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The specific aim of this study is to determine whether oral citrulline administration enhances whole body protein synthesis in healthy humans in the postabsorptive state. 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 |
|---|---|---|---|
| 1 | Experimental | After receiving a 7-day oral supplementation with citrulline, each subject will be admitted to the Clinical Investigation Unit for a half day, after an overnight fast,and will receive a 5-h intravenous infusion of L-[1-13C]leucine (i.e.; leucine labeled with 13C, a stable isotope of carbon) from 8 am to 1 pm. At regular intervals throughout the isotope infusion, blood will be obtained to measure 13C-enrichment in plasma a-keto-isocaproate, the keto acid of leucine, using gas chromatography-mas 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. The subject will then leave the hospital, take no treatment for13 days (wash-out period). The study will then be repeated a second time in an identical fashion, after a second 7-day period of oral supplementation with placebo, as a cross-over study design will be used. |
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| 2 | Placebo Comparator | After receiving a 7-day oral supplementation with placebo, each subject will be admitted to the Clinical Investigation Unit for a half day, after an overnight fast,and will receive a 5-h intravenous infusion of L-[1-13C]leucine (i.e.; leucine labeled with 13C, a stable isotope of carbon) from 8 am to 1 pm. At regular intervals throughout the isotope infusion, blood will be obtained to measure 13C-enrichment in plasma a-keto-isocaproate, the keto acid of leucine, using gas chromatography-mas 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. The subject will then leave the hospital, take no treatment for13 days (wash-out period). The study will then be repeated a second time in an identical fashion, after a second 7-day period of oral supplementation with citrulline, as a cross-over study design will be used. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| citrulline | Drug | 0.06 G/kg three times/day during 7 days |
| |
| placebo |
| Measure | Description | Time Frame |
|---|---|---|
| To determine whether oral citrulline administration enhances whole body protein synthesis in healthy humans in the psotabsorptive state, as measured using an intravenous infusion of stable isotope labeled leucine |
| Measure | Description | Time Frame |
|---|---|---|
| Using a 12-h urine collection, to confirm the positive effect of oral citrulline administration on nitrogen balance observed in preliminary studies (Rougé et al, Am J Physiol 293:G1061, 2007) | ||
| 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, Professor | Nantes University Hospital | Principal Investigator |
| Ronan THIBAULD, Doctor | Nantes University Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Nantes | Nantes | 44093 | France |
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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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| Drug |
placebo (equimolar mixture of 6 non essential amino acids: alanine, aspartate, glycine, histidine, proline, serine) 0,006 g/kg 3 times/day during 7 days |
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