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

This study has been completed.
Sponsor:
Information provided by:
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT00756080
First received: September 18, 2008
Last updated: March 8, 2010
Last verified: January 2009
  Purpose

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 .


Condition Intervention Phase
Healthy Subjects
Drug: citrulline
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: "Effects of Oral Citrulline on Protein Metabolism in Healthy Humans: a Prospective, Randomized, Double-blind , Cross-over Study"

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: September 2008
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00756080

Locations
France
CHU Nantes
Nantes, France, 44093
Sponsors and Collaborators
Nantes University Hospital
Investigators
Principal Investigator: Dominique Darmaun, Professor CHU Nantes
Study Chair: Ronan THIBAULD, Doctor CHU Nantes
  More Information

No publications provided

Responsible Party: Dominique DARMAUN, Nantes University Hospital
ClinicalTrials.gov Identifier: NCT00756080     History of Changes
Other Study ID Numbers: BRD 07/12-D
Study First Received: September 18, 2008
Last Updated: March 8, 2010
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

ClinicalTrials.gov processed this record on July 20, 2014