"Effects of Oral Citrulline on Protein Metabolism in Healthy Humans: a Prospective, Randomized, Double-blind , Cross-over Study" (Citrugrêle)

"Effects of Oral Citrulline on Protein Metabolism in Healthy Humans: a Prospective, Randomized, Double-blind , Cross-over Study"

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 .

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: citrulline; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • CHU Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adult between 18 and 45 years of age
• Absence of any earlier supplementation with citrulline, glutamine, ornithine a-ketoglutarate, or stimol®
• Absence of any treatment with anabolic agents during the month prior to inclusion in the study- No current artificial feeding (enteral or parenteral)
• No renal, cardiac, respiratory or hepatic insufficiency
• No chronic inflammatory disease (intestinal or other
• No current corticotherapy
• Fasting blood glucose below 6mmol/L (126 mg/dL)
• Body mass index between 19 and 24.9
• Patient able to understand benefits and risks of protocol
• Not pregnant, taking oral contraceptive measure if able to procreate
• Subject affiliated to French health insurance (Sécurité Sociale)
• Informed consent form signed
• No concomitant participation to another clinical trial, and compliance with the exclusion period required by law

Exclusion Criteria:

• Subject not fulfilling inclusion criteria
• Subject mentioned in articles L1121-5 to L1121-8 of "code de la santé publique"
• Subject for whom the participation in this clinical trial would result, by cumulating stipends received for other clinical trials, in earning more than 4500 € within 12 consecutive months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 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.	Drug: citrulline; 0.06 G/kg three times/day during 7 days
Placebo Comparator: 2; 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.	Drug: placebo; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Dominique Darmaun, Professor, CHU Nantes; Study Chair: Ronan THIBAULD, Doctor, CHU Nantes

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: September 18, 2008
• First Submitted That Met QC Criteria: September 18, 2008
• First Posted (Estimate): September 19, 2008

Study Record Updates

• Last Update Posted (Estimate): March 9, 2010
• Last Update Submitted That Met QC Criteria: March 8, 2010
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Other Study ID Numbers: BRD 07/12-D