SepsisPhase 3NCT00628381
L-citrulline Supplementation During Sepsis
A Phase 3 study testing L-citrulline supplementation and L-alanine in people with Sepsis and Multiple Organ Failure, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
The purpose of this study is to study the stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the plasma citrulline concentrations and the Arginine-NO metabolism, the microcirculation, the systemic hemodynamics, vascular permeability, and organ function and disease… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Multiple Organ Failure
- What is being tested?
- L-citrulline supplementation and L-alanine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2011to Jan 2013
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent from close relative
- Age > 18 years
- Patient meets the general criteria for severe sepsis or septic shock, diagnosed less than 48 h prior to study inclusion.
- Patient must be relatively hemodynamically stable, defined as stable blood pressure (variation in mean arterial pressure <15 mm Hg) during 2h without necessity of increasing the vasopressor dose, inotropic support or rate of fluid administration.
- Systemic arterial catheter in place with continuous pressure monitoring.
- Patients in whom the clinician is prepared to provide full life support during the duration of the study
Who cannot join
- Shock due to any cause other than sepsis (e.g. drug reaction or drug overdose, pulmonary embolus, burn injury etc.)
- Prolonged or high dose corticosteroid use
- Liver cirrhosis
- Chronic pancreatitis
- Insulin-dependent diabetes mellitus
- Metastases, haematological malignancies or chemotherapy
- Patients on dialysis (CVVH or other)
- Pre-existent renal failure (on dialysis)
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
University Hospital Maastricht
Maastricht, Limburg, 6202 AZ
Martijn Poeze, MD, PhD, +31-43 3876543, m.poeze@ah.unimaas.nl
Nina Wijnands, MD, PhD-student, +31-43-3884502, n.wijnands@ah.unimaas.nl
About this study
Official title: Arginine and Nitric Oxide (NO) Metabolism in Sepsis; L-citrulline Enteral Supplementation for the Normalisation of the Arginine-NO Metabolism
The purpose of this study is to study the stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the plasma citrulline concentrations and the Arginine-NO metabolism, the microcirculation, the systemic hemodynamics, vascular permeability, and organ function and disease severity scores.
Read the detailed description
NO synthesis is compromised during sepsis through lack of arginine de novo synthesis and may thereby contribute to impaired microcirculation and organ dysfunction. Supplementation of L-citrulline in septic patients will increase NO production without increased arginase activity and these effects will be studied on arginine-NO metabolism,improved organ function, vascular permeability and microcirculation.
- Conditions
- Sepsis, Multiple Organ Failure
- Being tested
- L-citrulline supplementation, L-alanine
- Keywords
- sepsis, microcirculation, nitric oxide, citrulline
- Medical subject headings
- Sepsis, Multiple Organ Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-citrulline supplementationDietary supplement
L-citrulline, 1.8micromol/kg/min, during 8 hours continuously supplemented
L-alanineDietary supplement
L-alanine enteral infusion, isocaloric dosage (3.6 micromol/kg/min), during 8 hours, continuously supplemented
| Study group | Role | What they receive |
|---|---|---|
| AA | Experimental | 24 ICU patients with severe sepsis will get a L-citrulline 8 h enteral supplementation. Receives: Dietary Supplement: L-citrulline supplementation |
| AB | Active comparator | 24 ICU patients with severe sepsis will get an alternative isocaloric amino acid supplementation (L-alanine) during 8 hours Receives: Dietary Supplement: L-alanine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To study stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the arginine-NO metabolism
Measured: 8 hours
Secondary outcomes (1)
Secondary study endpoints are the microcirculation, the vascular permeability and organ function scores.
Measured: within 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2008 (estimated)
- Study startJan 2011
- Primary completionJan 2013 (estimated)
- Study completionJan 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Investigators
- Martijn Poeze, MD, PhD, Principal investigator, Department of Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00628381
- Sponsor's protocol ID
- MEC-08
- Other IDs
- ZON/NW 40-00806-98-114
- Status last verified
- Sep 2010
- First submitted
- 26 Feb 2008
- Last updated
- 3 Sep 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rouge C, Des Robert C, Robins A, Le Bacquer O, Volteau C, De La Cochetiere MF, Darmaun D. Manipulation of citrulline availability in humans. Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1061-7. doi: 10.1152/ajpgi.00289.2007. Epub 2007 Sep 27.
PubMed 17901164Barr 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 17662768Lehr HA, Bittinger F, Kirkpatrick CJ. Microcirculatory dysfunction in sepsis: a pathogenetic basis for therapy? J Pathol. 2000 Feb;190(3):373-86. doi: 10.1002/(SICI)1096-9896(200002)190:33.0.CO;2-3.
PubMed 10685071Wu G, Morris SM Jr. Arginine metabolism: nitric oxide and beyond. Biochem J. 1998 Nov 15;336 ( Pt 1)(Pt 1):1-17. doi: 10.1042/bj3360001.
PubMed 9806879Hallemeesch MM, Lamers WH, Deutz NE. Reduced arginine availability and nitric oxide production. Clin Nutr. 2002 Aug;21(4):273-9. doi: 10.1054/clnu.2002.0571.
PubMed 12135586
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Arginine and Nitric Oxide (NO) Metabolism in Sepsis; L-citrulline Enteral Supplementation for the Normalisation of the Arginine-NO Metabolism
- ClinicalTrials.gov ID
- NCT00628381
- Acronym / sponsor ID
- MEC-08
- Conditions
- Sepsis, Multiple Organ Failure
- Keywords
- sepsis, microcirculation, nitric oxide, citrulline
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- Jan 2011
- Primary completion
- Jan 2013 (estimated)
- Study completion
- Jan 2013 (estimated)
- First posted
- 5 Mar 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 purpose of this study is to study the stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the plasma citrulline concentrations and the Arginine-NO metabolism, the microcirculation, the systemic hemodynamics, vascular permeability, and organ function and disease severity scores.
Detailed description
NO synthesis is compromised during sepsis through lack of arginine de novo synthesis and may thereby contribute to impaired microcirculation and organ dysfunction. Supplementation of L-citrulline in septic patients will increase NO production without increased arginase activity and these effects will be studied on arginine-NO metabolism,improved organ function, vascular permeability and microcirculation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AA | Experimental | Dietary Supplement: L-citrulline supplementation24 ICU patients with severe sepsis will get a L-citrulline 8 h enteral supplementation. |
| AB | Active comparator | Dietary Supplement: L-alanine24 ICU patients with severe sepsis will get an alternative isocaloric amino acid supplementation (L-alanine) during 8 hours |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent from close relative
- Age > 18 years
- Patient meets the general criteria for severe sepsis or septic shock, diagnosed less than 48 h prior to study inclusion.
- Patient must be relatively hemodynamically stable, defined as stable blood pressure (variation in mean arterial pressure <15 mm Hg) during 2h without necessity of increasing the vasopressor dose, inotropic support or rate of fluid administration.
- Systemic arterial catheter in place with continuous pressure monitoring.
Key exclusion criteria (8 listed)
- Shock due to any cause other than sepsis (e.g. drug reaction or drug overdose, pulmonary embolus, burn injury etc.)
- Prolonged or high dose corticosteroid use
- Liver cirrhosis
- Chronic pancreatitis
- Insulin-dependent diabetes mellitus
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 |
|---|---|---|
| L-citrulline supplementationL-citrulline, 1.8micromol/kg/min, during 8 hours continuously supplemented | Dietary supplement | AA |
| L-alanineL-alanine enteral infusion, isocaloric dosage (3.6 micromol/kg/min), during 8 hours, continuously supplemented | Dietary supplement | AB |
Primary outcome
To study stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the arginine-NO metabolism
Time frame: 8 hours
1 secondary outcome
Secondary study endpoints are the microcirculation, the vascular permeability and organ function scores.
Time frame: within 8 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2010.
- Background: PubMed 17901164Rouge C, Des Robert C, Robins A, Le Bacquer O, Volteau C, De La Cochetiere MF, Darmaun D. Manipulation of citrulline availability in humans. Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1061-7. doi: 10.1152/ajpgi.00289.2007. Epub 2007 Sep 27.
- Background: 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.
- Background: PubMed 10685071Lehr HA, Bittinger F, Kirkpatrick CJ. Microcirculatory dysfunction in sepsis: a pathogenetic basis for therapy? J Pathol. 2000 Feb;190(3):373-86. doi: 10.1002/(SICI)1096-9896(200002)190:33.0.CO;2-3.
- Background: PubMed 9806879Wu G, Morris SM Jr. Arginine metabolism: nitric oxide and beyond. Biochem J. 1998 Nov 15;336 ( Pt 1)(Pt 1):1-17. doi: 10.1042/bj3360001.
- Background: PubMed 12135586Hallemeesch MM, Lamers WH, Deutz NE. Reduced arginine availability and nitric oxide production. Clin Nutr. 2002 Aug;21(4):273-9. doi: 10.1054/clnu.2002.0571.
Related trials for Sepsis
Not yet recruitingObservational study
Serum GDF-15 and LGALS3BP as Prognostic Biomarkers in Sepsis
Sepsis, Septic Shock
RecruitingPhase 3
A Trial of Adjunctive Fludrocortisone (50mcg, 100mcg or Placebo) in Critically Ill Patients With Septic Shock Receiving Hydrocortisone, Evaluating Survival and Functional Recovery and the Influence of Transcriptomic Response
Septic Shock
RecruitingObservational study
Middle East Study of Infections in Patients With Hematological Malignancies
Hematological Malignancy, Hematopoetic Stem Cell Transplantation
RecruitingObservational study
Early Detection and Kinetics of Sepsis-Induced Coagulopathy in Severe Burn Patients
Peer Bullying Intervention, Vodcast
Not yet recruitingObservational study
Comparative Study of the Genomic Characteristics of Uropathogenic Escherichia Coli According to the Severity of Community-Acquired Urinary Tract Infections in Guadeloupe (COLIGENURI)
Urinary Tract Infections
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.
Martijn Poeze, MD, PhD principal investigator
Department of Surgery
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing L-citrulline supplementation and L-alanine in people with Sepsis and Multiple Organ Failure, run by Maastricht University Medical Center at 1 site in Netherlands.
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 6 inclusion and 8 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 3 Sep 2010. 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 Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nina Wijnands, MD, PhD-student (+31-43-3884502, n.wijnands@ah.unimaas.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To study stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the arginine-NO metabolism (time frame: 8 hours). 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 NCT00628381, which also lists 5 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 3 Sep 2010.