10.1016/j.pharmthera.2009.01.004. Epub 2009 Feb 12. Review. — View Citation

Pratt VC, Watanabe S, Bruera E, Mackey J, Clandinin MT, Baracos VE, Field CJ. Plasma and neutrophil fatty acid composition in advanced cancer patients and response to fish oil supplementation. Br J Cancer. 2002 Dec 2;87(12):1370-8. — View Citation

Read JA, Beale PJ, Volker DH, Smith N, Childs A, Clarke SJ. Nutrition intervention using an eicosapentaenoic acid (EPA)-containing supplement in patients with advanced colorectal cancer. Effects on nutritional and inflammatory status: a phase II trial. Support Care Cancer. 2007 Mar;15(3):301-7. Epub 2006 Oct 5. — View Citation

Read JA, Crockett N, Volker DH, MacLennan P, Choy ST, Beale P, Clarke SJ. Nutritional assessment in cancer: comparing the Mini-Nutritional Assessment (MNA) with the scored Patient-Generated Subjective Global Assessment (PGSGA). Nutr Cancer. 2005;53(1):51-6. — View Citation

Russell ST, Tisdale MJ. Effect of eicosapentaenoic acid (EPA) on expression of a lipid mobilizing factor in adipose tissue in cancer cachexia. Prostaglandins Leukot Essent Fatty Acids. 2005 Jun;72(6):409-14. — View Citation

Wang ZD, Peng JS, Chen S, Huang ZM, Huang L. [Effects of perioperative enteral immunonutrition on nutritional status, immunity and inflammatory response of elderly patients]. Zhonghua Yi Xue Za Zhi. 2006 May 30;86(20):1410-3. Chinese. — View Citation

Yam D, Peled A, Shinitzky M. Suppression of tumor growth and metastasis by dietary fish oil combined with vitamins E and C and cisplatin. Cancer Chemother Pharmacol. 2001;47(1):34-40. — View Citation

Zhong HJ, Ying JE, Ma SL. [Effect of Supportan on nutritional status and immune function of late-staged gastric cancer patients undergoing chemotherapy]. Zhonghua Wei Chang Wai Ke Za Zhi. 2006 Sep;9(5):405-8. Chinese. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

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