Intestinal FailurePhase 3CITRUGRELE 2NCT01386034
Effects of Oral Citrulline on Protein Metabolism in Patients With Intestinal Failure (Citrugrêle 2)
A Phase 3 study of Intestinal Failure, run by Nantes University Hospital at 2 sites in France.
Trial summary
The specific aim of this study is to determine whether oral citrulline administration enhances whole body protein synthesis in patients with intestinal failure. 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 75 years
- Conditions the study is for
- Intestinal Failure
- 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
- 11 participants
- Where
- 2 sitesFrance
- Study dates
- Jul 2012to Jul 2015
- Phase
- Phase 3
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult between 18 and 75 years
- Patient with short bowel syndrome
- Patient with an incompetent small intestine after intestinal resection
- Patient fed orally and beyond more than 6 weeks after surgery
- Absence of any earlier supplementation with citrulline, glutamine, ornithine a-ketoglutarate, or stimol®
- No current artificial feeding (parenteral)
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- No low-sodium diet- No renal, cardiac, respiratory or hepatic insufficiency
- No chronic inflammatory disease (intestinal or other)
- No current corticosteroid treatment
- Fasting blood glucose below 6mmol/L
- Patient able to understand benefits and risks of protocol
- Women who are of childbearing potential must have a negative serum pregnancy test and agree to use a medically acceptable method of contraception throughout the study and for 15 days following the end of the study
- Signed informed consent
Who cannot join
- Subject not fulfilling inclusion criteria
- Subject mentioned in articles L1121-5 to L1121-8 of "code de la santé publique"
- Pregnancy
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Effects of Oral Citrulline on Protein Metabolism in Patients With Intestinal Failure : 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 patients with intestinal failure. 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
- Intestinal Failure
- Being tested
- Citrulline and placebo
- Keywords
- Nutrition, protein metabolism, stable isotopes, mass spectrometry, intestinal failure
- Medical subject headings
- Intestinal Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Citrulline and placeboDrug
After receiving a 7-day oral supplementation with either citrulline or placebo, each subject will be admitted for a half day, after an overnight fast, and will receive a 5-h intravenous infusion of L-[1-13C]leucine. At regular intervals throughout the isotope infusion, blood will be obtained to measure 13C-enrichment in plasma a-keto-isocaproate, using gas chromatography-mass 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. Then the subject take no treatment for 13 days. The study will then be repeated a second time in an identical fashion, after a second 7-day period of oral supplementation with either citrulline or placebo.
| Study group | Role | What they receive |
|---|---|---|
| Citrulline/Placebo | Experimental | Not described Receives: Drug: Citrulline and placebo |
| Placebo/Citrulline | Experimental | Not described Receives: Drug: Citrulline and placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
whole body protein synthesis
To determine whether oral citrulline administration enhances whole body protein synthesis in patients with intestinal insufficiency, as measured using an intravenous infusion of stable isotope labelled leucine.
Secondary outcomes (3)
nitrogen balance
Using a 6-h urine collection, to determine the effect of oral citrulline administration on nitrogen balance
Measure of insulin
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
Measure of insulin-like-growth factor 1 (IGF-1)
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 posted30 Jun 2011 (estimated)
- Study startJul 2012
- Primary completionJul 2015
- Study completionJul 2015
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 Intestinal FailureStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dominique DARMAUN, Pr, Principal investigator, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01386034
- Sponsor's protocol ID
- BRD/09/05-W
- Acronym
- CITRUGRELE 2
- Status last verified
- May 2016
- First submitted
- 24 Jun 2011
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
Publications
Jirka A, Layec S, Picot D, Bernon-Ferreira S, Grasset N, Flet L, Thibault R, Darmaun D. Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study. Clin Nutr. 2019 Dec;38(6):2599-2606. doi: 10.1016/j.clnu.2018.12.030. Epub 2019 Jan 2.
PubMed 30642738
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 Patients With Intestinal Failure : a Prospective, Randomized, Double-blind, Cross-over Study
- ClinicalTrials.gov ID
- NCT01386034
- Acronym / sponsor ID
- CITRUGRELE 2 / BRD/09/05-W
- Conditions
- Intestinal Failure
- Keywords
- Nutrition, protein metabolism, stable isotopes, mass spectrometry, intestinal failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 30 Jun 2011 (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 patients with intestinal failure. 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 |
|---|---|---|
| Citrulline/Placebo | Experimental | Drug: Citrulline and placebo |
| Placebo/Citrulline | Experimental | Drug: Citrulline and placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Adult between 18 and 75 years
- Patient with short bowel syndrome
- Patient with an incompetent small intestine after intestinal resection
- Patient fed orally and beyond more than 6 weeks after surgery
- Absence of any earlier supplementation with citrulline, glutamine, ornithine a-ketoglutarate, or stimol®
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"
- Pregnancy
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 |
|---|---|---|
| Citrulline and placeboAfter receiving a 7-day oral supplementation with either citrulline or placebo, each subject will be admitted for a half day, after an overnight fast, and will receive a 5-h intravenous infusion of L-[1-13C]leucine. At regular intervals throughout the isotope infusion, blood will be obtained to measure 13C-enrichment in plasma a-keto-isocaproate, using gas chromatography-mass 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. Then the subject take no treatment for 13 days. The study will then be repeated a second time in an identical fashion, after a second 7-day period of oral supplementation with either citrulline or placebo. | Drug | Citrulline/Placebo, Placebo/Citrulline |
Primary outcome
whole body protein synthesis
To determine whether oral citrulline administration enhances whole body protein synthesis in patients with intestinal insufficiency, as measured using an intravenous infusion of stable isotope labelled leucine.
3 secondary outcomes
nitrogen balance
Measure of insulin
Measure of insulin-like-growth factor 1 (IGF-1)
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 30642738Jirka A, Layec S, Picot D, Bernon-Ferreira S, Grasset N, Flet L, Thibault R, Darmaun D. Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study. Clin Nutr. 2019 Dec;38(6):2599-2606. doi: 10.1016/j.clnu.2018.12.030. Epub 2019 Jan 2.
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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, Pr principal investigator
Nantes University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study of Intestinal Failure, run by Nantes University Hospital at 2 sites 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 2 sites 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
whole body protein synthesis. 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 NCT01386034, 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.