Back to resultsL-citrulline Supplementation During Sepsis
Primary Purpose
Sepsis, Multiple Organ Failure
Status
Unknown status
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
L-citrulline supplementation
L-alanine
Sponsored by
About this trial
This is an interventional treatment trial for Sepsis focused on measuring sepsis, microcirculation, nitric oxide, citrulline
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
Sites / Locations
- University Hospital Maastricht
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
AA
AB
Arm Description
24 ICU patients with severe sepsis will get a L-citrulline 8 h enteral supplementation.
24 ICU patients with severe sepsis will get an alternative isocaloric amino acid supplementation (L-alanine) during 8 hours
Outcomes
Primary Outcome Measures
To study stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the arginine-NO metabolism
Secondary Outcome Measures
Secondary study endpoints are the microcirculation, the vascular permeability and organ function scores.
Full Information
NCT ID
NCT00628381
First Posted
February 26, 2008
Last Updated
September 2, 2010
Sponsor
Maastricht University Medical Center
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
1. Study Identification
Unique Protocol Identification Number
NCT00628381
Brief Title
L-citrulline Supplementation During Sepsis
Official Title
Arginine and Nitric Oxide (NO) Metabolism in Sepsis; L-citrulline Enteral Supplementation for the Normalisation of the Arginine-NO Metabolism
Study Type
Interventional
2. Study Status
Record Verification Date
September 2010
Overall Recruitment Status
Unknown status
Study Start Date
January 2011 (undefined)
Primary Completion Date
January 2013 (Anticipated)
Study Completion Date
January 2013 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Maastricht University Medical Center
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Multiple Organ Failure
Keywords
sepsis, microcirculation, nitric oxide, citrulline
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AA
Arm Type
Experimental
Arm Description
24 ICU patients with severe sepsis will get a L-citrulline 8 h enteral supplementation.
Arm Title
AB
Arm Type
Active Comparator
Arm Description
24 ICU patients with severe sepsis will get an alternative isocaloric amino acid supplementation (L-alanine) during 8 hours
Intervention Type
Dietary Supplement
Intervention Name(s)
L-citrulline supplementation
Intervention Description
L-citrulline, 1.8micromol/kg/min, during 8 hours continuously supplemented
Intervention Type
Dietary Supplement
Intervention Name(s)
L-alanine
Intervention Description
L-alanine enteral infusion, isocaloric dosage (3.6 micromol/kg/min), during 8 hours, continuously supplemented
Primary Outcome Measure Information:
Title
To study stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the arginine-NO metabolism
Time Frame
8 hours
Secondary Outcome Measure Information:
Title
Secondary study endpoints are the microcirculation, the vascular permeability and organ function scores.
Time Frame
within 8 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nina Wijnands, MD, PhD-student
Phone
+31-43-3884502
Email
n.wijnands@ah.unimaas.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Martijn Poeze, MD, PhD
Phone
+31-43-3874425
Email
m.poeze@ah.unimaas.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martijn Poeze, MD, PhD
Organizational Affiliation
Department of Surgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Maastricht
City
Maastricht
State/Province
Limburg
ZIP/Postal Code
6202 AZ
Country
Netherlands
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martijn Poeze, MD, PhD
Phone
+31-43 3876543
Email
m.poeze@ah.unimaas.nl
First Name & Middle Initial & Last Name & Degree
Nina Wijnands, MD, PhD-student
Phone
+31-43-3884502
Email
n.wijnands@ah.unimaas.nl
12. IPD Sharing Statement
Citations:
PubMed Identifier
17901164
Citation
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.
Results Reference
background
PubMed Identifier
17662768
Citation
Barr 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 Reference
background
PubMed Identifier
10685071
Citation
Lehr 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.
Results Reference
background
PubMed Identifier
9806879
Citation
Wu 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.
Results Reference
background
PubMed Identifier
12135586
Citation
Hallemeesch 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.
Results Reference
background
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L-citrulline Supplementation During Sepsis
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