SepsisPhase 1/2CITRUSEPNCT02370030
Effect of Citrulline on the Clinical and Biochemical Evolution of Patients With Sepsis.
A Phase 1/2 study testing Citrulline malate in people with Sepsis, run by Instituto Mexicano del Seguro Social at 2 sites in Mexico.
Trial summary
Triple blind placebo-controlled study to determine if administering citrulline in patients with sepsis and severe sepsis slows progression to multiple organ failure and death, measuring biomarkers of endothelial dysfunction. Patients are divided into placebo or citrulline and followed up for 1 month. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Citrulline malate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 2 sitesMexico
- Study dates
- Nov 2014to Dec 2016
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sepsis
- Severe sepsis
- Diagnosis of sepsis in the first 36 hours of hospitalization.
- Informed Consent
- Intestinal tract intact
Who cannot join
- Terminal cancer
- Acute and chronic liver diseases
- Chronic renal failure.
- Acute renal failure AKIN III.
- Pregnant and postpartum women
- Dying patients.
Show all 11Show fewer
- Patients with cardiac arrest.
- Active gastrointestinal bleeding.
- Steroids or immunosuppressants.
- Enrolled in another study intervention.
- Citrulline allergy.
Trial locations and contacts
2 sites in 1 country.
Mexico2 sites, 2 recruiting
- Recruiting
CME Centro Mèdico Siglo XXI
Mexico City, Mexico City, 06720
Leonor Serrano, MS, +52-55-5627-6900 ext. 21445, leotigger40@hotmail.com
- Recruiting
CME La Raza
Mexico City, Mexico City
About this study
Official title: Controlled Randomized Multi-centric Clinical Trial on the Effect of Citrulline on the Clinical and Biochemical Evolution of Patients With Sepsis.
Triple blind placebo-controlled study to determine if administering citrulline in patients with sepsis and severe sepsis slows progression to multiple organ failure and death, measuring biomarkers of endothelial dysfunction. Patients are divided into placebo or citrulline and followed up for 1 month.
Read the detailed description
Consecutive patients with sepsis are being recited from intensive care unite of IMSS at the CMN Siglo XXI and CMN La Raza over the period of november 2015 through june 2016. After signing an informed consent they will be randomized into 80 for intervention arm and 80 for the placebo arm. All patients will receive usual medical treatment; and during seven days citurlline arm subjects will receive supplementation with oral or nasogastric citrulline (10 g/day), while other group patients will receive during seven days oral or nasogastric placebo (10 g/day) with no visible difference between these. Microalbuminuria and interleukines 1, 6, and 10 will be measured at randomization and at day 7. All subjects will be followed for 28 days, and after the follow-up period results will be analyzed to determine de efficacy and safety of citrulline, primary outcome are the incidence of multiple organic failure and death, also microalbuminuria levels 1,6,10-interleukines. We will use Student-t and Chi2 for statistical analysis.
- Conditions
- Sepsis
- Being tested
- Citrulline malate
- Keywords
- sepsis, citrulline, endothelial, toxemia, endothelial determination of progression, with vs without citrulline
- Medical subject headings
- Sepsis, Toxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Citrulline malateDietary supplement
Also called Citrulline
Active comparator: 10 g/day citrulline malate during 7 days
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Active comparator | Oral or nasogastric administration of 10 g citrulline malate daily. Blood and urine samples to determine biomarkers of endothelial damage (IL 6, IL 10 , nitric oxide and microalbuminuria), with a second sampling after 7 days of intervention. Disease severity will be measure with various scales, including APACHE II, SOFA Receives: Dietary Supplement: Citrulline malate |
| Placebo | Placebo comparator | 10 g of maltodextrin will be substituted for the citrulline. Blood and urine samples to determine biomarkers of endothelial damage (IL 6, IL 10 , nitric oxide and microalbuminuria), with a second sampling after 7 days of intervention. Disease severity will be measure with various scales, including APACHE II, SOFA Receives: Dietary Supplement: Citrulline malate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Multiple organ failure
Progression to multiple organ failure ending in death
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2015 (estimated)
- Study startNov 2014
- Primary completionJun 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Mexicano del Seguro Social
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Eduardo Almeida Gutiérrez, Instituto Mexicano del Seguro Social
- Investigators
- Eduardo Almeida Gutierrez, MSc, Study director, Coordinación de Investigación en Salud, México.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02370030
- Sponsor's protocol ID
- R-2014-785-082
- Acronym
- CITRUSEP
- Status last verified
- Aug 2015
- First submitted
- 18 Feb 2015
- Last updated
- 28 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Kao CC, Bandi V, Guntupalli KK, Wu M, Castillo L, Jahoor F. Arginine, citrulline and nitric oxide metabolism in sepsis. Clin Sci (Lond). 2009 Jun 2;117(1):23-30. doi: 10.1042/CS20080444.
PubMed 19105791Barr FE, Tirona RG, Taylor MB, Rice G, Arnold J, Cunningham G, Smith HA, Campbell A, Canter JA, Christian KG, Drinkwater DC, Scholl F, Kavanaugh-McHugh A, Summar ML. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26. doi: 10.1016/j.jtcvs.2007.02.043.
PubMed 17662768Piton G, Manzon C, Monnet E, Cypriani B, Barbot O, Navellou JC, Carbonnel F, Capellier G. Plasma citrulline kinetics and prognostic value in critically ill patients. Intensive Care Med. 2010 Apr;36(4):702-6. doi: 10.1007/s00134-010-1751-6.
PubMed 20084502Piton G, Belon F, Cypriani B, Regnard J, Puyraveau M, Manzon C, Navellou JC, Capellier G. Enterocyte damage in critically ill patients is associated with shock condition and 28-day mortality. Crit Care Med. 2013 Sep;41(9):2169-76. doi: 10.1097/CCM.0b013e31828c26b5.
PubMed 23782971Luiking YC, Poeze M, Ramsay G, Deutz NE. Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. Am J Clin Nutr. 2009 Jan;89(1):142-52. doi: 10.3945/ajcn.2007.25765. Epub 2008 Dec 3.
PubMed 19056593Kao C, Hsu J, Bandi V, Jahoor F. Alterations in glutamine metabolism and its conversion to citrulline in sepsis. Am J Physiol Endocrinol Metab. 2013 Jun 15;304(12):E1359-64. doi: 10.1152/ajpendo.00628.2012. Epub 2013 Apr 23.
PubMed 23612995Wijnands KA, Vink H, Briede JJ, van Faassen EE, Lamers WH, Buurman WA, Poeze M. Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia. PLoS One. 2012;7(5):e37439. doi: 10.1371/journal.pone.0037439. Epub 2012 May 29.
PubMed 22666356Ware LB, Magarik JA, Wickersham N, Cunningham G, Rice TW, Christman BW, Wheeler AP, Bernard GR, Summar ML. Low plasma citrulline levels are associated with acute respiratory distress syndrome in patients with severe sepsis. Crit Care. 2013 Jan 17;17(1):R10. doi: 10.1186/cc11934.
PubMed 23327349Cynober L. Citrulline: just a biomarker or a conditionally essential amino acid and a pharmaconutrient in critically ill patients? Crit Care. 2013 Mar 11;17(2):122. doi: 10.1186/cc12534.
PubMed 23509945
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Controlled Randomized Multi-centric Clinical Trial on the Effect of Citrulline on the Clinical and Biochemical Evolution of Patients With Sepsis.
- ClinicalTrials.gov ID
- NCT02370030
- Acronym / sponsor ID
- CITRUSEP / R-2014-785-082
- Conditions
- Sepsis
- Keywords
- sepsis, citrulline, endothelial, toxemia, endothelial determination of progression, with vs without citrulline
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Instituto Mexicano del Seguro SocialOther government
- Study start
- Nov 2014
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 24 Feb 2015 (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.
Triple blind placebo-controlled study to determine if administering citrulline in patients with sepsis and severe sepsis slows progression to multiple organ failure and death, measuring biomarkers of endothelial dysfunction. Patients are divided into placebo or citrulline and followed up for 1 month.
Detailed description
Consecutive patients with sepsis are being recited from intensive care unite of IMSS at the CMN Siglo XXI and CMN La Raza over the period of november 2015 through june 2016. After signing an informed consent they will be randomized into 80 for intervention arm and 80 for the placebo arm. All patients will receive usual medical treatment; and during seven days citurlline arm subjects will receive supplementation with oral or nasogastric citrulline (10 g/day), while other group patients will receive during seven days oral or nasogastric placebo (10 g/day) with no visible difference between these. Microalbuminuria and interleukines 1, 6, and 10 will be measured at randomization and at day 7. All subjects will be followed for 28 days, and after the follow-up period results will be analyzed to determine de efficacy and safety of citrulline, primary outcome are the incidence of multiple organic failure and death, also microalbuminuria levels 1,6,10-interleukines. We will use Student-t and Chi2 for statistical analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Active comparator | Dietary Supplement: Citrulline malateOral or nasogastric administration of 10 g citrulline malate daily. Blood and urine samples to determine biomarkers of endothelial damage (IL 6, IL 10 , nitric oxide and microalbuminuria), with a second sampling after 7 days of intervention. Disease severity will be measure with various scales, including APACHE II, SOFA |
| Placebo | Placebo comparator | Dietary Supplement: Citrulline malate10 g of maltodextrin will be substituted for the citrulline. Blood and urine samples to determine biomarkers of endothelial damage (IL 6, IL 10 , nitric oxide and microalbuminuria), with a second sampling after 7 days of intervention. Disease severity will be measure with various scales, including APACHE II, SOFA |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Sepsis
- Severe sepsis
- Diagnosis of sepsis in the first 36 hours of hospitalization.
- Informed Consent
- Intestinal tract intact
Key exclusion criteria (11 listed)
- Terminal cancer
- Acute and chronic liver diseases
- Chronic renal failure.
- Acute renal failure AKIN III.
- Pregnant and postpartum women
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 malateAlso: CitrullineActive comparator: 10 g/day citrulline malate during 7 days | Dietary supplement | Intervention, Placebo |
Primary outcome
Multiple organ failure
Time frame: 1 month
Progression to multiple organ failure ending in death
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2015.
- Results publication: PubMed 19105791Kao CC, Bandi V, Guntupalli KK, Wu M, Castillo L, Jahoor F. Arginine, citrulline and nitric oxide metabolism in sepsis. Clin Sci (Lond). 2009 Jun 2;117(1):23-30. doi: 10.1042/CS20080444.
- Results publication: PubMed 17662768Barr FE, Tirona RG, Taylor MB, Rice G, Arnold J, Cunningham G, Smith HA, Campbell A, Canter JA, Christian KG, Drinkwater DC, Scholl F, Kavanaugh-McHugh A, Summar ML. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26. doi: 10.1016/j.jtcvs.2007.02.043.
- Results publication: PubMed 20084502Piton G, Manzon C, Monnet E, Cypriani B, Barbot O, Navellou JC, Carbonnel F, Capellier G. Plasma citrulline kinetics and prognostic value in critically ill patients. Intensive Care Med. 2010 Apr;36(4):702-6. doi: 10.1007/s00134-010-1751-6.
- Results publication: PubMed 23782971Piton G, Belon F, Cypriani B, Regnard J, Puyraveau M, Manzon C, Navellou JC, Capellier G. Enterocyte damage in critically ill patients is associated with shock condition and 28-day mortality. Crit Care Med. 2013 Sep;41(9):2169-76. doi: 10.1097/CCM.0b013e31828c26b5.
- Results publication: PubMed 19056593Luiking YC, Poeze M, Ramsay G, Deutz NE. Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. Am J Clin Nutr. 2009 Jan;89(1):142-52. doi: 10.3945/ajcn.2007.25765. Epub 2008 Dec 3.
- Results publication: PubMed 23612995Kao C, Hsu J, Bandi V, Jahoor F. Alterations in glutamine metabolism and its conversion to citrulline in sepsis. Am J Physiol Endocrinol Metab. 2013 Jun 15;304(12):E1359-64. doi: 10.1152/ajpendo.00628.2012. Epub 2013 Apr 23.
- Results publication: PubMed 22666356Wijnands KA, Vink H, Briede JJ, van Faassen EE, Lamers WH, Buurman WA, Poeze M. Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia. PLoS One. 2012;7(5):e37439. doi: 10.1371/journal.pone.0037439. Epub 2012 May 29.
- Results publication: PubMed 23327349Ware LB, Magarik JA, Wickersham N, Cunningham G, Rice TW, Christman BW, Wheeler AP, Bernard GR, Summar ML. Low plasma citrulline levels are associated with acute respiratory distress syndrome in patients with severe sepsis. Crit Care. 2013 Jan 17;17(1):R10. doi: 10.1186/cc11934.
- Results publication: PubMed 23509945Cynober L. Citrulline: just a biomarker or a conditionally essential amino acid and a pharmaconutrient in critically ill patients? Crit Care. 2013 Mar 11;17(2):122. doi: 10.1186/cc12534.
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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.
Eduardo Almeida Gutierrez, MSc study director
Coordinación de Investigación en Salud, México.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Citrulline malate in people with Sepsis, run by Instituto Mexicano del Seguro Social at 2 sites in Mexico.
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 5 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 28 Aug 2015. 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 Mexico. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eduardo Almeida Gutierrez, MSc (+52-55-5627-6900 ext. 21230, almeida_90210@yahoo.com.mx), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Multiple organ failure (time frame: 1 month). 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 NCT02370030, which also lists 9 linked publications.
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 28 Aug 2015.