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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Intestinal Failure

Intervention / Treatment
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* Dietary Supplement: Intervention group


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, controlled clinical trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>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<br>* 0.1-0.2 g n-3 PUFA/kg body weight/day for 7 days<br>* Other names: n-3 PUFAs;|
| No Intervention: Control group<br>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?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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omega 3 polyunsaturated fatty acids, intestinal failure, oxidative stress