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

NCT ID: NCT01386034

Last Updated: 2018-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2015-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Citrulline/Placebo

Group Type: EXPERIMENTAL

Citrulline and placebo

Intervention Type: 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.

Placebo/Citrulline

Group Type: EXPERIMENTAL

Citrulline and placebo

Intervention Type: 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.

Interventions

Citrulline and placebo

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominique DARMAUN, Pr

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

Nantes University Hospital

Nantes, , France

Clinique Saint Yves

Rennes, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 30642738 (View on PubMed)

Other Identifiers

BRD/09/05-W

Identifier Type: -

Identifier Source: org_study_id