Dose-response Study of Arginine Supplementation in Severe Sepsis

This study has been completed.
Sponsor:
Collaborator:
Novartis Medical Nutrition
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01775020
First received: January 21, 2013
Last updated: January 28, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Sepsis
Septic Shock
Dietary Supplement: L-arginine
Phase 0

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Arginine and Nitric Oxide (NO) Metabolism in Sepsis; Dose-response Study on the Effect of L-arginine Supplementation on NO Metabolism and Gastric Perfusion in Severe Septic Patients.

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • Nitric oxide synthesis [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • hemodynamics [ Time Frame: 8 hours ] [ Designated as safety issue: Yes ]
    Mean arterial pressure (MAP), pulmonary arterial pressure (PAP), cardiac output (CO), cardiac index (CI), heart rate (HR)

  • blood parameters [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    Blood gasses, electrolytes, glucose, insulin, amino acids, whole body protein and arginine metabolism

  • gastric perfusion [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
    Regional (gastric) CO2 production measured with tonometry (PrCO2)


Enrollment: 8
Study Start Date: October 2003
Study Completion Date: May 2012
Primary Completion Date: May 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: L-arginine
L-arginine
Dietary Supplement: L-arginine
Other Name: L-arginine-HCl

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 (see appendix A; in Dutch).
  • 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.

Exclusion Criteria:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01775020

Sponsors and Collaborators
Maastricht University Medical Center
Novartis Medical Nutrition
Investigators
Principal Investigator: Nicolaas E Deutz, MD PhD
  More Information

Publications:
Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01775020     History of Changes
Other Study ID Numbers: MEC03-139.5
Study First Received: January 21, 2013
Last Updated: January 28, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Sepsis
Shock, Septic
Toxemia
Infection
Inflammation
Pathologic Processes
Shock
Systemic Inflammatory Response Syndrome

ClinicalTrials.gov processed this record on October 23, 2014