Arginine Malaria Trial: Study of Adjunctive Arginine in Falciparum Malaria

This study has been completed.
Sponsor:
Collaborators:
Wellcome Trust
National Health and Medical Research Council, Australia
MSHR
National Institute of Health Research and Development (NIHRD), Indonesia
Rumah Sakit Mitra Masyarakat Hospital
University of Utah
University of Sydney
Information provided by:
Menzies School of Health Research
ClinicalTrials.gov Identifier:
NCT00147368
First received: September 6, 2005
Last updated: May 30, 2008
Last verified: May 2008
  Purpose

Acute falciparum malaria is associated with low plasma arginine and impaired nitric oxide (NO) production. Both are associated with poor outcome. This study will examine the safety and effect of escalating doses of arginine in falciparum malaria. It will determine whether arginine can increase NO production and have an effect on NO-dependent physiological measurements. The hypothesis is that arginine: will be safe in falciparum malaria; will return plasma arginine concentration to normal/supranormal levels; will increase systemic and exhaled NO; reduces oxidant stress; and improves a number of NO-dependent physiological measures of relevance to malaria.


Condition Intervention Phase
Malaria, Falciparum
Drug: intravenous (IV) arginine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic-Pharmacodynamic Study of Adjunctive Arginine in Falciparum Malaria

Resource links provided by NLM:


Further study details as provided by Menzies School of Health Research:

Primary Outcome Measures:
  • exhaled and systemic nitric oxide production
  • endothelial function

Secondary Outcome Measures:
  • safety
  • pharmacokinetic (PK) parameters
  • pharmacodynamic (PD) parameters
  • oxidant stress
  • gas transfer
  • endothelial activation
  • a priori subgroup analysis: endothelial function in those with baseline impairment of function

Estimated Enrollment: 50
Study Start Date: February 2005
Study Completion Date: December 2007
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ages 18-60 years
  2. P. falciparum parasitemia (1,000-100,000 parasites/ul).
  3. Clinical syndrome consistent with malaria associated with documented fever (axillary temperature > 38℃) or self-reported history of fever in the last 48 hours with no other cause present
  4. Commenced oral quinine ≤ 18 hours prior to scheduled commencement of arginine
  5. An indication for hospital admission (eg relative cannot look after/supervise treatment at home but not having any warning signs or severe malaria criteria in "exclusion criteria" below)
  6. Informed consent obtained

Exclusion Criteria:

  1. Pregnancy or lactation
  2. Mixed infection with P. falciparum and P. vivax
  3. Warning signs of altered mental state and inability to sit unaided
  4. Features of severe/complicated malaria
  5. Diabetes
  6. Systolic blood pressure (BP) < 100 mmHg
  7. Serious underlying disease (cardiac, hepatic, kidney)
  8. Initial iSTAT test showing any of the following values:

    • glucose < 4 mmol/L;
    • K+ ≥ 4.2 meq/L;
    • Cl- > 106 meq/L;
    • HCO3- < 20 meq/L.
  9. Known allergy to L-arginine
  10. Concurrent therapy with any of the following medications:

    • spironolactone;
    • oral nitrates;
    • phosphodiesterase inhibitor (eg sildenafil [Viagra]);
    • alpha-blocking antihypertensive agents (eg prazosin);
    • L-arginine.
  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: NCT00147368

Locations
Indonesia
RSMM Hospital
Timika, Indonesia
Sponsors and Collaborators
Menzies School of Health Research
Wellcome Trust
National Health and Medical Research Council, Australia
MSHR
National Institute of Health Research and Development (NIHRD), Indonesia
Rumah Sakit Mitra Masyarakat Hospital
University of Utah
University of Sydney
Investigators
Principal Investigator: Nick M Anstey, MBBS MSHR
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Nicholas Anstey, Menzies School of Health Research
ClinicalTrials.gov Identifier: NCT00147368     History of Changes
Other Study ID Numbers: arginine, GR071614MA - Wellcome Trust
Study First Received: September 6, 2005
Last Updated: May 30, 2008
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by Menzies School of Health Research:
falciparum
malaria
arginine

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on August 28, 2014