Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study): study protocol for a randomized, controlled, multicenter, international clinical trial

Stanislaw Klek, Cécile Chambrier, Sheldon C Cooper, Simon Gabe, Marek Kunecki, Loris Pironi, Farooq Rahman, Jacek Sobocki, Kinga Szczepanek, Geert Wanten, Nicole Lincke, Bernhard Glotzbach, Alastair Forbes, Stanislaw Klek, Cécile Chambrier, Sheldon C Cooper, Simon Gabe, Marek Kunecki, Loris Pironi, Farooq Rahman, Jacek Sobocki, Kinga Szczepanek, Geert Wanten, Nicole Lincke, Bernhard Glotzbach, Alastair Forbes

Abstract

Background: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited.

Methods/design: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs.

Discussion: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN.

Trial registration: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017.

Keywords: Chronic intestinal failure; Home parenteral nutrition; Intravenous lipid emulsion; Liver function; Omega-3 PUFA; Randomized controlled trial.

Conflict of interest statement

SK received honoraria as a lecturer from Baxter, BBraun, Fresenius-Kabi, Nestle, Nutricia and Shire. CC declares conflicting interests with Baxter and BBraun. SC received educational sponsorship from Fresenius-Kabi/Calea and Shire/Takeda and honoraria from Baxter and Novartis. SG received consultancy honoraria and funding for conferences from Takeda and Shire. MK received honoraria as a speaker from Baxter, Fresenius-Kabi, and Shire. LP received an advisory board grant from Baxter, Fresenius-Kabi and Shire, and an educational grant from SEDA. FR declares that he has no competing interests. JS received honoraria as a lecturer from Baxter, BBraun, Fresenius-Kabi, Nestle, Nutricia and Shire. KS received honoraria as a lecturer from Baxter, BBraun, Fresenius-Kabi and Nutricia. GW received research grants from Fresenius-Kabi, Baxter, BBraun and Geistlich Pharma. AF is a member of the speakers’ bureau for Baxter, BBraun, Dr Falk Pharma, and Fresenius-Kabi. NL and BG are employed by B. Braun Melsungen AG.

Figures

Fig. 1
Fig. 1
Standard Protocol Items: Recommendations for Interventional Trial (SPIRIT) Figure: HOME study visits. 1The parenteral nutrition (PN) treatment including Investigational Product (IP) will be prescribed until the final visit. If applicable, changes in prescription will be documented continuously throughout the course of the study. 2No blood samples for central laboratory analysis of fatty acid pattern in red blood cells and plasma will be taken

References

    1. Staun M, Pironi L, Bozzetti F, Baxter J, Forbes A, Joly F, et al. ESPEN Guidelines on Parenteral Nutrition: home parenteral nutrition (HPN) in adult patients. Clin Nutr. 2009;28(4):467–479. doi: 10.1016/j.clnu.2009.04.001.
    1. Pironi L, Arends J, Baxter J, Bozzetti F, Peláez RB, Cuerda C, et al. Acute Intestinal Failure Special Interest Groups of ESPEN. ESPEN endorsed recommendations. Definition and classification of intestinal failure in adults. Clin Nutr. 2015;34(2):171–180. doi: 10.1016/j.clnu.2014.08.017.
    1. Pironi L, Arends J, Bozzetti F, Cuerda C, Gillanders L, Jeppesen PB, et al. Home Artificial Nutrition and Chronic Intestinal Failure Special Interest Group of ESPEN. ESPEN guidelines on chronic intestinal failure in adults. Clin Nutr. 2016;35(2):247–307. doi: 10.1016/j.clnu.2016.01.020.
    1. Jeppesen PB, Høy CE, Mortensen PB. Essential fatty acid deficiency in patients receiving home parenteral nutrition. Am J Clin Nutr. 1998;68(1):126–133. doi: 10.1093/ajcn/68.1.126.
    1. Wanten GJ. Parenteral lipids: safety aspects and toxicity. World Rev Nutr Diet. 2015;112:63–70. doi: 10.1159/000365434.
    1. Clayton PT, Whitfield P, Iyer K. The role of phytosterols in the pathogenesis of liver complications of pediatric parenteral nutrition. Nutrition. 1998;14(1):158–164. doi: 10.1016/S0899-9007(97)00233-5.
    1. Baldermann H, Wicklmayr M, Rett K, Banholzer P, Dietze G, Mehnert H. Changes of hepatic morphology during parenteral nutrition with lipid emulsions containing LCT or MCT/LCT quantified by ultrasound. JPEN J Parenter Enteral Nutr. 1991;15(6):601–603. doi: 10.1177/0148607191015006601.
    1. Rubin M, Moser A, Vaserberg N, Greig F, Levy Y, Spivak H, et al. Structured triacylglycerol emulsion, containing both medium- and long-chain fatty acids, in long-term home parenteral nutrition: a double-blind randomized cross-over study. Nutrition. 2000;16(2):95–100. doi: 10.1016/S0899-9007(99)00249-X.
    1. Mayer K, Gokorsch S, Fegbeutel C, Hattar K, Rosseau S, Walmrath D, et al. Parenteral nutrition with fish oil modulates cytokine response in patients with sepsis. Am J Respir Crit Care Med. 2003;167(10):1321–1328. doi: 10.1164/rccm.200207-674OC.
    1. Heller AR, Rössler S, Litz RJ, Stehr SN, Heller SC, Koch R, Koch T. Omega-3 fatty acids improve the diagnosis-related clinical outcome. Crit Care Med. 2006;34(4):972–979. doi: 10.1097/01.CCM.0000206309.83570.45.
    1. Wichmann MW, Thul P, Czarnetzki HD, Morlion BJ, Kemen M, Jauch KW. Evaluation of clinical safety and beneficial effects of a fish oil containing lipid emulsion (Lipoplus, MLF541): data from a prospective, randomized, multicenter trial. Crit Care Med. 2007;35(3):700–706. doi: 10.1097/.
    1. Wang J, Yu JC, Kang WM, Ma ZQ. Superiority of a fish oil-enriched emulsion to medium-chain triacylglycerols/long-chain triacylglycerols in gastrointestinal surgery patients: a randomized clinical trial. Nutrition. 2012;28(6):623–629. doi: 10.1016/j.nut.2011.08.004.
    1. Grau-Carmona T, Bonet-Saris A, García-de-Lorenzo A, Sánchez-Alvarez C, Rodríguez-Pozo A, Acosta-Escribano J, et al. Influence of n-3 polyunsaturated fatty acids enriched lipid emulsions on nosocomial infections and clinical outcomes in critically ill patients: ICU lipids study. Crit Care Med. 2015;43(1):31–39. doi: 10.1097/CCM.0000000000000612.
    1. Eltweri A.M., Thomas A.L., Metcalfe M., Calder P.C., Dennison A.R., Bowrey D.J. Potential applications of fish oils rich in omega-3 polyunsaturated fatty acids in the management of gastrointestinal cancer. Clinical Nutrition. 2017;36(1):65–78. doi: 10.1016/j.clnu.2016.01.007.
    1. Cavicchi M, Beau P, Crenn P, Degott C, Messing B. Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med. 2000;132(7):525–532. doi: 10.7326/0003-4819-132-7-200004040-00003.
    1. Gura KM, Lee S, Valim C, Zhou J, Kim S, Modi BP, et al. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics. 2008;121(3):e678–e686. doi: 10.1542/peds.2007-2248.
    1. Goulet O, Antébi H, Wolf C, Talbotec C, Alcindor LG, Corriol O, Lamor M, et al. A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr. 2010;34(5):485–495. doi: 10.1177/0148607110363614.
    1. Diamond Ivan R., Grant Robert C., Pencharz Paul B., de Silva Nicole, Feldman Brian M., Fitzgerald Peter, Sigalet David, Dicken Bryan, Turner Justine, Marchand Valerie, Ling Simon C., Moore Aideen M., Avitzur Yaron, Wales Paul W. Preventing the Progression of Intestinal Failure–Associated Liver Disease in Infants Using a Composite Lipid Emulsion: A Pilot Randomized Controlled Trial of SMOFlipid. Journal of Parenteral and Enteral Nutrition. 2016;41(5):866–877. doi: 10.1177/0148607115626921.
    1. Mundi MS, Pattinson A, McMahon MT, Davidson J, Hurt RT. Prevalence of home parenteral and enteral nutrition in the United States. Nutr Clin Pract. 2017;32(6):799–805. doi: 10.1177/0884533617718472.
    1. Burns DL, Gill BM. Reversal of parenteral nutrition-associated liver disease with a fish oil-based lipid emulsion (Omegaven) in an adult dependent on home parenteral nutrition. JPEN J Parenter Enteral Nutr. 2013;37(2):274–280. doi: 10.1177/0148607112450301.
    1. Venecourt-Jackson E, Hill SJ, Walmsley RS. Successful treatment of parenteral nutrition-associated liver disease in an adult by use of a fish oil-based lipid source. Nutrition. 2013;29(1):356–358. doi: 10.1016/j.nut.2012.07.009.
    1. Hurt RT, Mundi MS. Use of mixed-oil fat emulsion to improve intestinal failure-associated liver disease in long-term home parenteral nutrition: A case report. JPEN J Parenter Enteral Nutr. 2017;41(1_Suppl):17S–19S. doi: 10.1177/0148607117741870.
    1. Xu Z, Li Y, Wang J, Wu B, Li J. Effect of omega-3 polyunsaturated fatty acids to reverse biopsy-proven parenteral nutrition-associated liver disease in adults. Clin Nutr. 2012;31(2):217–223. doi: 10.1016/j.clnu.2011.10.001.
    1. Mundi MS, McMahon MT, Carnell JJ, Hurt RT. Long-term use of mixed-oil lipid emulsion in adult home parenteral nutrition patients: a case series. Nutr Clin Pract. 2018;33(6):851–857. doi: 10.1002/ncp.10014.
    1. Jones CJ, Calder PC. Influence of different intravenous lipid emulsions on fatty acid status and laboratory and clinical outcomes in adult patients receiving home parenteral nutrition: a systematic review. Clin Nutr. 2018;37(1):285–291. doi: 10.1016/j.clnu.2016.12.026.
    1. Klek S, Chambrier C, Singer P, Rubin M, Bowling T, Staun M, et al. Four-week parenteral nutrition using a third generation lipid emulsion (SMOFlipid)—a double-blind, randomised, multicentre study in adults. Clin Nutr. 2013;32(2):224–231. doi: 10.1016/j.clnu.2012.06.011.
    1. Klek S, Szczepanek K, Scislo L, Walewska E, Pietka M, Pisarska M, Pedziwiatr M. Intravenous lipid emulsions and liver function in adult chronic intestinal failure patients: results from a randomized clinical trial. Nutrition. 2018;55–56:45–50. doi: 10.1016/j.nut.2018.03.008.
    1. Lehmacher W, Wassmer G, Reitmeir P. Procedures for two-sample comparison with multiple endpoints controlling the Experimentwise Error Rate. Biometrics. 1991;47:511–521. doi: 10.2307/2532142.
    1. Van Gossum A, on behalf of the ESPEN HAN&CIF group . Home artificial nutrition in Europe. In: Bozzetti F, Staun M, Van Gossum A, editors. Home parenteral nutrition. Oxon: CABI International; 2015. pp. 14–24.
    1. Tillman EM. Review and clinical update on parenteral nutrition-associated liver disease. Nutr Clin Pract. 2013;28(1):30–39. doi: 10.1177/0884533612462900.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다