Study of the Effect of Glutamine Supplementation on Chemotherapy Induced Toxicities in Breast Cancer Patients

Overview

Glutamine, a non essential branched chain amino acid, is most important non toxic nitrogen carrier in body. It participates in variety of physiological functions. It is a major fuel source of enterocytes and is a substrate for gluconeogenesis in kidney, lymphocytes, and monocytes. It is also a nutrient in muscle protein metabolism in response to infection, inflammation and muscle trauma. The significance of glutamine to metabolic homeostasis becomes evident during periods of stress, when it becomes a conditionally essential amino acid. Role of glutamine as protective agent in hepato-biliary dysfunction, in maintaining mucosal integrity of the Gastrointestinal tract following its administration in patient with major bowel surgery as a supplement and part of TPN in critically ill patients and in patients of septicemia, is well established. However the role of glutamine supplementation in reducing or preventing chemotherapeutic agents induced toxicity in cancer patients is controversial.

Full Title of Study: “Study of the Effect of Glutamine Supplementation on Chemotherapy Induced Toxicities in Breast Cancer Patients- A Prospective, Randomised, Single Blind, Three Arm, Phase Four Prevention Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Single (Participant)
  • Study Primary Completion Date: December 2009

Interventions

  • Dietary Supplement: Glutamine
    • 2g/kg body weight twice daily in divided doses for 5 days
  • Dietary Supplement: IV Glutamine
    • 50 ml of 20% glutamine IV before chemotherapy

Arms, Groups and Cohorts

  • No Intervention: 1
    • 10 patients (30 cycles) of chemotherapy will receive placebo
  • Active Comparator: 2
    • Intravenous glutamine
  • Experimental: 3
    • Oral Glutamine

Clinical Trial Outcome Measures

Primary Measures

  • Reduction in toxicity
    • Time Frame: 3 weeks

Secondary Measures

  • Serum level of creatinine kinase and LDH
    • Time Frame: 3 weeks

Participating in This Clinical Trial

Inclusion Criteria

  • The patients > 18 years of age – Histologically or cytologically proven breast cancer – Receiving CEF chemotherapy cycles presently or in the past – The patients who will give informed consent to participate in the study – Patients must have sufficient organ and marrow function – Stage 1 neuropathy, subclinical neuropathy, surgery induced neuropathy Exclusion Criteria:

  • Pregnancy – Clinical/biochemical severe liver failure – Clinical/biochemical severe renal dysfunction – Refusal to participate in the study – Patients who have received prior chemotherapy with paclitaxel. – Patients who have neuropathy due to any known systemic or metabolic causes like diabetes, leprosy, nutritional deficiency induced (vit. B12) etc

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Banaras Hindu University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Manoj Pandey, Professor, Surgical Oncology – Banaras Hindu University
  • Overall Official(s)
    • R K Goel, MD, Principal Investigator, Institute of Medical Sciences

References

Bergstrom J, Furst P, Noree LO, Vinnars E. Intracellular free amino acid concentration in human muscle tissue. J Appl Physiol. 1974 Jun;36(6):693-7. doi: 10.1152/jappl.1974.36.6.693. No abstract available.

Lacey JM, Wilmore DW. Is glutamine a conditionally essential amino acid? Nutr Rev. 1990 Aug;48(8):297-309. doi: 10.1111/j.1753-4887.1990.tb02967.x.

Daniele B, Perrone F, Gallo C, Pignata S, De Martino S, De Vivo R, Barletta E, Tambaro R, Abbiati R, D'Agostino L. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut. 2001 Jan;48(1):28-33. doi: 10.1136/gut.48.1.28.

Rubio IT, Cao Y, Hutchins LF, Westbrook KC, Klimberg VS. Effect of glutamine on methotrexate efficacy and toxicity. Ann Surg. 1998 May;227(5):772-8; discussion 778-80. doi: 10.1097/00000658-199805000-00018.

Satoh J, Tsujikawa T, Fujiyama Y, Bamba T. Nutritional benefits of enteral alanyl-glutamine supplementation on rat small intestinal damage induced by cyclophosphamide. J Gastroenterol Hepatol. 2003 Jun;18(6):719-25. doi: 10.1046/j.1440-1746.2003.03042.x.

van der Hulst RR, van Kreel BK, von Meyenfeldt MF, Brummer RJ, Arends JW, Deutz NE, Soeters PB. Glutamine and the preservation of gut integrity. Lancet. 1993 May 29;341(8857):1363-5. doi: 10.1016/0140-6736(93)90939-e.

Govindarajan R, Heaton KM, Broadwater R, Zeitlin A, Lang NP, Hauer-Jensen M. Effect of thalidomide on gastrointestinal toxic effects of irinotecan. Lancet. 2000 Aug 12;356(9229):566-7. doi: 10.1016/s0140-6736(00)02586-1.

Berthrong M. Pathologic changes secondary to radiation. World J Surg. 1986 Apr;10(2):155-70. doi: 10.1007/BF01658133. No abstract available.

Huang EY, Leung SW, Wang CJ, Chen HC, Sun LM, Fang FM, Yeh SA, Hsu HC, Hsiung CY. Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial. Int J Radiat Oncol Biol Phys. 2000 Feb 1;46(3):535-9. doi: 10.1016/s0360-3016(99)00402-2.

Cao Y, Kennedy R, Klimberg VS. Glutamine protects against doxorubicin-induced cardiotoxicity. J Surg Res. 1999 Jul;85(1):178-82. doi: 10.1006/jsre.1999.5677.

Boyle FM, Wheeler HR, Shenfield GM. Amelioration of experimental cisplatin and paclitaxel neuropathy with glutamate. J Neurooncol. 1999 Jan;41(2):107-16. doi: 10.1023/a:1006124917643.

Vahdat L, Papadopoulos K, Lange D, Leuin S, Kaufman E, Donovan D, Frederick D, Bagiella E, Tiersten A, Nichols G, Garrett T, Savage D, Antman K, Hesdorffer CS, Balmaceda C. Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res. 2001 May;7(5):1192-7.

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