NCT01775020

Brief Summary

Pilot data in patients and data from pig studies indicate that arginine-NO metabolism is impaired in sepsis with changes in splanchnic metabolism and function, and reduced survival at low nitrate levels. Prolonged intravenous supplementation of L-arginine proved effective in pigs for increasing NO production, restoring gut function, and inhibiting an increase in pulmonary arterial pressure, without any deleterious systemic side effects. Prolonged intravenous L-arginine supplementation could therefore be useful in septic ICU patients.

Trial Health

100
On Track

Trial Health Score

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

Enrollment
8

participants targeted

Target at below P25 for early_phase_1

Timeline
Completed

Started Oct 2003

Longer than P75 for early_phase_1

Status
completed

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

Study Start

First participant enrolled

October 1, 2003

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2004

Completed
8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2012

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

January 21, 2013

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 24, 2013

Completed
Last Updated

January 29, 2013

Status Verified

January 1, 2013

Enrollment Period

7 months

First QC Date

January 21, 2013

Last Update Submit

January 28, 2013

Conditions

SepsisSeptic Shock

Outcome Measures

Primary Outcomes (1)

  • Nitric oxide synthesis

    Nitric oxide synthesis at step-wise increasing doses of L-arginine infusion. Following a 2h baseline measurements, 3 stepwise increasing arginine doses each provided for 2h will be tested for the effect on NO synthesis.

    8 hours

Secondary Outcomes (3)

  • hemodynamics

    8 hours

  • blood parameters

    8 hours

  • gastric perfusion

    8 hours

Study Arms (1)

L-arginine

EXPERIMENTAL

L-arginine

Dietary Supplement: L-arginine

Interventions

L-arginineDIETARY_SUPPLEMENT
Also known as: L-arginine-HCl
L-arginine

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 2 h without necessity of increasing the vasopressor dose, inotropic support or rate of fluid administration.
  • Systemic and pulmonary arterial catheters in place with continuous pressure monitoring.
  • Patients in whom the clinician is prepared to provide full life support during the duration of the study, including a life expectance of \> 24 h.

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.)
  • Corticosteroid use (prolonged intake of \> 1mg/kg daily or intake of \> 70 mg/day for 7 consecutive days within 1 month preceding the study)
  • Liver cirrhosis
  • Chronic pancreatitis
  • Diabetes mellitus type I
  • Metastases, haematological malignancies or chemotherapy
  • Patients on dialysis (CVVH or other)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (2)

  • Luiking 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.

    PMID: 19056593BACKGROUND

  • Poeze M, Bruins MJ, Kessels F, Luiking YC, Lamers WH, Deutz NE. Effects of L-arginine pretreatment on nitric oxide metabolism and hepatosplanchnic perfusion during porcine endotoxemia. Am J Clin Nutr. 2011 Jun;93(6):1237-47. doi: 10.3945/ajcn.110.007237. Epub 2011 Apr 20.

    PMID: 21508091BACKGROUND

MeSH Terms

Conditions

SepsisShock, Septic

Interventions

Arginine

Condition Hierarchy (Ancestors)

InfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsShock

Intervention Hierarchy (Ancestors)

Amino Acids, BasicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, DiaminoAmino Acids, Essential

Study Officials

  • Nicolaas E Deutz, MD PhD

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NA
Masking
NONE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 21, 2013

First Posted

January 24, 2013

Study Start

October 1, 2003

Primary Completion

May 1, 2004

Study Completion

May 1, 2012

Last Updated

January 29, 2013

Record last verified: 2013-01