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

NCT00756080 | Completed Phase 1

• 1 other identifier: BRD 07/12-D
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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 .

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (2)

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.

Drug: citrulline

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.

Drug: placebo

Interventions

citrulline DRUG

0.06 G/kg three times/day during 7 days

1

placebo 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

2

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult between 18 and 45 years of age
• Absence of any earlier supplementation with citrulline, glutamine, ornithine a-ketoglutarate, or stimol®
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

CHU Nantes

Nantes, 44093, France

Location

MeSH Terms

Interventions

Citrulline

Intervention Hierarchy (Ancestors)

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

Study Officials

• Dominique Darmaun, Professor

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

• Ronan THIBAULD, Doctor

  Nantes University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 18, 2008
• First Posted: September 19, 2008
• Study Start: September 1, 2008
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: March 9, 2010

Record last verified: 2009-01

Locations

FR (1)