Effect of Parenteral Nutrition With n-3 PUFAs on Patients With Intestinal Failure

Randomized, double-blind, controlled clinical trial to evaluate the effect of parenteral nutrition (PN) supplemented with lipid emulsions containing 0.1-0.2 g omega 3 polyunsaturated fatty acids (n-3 PUFA)/kg body weight/day for 7 days on malondialdehyde (MDA) levels, a marker of lipoperoxidation of reactive species, compared with a control group (without n-3 PUFA) in patients with intestinal failure (IF).

Study Overview

• Status: Completed
• Conditions: Intestinal Failure
• Intervention / Treatment: Dietary supplement: Intervention group

Detailed Description

IF is the loss of intestinal function that affects the decrease in the absorption of macronutrients, water, and electrolytes, so it requires intravenous supplementation such as PN and/or intravenous fluids to maintain health and/or growth. IF type II is associated with complex infectious and metabolic complications and patients require PN for weeks or months. Long-term PN use, however, includes the risk of complications, among which a serious one is the intestinal failure-associated liver disease (1). It has been proposed that metabolic endotoxemia (2-3), inflammation (4) and oxidative stress (5) are involved in the development of this intestinal failure-associated liver disease.

Although some studies have reported beneficial effects of n-3 PUFA to prevent and reverse the liver disease associated with IF (6-7), due to its antioxidant (8-10) and anti-inflammatory activity (11-12) and in the modulation of the intestinal microbiota (13), the literature on the use of n-3 PUFA in non-critical patients with IF and PN is limited and the results have not been conclusive.

Therefore, a randomized, double-blind, controlled clinical trial to evaluate the effect of PN supplemented with lipid emulsions containing n-3 PUFA/kg body weight/day for 7 days on oxidative stress (concentrations of MDA), compared with a control group (without n-3 PUFA) will be performed.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aurora E Serralde Zúñiga, MD, PhD; Phone Number: 2193 525554870900; Email: aurozabeth@yahoo.com.mx

Study Locations

• Mexico
  • Tlalpan
    • Ciudad de México, Tlalpan, Mexico, 14080
      • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients admitted in the non-critical areas of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) with a nutritional risk between January 2019 and July 2020 will be considered eligible.
• Patients with recent diagnosis of IF type II (an evolution >28 days) originate from various gastrointestinal or systemic diseases (short bowel, intestinal fistula, intestinal dysmotility, mechanical obstruction, and extensive small bowel mucosal disease).

Exclusion Criteria:

• Patients with contraindications for PN
• Patients with known allergies to the components of the PN formula
• Severe liver or renal insufficiency
• Uncontrolled diabetes mellitus
• Certain acute and life-threatening conditions
• Immunological diseases (such as autoimmune diseases, human immunodeficiency virus infection, cancer, etc.)
• Those that take immunosuppressant medications
• Severe hemorrhagic disorders
• Pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; We will use ~0.8-0.9 g/kg/day of Clinoleic® (80% olive oil/20 soybean oil) + 0.2-0.1 g/kg/day [Omegaven® ](100% fish oil), to cover the proposed amount of n-3 PUFAs for 7 days. The infusion rate should not exceed 0.5 ml Omegaven® / kg body weight / hour = 0.05 g fish oil / kg body weight / hour. The intervention group will return to PN without n-3 PUFA after 7 days.	Dietary supplement: Intervention group; 0.1-0.2 g n-3 PUFA/kg body weight/day for 7 days; Other Names: n-3 PUFAs
No Intervention: Control group; Will be administering ~1.0 g/kg/d the lipid emulsion Clinoleic® (80% olive oil/20 soybean oil) without n-3 PUFAs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of malondialdehyde (MDA) in serum from baseline to day 7	Measurement of malondialdehyde (MDA) that is a marker for oxidative stress, determined in serum in ng/dl.	Change from baseline (day 0) at day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of glutathione (GSH) in plasma from baseline to day 7	Measurement of glutathione (GSH) that is a marker for oxidative stress, determined in plasma in micromol/l.	Change from baseline (day 0) at day 7
Change of oxidized glutathione (GSSG) in plasma from baseline to day 7	Measurement of oxidized glutathione (GSSG) that is a marker for oxidative stress, determined in plasma in micromol/l.	Change from baseline (day 0) at day 7
Change of GSH/GSSG ratio from baseline to day 7	GSH and GSSG will be combined to report GSH/GSSG ratio in micromol/l	Change from baseline (day 0) at day 7
Change of carbonylated protein in serum from baseline to day 7.	Measurement of carbonylated protein that is a marker for oxidative stress, determined in serum in nmol/mg	Change from day 0 at day 7.
Change of lipopolysaccharide (LPS) in serum from baseline to day 7.	Measurement of lipopolysaccharide (LPS) that is a marker for metabolic endotoxemia, determined in serum in ng/dl.	Change from baseline (day 0) at day 7
Change of C-reactive protein (CRP) in serum from baseline to day 7.	Measurement of C-reactive protein (CRP) that is a marker for inflammation, determined in serum in pg/ml.	Change from baseline (day 0) at day 7
Change of glucose in serum from baseline to day 7	Concentration of glucose in serum according medical records, in mg/dl	Change from baseline (day 0) at day 7
Change of nitrogen ureic in serum from baseline to day 7	Concentration of nitrogen ureic in serum according medical records, in mg/dl	Change from baseline (day 0) at day 7
Change of urea in serum from baseline to day 7	Concentration of urea in serum according medical records, in mg/dl	Change from baseline (day 0) at day 7
Change of creatinin in serum from baseline to day 7	Concentration of creatinin in serum according medical records, in mg/dl	Change from baseline (day 0) at day 7
Change of sodium in serum from baseline to day 7	Concentration of sodium in serum according medical records, in mmol/l	Change from baseline (day 0) at day 7
Change of potassium in serum from baseline to day 7	Concentration of potassium in serum according medical records, in mmol/l	Change from baseline (day 0) at day 7
Change of phosphorus in serum from baseline to day 7	Concentration of phosphorus in serum according medical records, in mg/dl	Change from baseline (day 0) at day 7
Change of magnesium in serum from baseline to day 7	Concentration of magnesium in serum according medical records, in mg/dl	Change from baseline (day 0) at day 7
Change of total bilirubin in serum from baseline to day 7	Concentration of total bilirubin in serum according medical records, in mg/dl	Change from baseline (day 0) at day 7
Change of direct bilirubin in serum from baseline to day 7	Concentration of direct bilirubin in serum according medical records, in mg/dl	Change from baseline (day 0) at day 7
Change of indirect bilirubin in serum from baseline to day 7	Concentration of indirect bilirubin in serum according medical records, in mg/dl	Change from baseline (day 0) at day 7
Change of alanine aminotransferase in serum from baseline to day 7	Concentration of alanine aminotransferase in serum according medical records, in U/l	Change from baseline (day 0) at day 7
Change of aspartate aminotransferase in serum from baseline to day 7	Concentration of aspartate aminotransferase in serum according medical records, in U/l	Change from baseline (day 0) at day 7
Change of alkaline phosphatase in serum from baseline to day 7	Concentration of alkaline phosphatase in serum according medical records, in U/l	Change from baseline (day 0) at day 7
Frequency of patients with nutritional risk at baseline	Determine the frequency of patients with nutritional risk according the Nutritional Risk Assesment-2002 (NRS-2002) tool, in percentage.	At baseline (day 0)
Determine the type of intestinal failure at baseline.	Identify the classification of patients with intestinal failure according the ESPEN guidelines on chronic intestinal failure in adults, in percentage.	At baseline (day 0)
Frequency of primary diagnosis at baseline.	Determine the frequency of primary diagnosis according medical records, in percentage.	At baseline (day 0)
Assessment of resting energy expenditure at baseline	Measurement of resting energy expenditure at baseline with a calorimeter, in kcal/day	Baseline (day 0)
Assessment of nutritional prescription at baseline and at day 7	Determine the nutritional prescription at baseline, in kcal/day	At baseline (day 0) and at day 7
Frequency of the type and characteristics of nutritional support administered	Determine type and characteristics of nutritional support administered, according medical records, in percentage	At baseline (day 0) and at day 7
Assessment of height at baseline	Measurement of weight in centimeters	Baseline (day 0)
Assessment of weight at baseline and at the end of the follow-up	Measurement of weight in kilograms	At baseline (day 0) and at the end of the follow-up (~ at day 30)
Assessment of body mass index at baseline and at the end of the follow-up	Weight and height will be combined to report BMI in kg/m^2	At baseline (day 0) and at the end of the follow-up (~ at day 30)
Assessment of percentage of lean mass at baseline and at the end of the follow-up	Measurement of percentage of lean mass at baseline with a electric bioimpedance (InBody S10 ®).	At baseline (day 0) and at the end of the follow-up (~ at day 30)
Assessment of percentage of fat mass at baseline and at the end of the follow-up	Measurement of percentage of fat mass at baseline with a electric bioimpedance (InBody S10 ®).	At baseline (day 0) and at the end of the follow-up (~ at day 30)
Assessment of muscle function at baseline and at the end of the follow-up	Measurement of muscle function with a handgrip at baseline, in kilograms	At baseline (day 0) and at the end of the follow-up (~ at day 30)
Length of stay at hospitalization area	Determine the length of stay from the date of admission to the date of discharge from the hospitalization area, in days	From the date of admission to the date of discharge from the hospitalization area (~ at day 30)
Rate of mortality	Evaluation of frequency of mortality, in percentage	At the end of the follow-up (~ at day 30)
Frequency of intestinal failure-associated liver disease (IFALD)	Determined with the elevation in alkaline phosphatase concentrations within the first 7-14 days with parenteral nutrition, by elevation in transaminase concentrations more than 1.5 times above the upper limit of reference, or by elevation in the total bilirubin or direct bilirubin concentrations >3, 4, 6 and 12 mg / dl	From baseline (day 0) to the end of the follow-up (~ at day 30)

Collaborators and Investigators

• Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications and helpful links

General Publications

• Nandivada P, Fell GL, Gura KM, Puder M. Lipid emulsions in the treatment and prevention of parenteral nutrition-associated liver disease in infants and children. Am J Clin Nutr. 2016 Feb;103(2):629S-34S. doi: 10.3945/ajcn.114.103986. Epub 2016 Jan 20.
• Pironi L, Arends J, Baxter J, Bozzetti F, Pelaez RB, Cuerda C, Forbes A, Gabe S, Gillanders L, Holst M, Jeppesen PB, Joly F, Kelly D, Klek S, Irtun O, Olde Damink SW, Panisic M, Rasmussen HH, Staun M, Szczepanek K, Van Gossum A, Wanten G, Schneider SM, Shaffer J; Home Artificial Nutrition & Chronic Intestinal Failure; Acute Intestinal Failure Special Interest Groups of ESPEN. ESPEN endorsed recommendations. Definition and classification of intestinal failure in adults. Clin Nutr. 2015 Apr;34(2):171-80. doi: 10.1016/j.clnu.2014.08.017. Epub 2014 Sep 21.
• Korpela K, Mutanen A, Salonen A, Savilahti E, de Vos WM, Pakarinen MP. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure. JPEN J Parenter Enteral Nutr. 2017 Feb;41(2):238-248. doi: 10.1177/0148607115584388. Epub 2016 Sep 30.
• Omata J, Pierre JF, Heneghan AF, Tsao FH, Sano Y, Jonker MA, Kudsk KA. Parenteral nutrition suppresses the bactericidal response of the small intestine. Surgery. 2013 Jan;153(1):17-24. doi: 10.1016/j.surg.2012.04.001. Epub 2012 Jun 13.
• Cadenas S, Cadenas AM. Fighting the stranger-antioxidant protection against endotoxin toxicity. Toxicology. 2002 Oct 30;180(1):45-63. doi: 10.1016/s0300-483x(02)00381-5.
• Lacaille F, Gupte G, Colomb V, D'Antiga L, Hartman C, Hojsak I, Kolacek S, Puntis J, Shamir R; ESPGHAN Working Group of Intestinal Failure and Intestinal Transplantation. Intestinal failure-associated liver disease: a position paper of the ESPGHAN Working Group of Intestinal Failure and Intestinal Transplantation. J Pediatr Gastroenterol Nutr. 2015 Feb;60(2):272-83. doi: 10.1097/MPG.0000000000000586.
• 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 Mar;37(2):274-80. doi: 10.1177/0148607112450301. Epub 2012 Jun 8.
• Ventro G, Chen M, Yang Y, Harmon CM. Molecular impact of omega 3 fatty acids on lipopolysaccharide-mediated liver damage. J Pediatr Surg. 2016 Jun;51(6):1039-43. doi: 10.1016/j.jpedsurg.2016.02.078. Epub 2016 Mar 2.
• Wu G, Zhou W, Zhao J, Pan X, Sun Y, Xu H, Shi P, Geng C, Gao L, Tian X. Matrine alleviates lipopolysaccharide-induced intestinal inflammation and oxidative stress via CCR7 signal. Oncotarget. 2017 Feb 14;8(7):11621-11628. doi: 10.18632/oncotarget.14598.
• Giordano E, Visioli F. Long-chain omega 3 fatty acids: molecular bases of potential antioxidant actions. Prostaglandins Leukot Essent Fatty Acids. 2014 Jan;90(1):1-4. doi: 10.1016/j.plefa.2013.11.002. Epub 2013 Dec 3.
• Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans. 2017 Oct 15;45(5):1105-1115. doi: 10.1042/BST20160474. Epub 2017 Sep 12.
• Osowska S, Kunecki M, Sobocki J, Tokarczyk J, Majewska K, Omidi M, Radkowski M, Fisk HL, Calder PC. Effect of changing the lipid component of home parenteral nutrition in adults. Clin Nutr. 2019 Jun;38(3):1355-1361. doi: 10.1016/j.clnu.2018.05.028. Epub 2018 Jun 6.
• Laparra JM, Sanz Y. Interactions of gut microbiota with functional food components and nutraceuticals. Pharmacol Res. 2010 Mar;61(3):219-25. doi: 10.1016/j.phrs.2009.11.001. Epub 2009 Nov 13.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Actual): May 1, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: March 8, 2019
• First Posted (Actual): March 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: oxidative stress; intestinal failure; omega 3 polyunsaturated fatty acids
• Other Study ID Numbers: 2846

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No