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

Intestinal Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03869957
• Other study ID #: 2846
• Status: Completed
• Phase: N/A
• Start date: December 1, 2019
• Est. completion date: June 30, 2022

Study information

• Verified date: March 2023
• Source: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 30, 2022
• Est. primary completion date: May 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Intestinal Failure

Intervention

Dietary Supplement:
• Intervention group
0.1-0.2 g n-3 PUFA/kg body weight/day for 7 days

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán	Ciudad de México	Tlalpan

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Country where clinical trial is conducted

Mexico, 

References & Publications (13)

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: 10.1177/014860711245 — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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/ — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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 2 — View Citation

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, Sh — View Citation

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. — View Citation

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	Frequency of primary diagnosis at baseline.	Determine the frequency of primary diagnosis according medical records, in percentage.	At baseline (day 0)
Secondary	Assessment of resting energy expenditure at baseline	Measurement of resting energy expenditure at baseline with a calorimeter, in kcal/day	Baseline (day 0)
Secondary	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
Secondary	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
Secondary	Assessment of height at baseline	Measurement of weight in centimeters	Baseline (day 0)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Rate of mortality	Evaluation of frequency of mortality, in percentage	At the end of the follow-up (~ at day 30)
Secondary	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)