Dose-response Study of Arginine Supplementation in Severe Sepsis

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.

Status

Completed

Phases

Early Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01775020

Enrollment

Registered

2013-01-24

Start date

2003-10-31

Completion date

2012-05-31

Last updated

2013-01-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Sepsis, Septic Shock

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.

Interventions

DIETARY_SUPPLEMENTL-arginine

Study design

Allocation

Intervention model

SINGLE_GROUP

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Nitric oxide synthesis	8 hours	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

Measure	Time frame	Description
hemodynamics	8 hours	Mean arterial pressure (MAP), pulmonary arterial pressure (PAP), cardiac output (CO), cardiac index (CI), heart rate (HR)
blood parameters	8 hours	Blood gasses, electrolytes, glucose, insulin, amino acids, whole body protein and arginine metabolism
gastric perfusion	8 hours	Regional (gastric) CO2 production measured with tonometry (PrCO2)

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026