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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Citrulline/Placebo | Experimental |
| |
| Placebo/Citrulline | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| nitrogen balance | Using a 6-h urine collection, to determine the effect of oral citrulline administration on nitrogen balance | |
| Measure of insulin | to determine whether the putative protein anabolic effect of citrulline is mediated by insulin or insulin-like-growth factor 1 (IGF-1), based on measurement of their plasma concentrations |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dominique DARMAUN, Pr | Nantes University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nantes University Hospital | Nantes | France | ||||
| Clinique Saint Yves |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30642738 | Derived | 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. |
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| ID | Term |
|---|---|
| D000090124 | Intestinal Failure |
| ID | Term |
|---|---|
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D002956 | Citrulline |
| ID | Term |
|---|---|
| D000599 | Amino Acids, Diamino |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Measure of insulin-like-growth factor 1 (IGF-1) | To determine whether the putative protein anabolic effect of citrulline is mediated by insulin or insulin-like-growth factor 1 (IGF-1), based on measurement of their plasma concentrations. |
| Rennes |
| France |