Healthy SubjectsPhase 1NCT00756080
"Effects of Oral Citrulline on Protein Metabolism in Healthy Humans: a Prospective, Randomized, Double-blind , Cross-over Study" (Citrugrêle)
A Phase 1 study testing citrulline in people with Healthy Subjects, run by Nantes University Hospital at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects
- What is being tested?
- citrulline
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2008to Jan 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: "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 .
- Conditions
- Healthy Subjects
- Being tested
- citrulline, placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
citrullineDrug
0.06 G/kg three times/day during 7 days
placeboDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2008 (estimated)
- Study startSep 2008
- Primary completionJan 2009
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy SubjectsStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Dominique Darmaun, Professor, Principal investigator, Nantes University HospitalRonan THIBAULD, Doctor, Study chair, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00756080
- Sponsor's protocol ID
- BRD/07/12-D
- Status last verified
- Jan 2009
- First submitted
- 18 Sep 2008
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
Publications
Thibault R, Flet L, Vavasseur F, Lemerle M, Ferchaud-Roucher V, Picot D, Darmaun D. Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over study. Clin Nutr. 2011 Dec;30(6):807-11. doi: 10.1016/j.clnu.2011.06.005. Epub 2011 Jul 5.
PubMed 21733603
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Effects of Oral Citrulline on Protein Metabolism in Healthy Humans: a Prospective, Randomized, Double-blind , Cross-over Study"
- ClinicalTrials.gov ID
- NCT00756080
- Acronym / sponsor ID
- BRD/07/12-D
- Conditions
- Healthy Subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 19 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: citrullineAfter 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. |
| 2 | Placebo comparator | Drug: placeboAfter 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| citrulline0.06 G/kg three times/day during 7 days | Drug | 1 |
| placeboplacebo (equimolar mixture of 6 non essential amino acids: alanine, aspartate, glycine, histidine, proline, serine) 0,006 g/kg 3 times/day during 7 days | Drug | 2 |
Primary outcome
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
2 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Results publication: PubMed 21733603Thibault R, Flet L, Vavasseur F, Lemerle M, Ferchaud-Roucher V, Picot D, Darmaun D. Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over study. Clin Nutr. 2011 Dec;30(6):807-11. doi: 10.1016/j.clnu.2011.06.005. Epub 2011 Jul 5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominique Darmaun, Professor principal investigator
Nantes University Hospital
Ronan THIBAULD, Doctor study chair
Nantes University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing citrulline in people with Healthy Subjects, run by Nantes University Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00756080, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.