Effects of Oral Citrulline on Protein Metabolism in Patients With Intestinal Failure (Citrugrêle 2)

NCT01386034 | Completed Phase 3

• 1 other identifier: BRD/09/05-W
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

The specific aim of this study is to determine whether oral citrulline administration enhances whole body protein synthesis in patients with intestinal failure. Protein metabolism will be assessed using an intravenous infusion of stable isotope labeled leucine. The investigators hypothesize that citrulline supplementation will decrease leucine oxidation without altering proteolysis, and consequently stimulate protein synthesis.

Conditions

Intestinal Failure

Keywords

Nutrition, protein metabolism, stable isotopes, mass spectrometry, intestinal failure

Outcome Measures

Primary Outcomes (1)

• whole body protein synthesis

  To determine whether oral citrulline administration enhances whole body protein synthesis in patients with intestinal insufficiency, as measured using an intravenous infusion of stable isotope labelled leucine.

Secondary Outcomes (3)

• nitrogen balance

• Measure of insulin

• Measure of insulin-like-growth factor 1 (IGF-1)

Study Arms (2)

Citrulline/Placebo

EXPERIMENTAL

Drug: Citrulline and placebo

Placebo/Citrulline

EXPERIMENTAL

Drug: Citrulline and placebo

Interventions

Citrulline and placebo DRUG

After receiving a 7-day oral supplementation with either citrulline or placebo, each subject will be admitted for a half day, after an overnight fast, and will receive a 5-h intravenous infusion of L-\[1-13C\]leucine. At regular intervals throughout the isotope infusion, blood will be obtained to measure 13C-enrichment in plasma a-keto-isocaproate, using gas chromatography-mass spectrometry. Simultaneously, 13C-enrichment will be measured in aliquots of expired air CO2 using isotope ratio mass spectrometry, and total CO2 production (VCO2) will be measured using direct calorimetry, respectively. Then the subject take no treatment for 13 days. The study will then be repeated a second time in an identical fashion, after a second 7-day period of oral supplementation with either citrulline or placebo.

Citrulline/Placebo; Placebo/Citrulline

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult between 18 and 75 years
• Patient with short bowel syndrome
• Patient with an incompetent small intestine after intestinal resection
• Patient fed orally and beyond more than 6 weeks after surgery
• Absence of any earlier supplementation with citrulline, glutamine, ornithine a-ketoglutarate, or stimol®
• No current artificial feeding (parenteral)
• No low-sodium diet- No renal, cardiac, respiratory or hepatic insufficiency
• No chronic inflammatory disease (intestinal or other)
• No current corticosteroid treatment
• Fasting blood glucose below 6mmol/L
• Patient able to understand benefits and risks of protocol
• Women who are of childbearing potential must have a negative serum pregnancy test and agree to use a medically acceptable method of contraception throughout the study and for 15 days following the end of the study
• Signed informed consent

You may not qualify if:

• Subject mentioned in articles L1121-5 to L1121-8 of "code de la santé publique"
• Pregnancy

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (2)

Nantes University Hospital

Nantes, France

Location

Clinique Saint Yves

Rennes, France

Location

Related Publications (1)

• Jirka A, Layec S, Picot D, Bernon-Ferreira S, Grasset N, Flet L, Thibault R, Darmaun D. Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study. Clin Nutr. 2019 Dec;38(6):2599-2606. doi: 10.1016/j.clnu.2018.12.030. Epub 2019 Jan 2.

  PMID: 30642738 DERIVED

MeSH Terms

Conditions

Intestinal Failure

Interventions

Citrulline

Condition Hierarchy (Ancestors)

Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Dominique DARMAUN, Pr

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2011
• First Posted: June 30, 2011
• Study Start: July 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: April 6, 2018

Record last verified: 2016-05

Locations

FR (2)