NCT00628381

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
48

participants targeted

Target at below P25 for phase_3 sepsis

Timeline
Completed

Started Jan 2011

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 26, 2008

Completed
8 days until next milestone

First Posted

Study publicly available on registry

March 5, 2008

Completed
2.8 years until next milestone

Study Start

First participant enrolled

January 1, 2011

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2013

Completed
Last Updated

September 3, 2010

Status Verified

September 1, 2010

Enrollment Period

2 years

First QC Date

February 26, 2008

Last Update Submit

September 2, 2010

Conditions

Keywords

sepsismicrocirculationnitric oxidecitrulline

Outcome Measures

Primary Outcomes (1)

  • To study stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the arginine-NO metabolism

    8 hours

Secondary Outcomes (1)

  • Secondary study endpoints are the microcirculation, the vascular permeability and organ function scores.

    within 8 hours

Study Arms (2)

AA

EXPERIMENTAL

24 ICU patients with severe sepsis will get a L-citrulline 8 h enteral supplementation.

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

Dietary Supplement: L-alanine

Interventions

L-citrulline, 1.8micromol/kg/min, during 8 hours continuously supplemented

AA
L-alanineDIETARY_SUPPLEMENT

L-alanine enteral infusion, isocaloric dosage (3.6 micromol/kg/min), during 8 hours, continuously supplemented

AB

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written informed consent from close relative
  • Age \> 18 years
  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital Maastricht

Maastricht, Limburg, 6202 AZ, Netherlands

Location

Related Publications (5)

  • 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.

    PMID: 17901164BACKGROUND
  • 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.

    PMID: 17662768BACKGROUND
  • 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.

    PMID: 10685071BACKGROUND
  • 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.

    PMID: 9806879BACKGROUND
  • 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.

    PMID: 12135586BACKGROUND

MeSH Terms

Conditions

SepsisMultiple Organ Failure

Interventions

Alanine

Condition Hierarchy (Ancestors)

InfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsShock

Intervention Hierarchy (Ancestors)

Amino AcidsAmino Acids, Peptides, and Proteins

Study Officials

  • Martijn Poeze, MD, PhD

    Department of Surgery

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Nina Wijnands, MD, PhD-student

CONTACT

Martijn Poeze, MD, PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

February 26, 2008

First Posted

March 5, 2008

Study Start

January 1, 2011

Primary Completion

January 1, 2013

Study Completion

January 1, 2013

Last Updated

September 3, 2010

Record last verified: 2010-09

Locations