NCT00147368

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
50

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Feb 2005

Typical duration for phase_1

Geographic Reach
1 country

1 active site

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

February 1, 2005

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

September 6, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 7, 2005

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2006

Completed
1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2007

Completed
Last Updated

June 2, 2008

Status Verified

May 1, 2008

Enrollment Period

1.2 years

First QC Date

September 6, 2005

Last Update Submit

May 30, 2008

Conditions

Malaria, Falciparum

Keywords

falciparummalariaarginine

Outcome Measures

Primary Outcomes (2)

  • exhaled and systemic nitric oxide production

  • endothelial function

Secondary Outcomes (7)

  • safety

  • pharmacokinetic (PK) parameters

  • pharmacodynamic (PD) parameters

  • oxidant stress

  • gas transfer

  • +2 more secondary outcomes

Interventions

intravenous (IV) arginineDRUG

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Ages 18-60 years
  • P. falciparum parasitemia (1,000-100,000 parasites/ul).
  • 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
  • Commenced oral quinine ≤ 18 hours prior to scheduled commencement of arginine

You may not qualify if:

  • Informed consent obtained
  • Pregnancy or lactation
  • Mixed infection with P. falciparum and P. vivax
  • Warning signs of altered mental state and inability to sit unaided
  • Features of severe/complicated malaria
  • Diabetes
  • Systolic blood pressure (BP) \< 100 mmHg
  • Serious underlying disease (cardiac, hepatic, kidney)
  • 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.
  • Known allergy to L-arginine
  • Concurrent therapy with any of the following medications:
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

RSMM Hospital

Timika, Indonesia

Location

Related Publications (2)

  • Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, McNeil YR, Darcy CJ, Granger DL, Weinberg JB, Lopansri BK, Price RN, Duffull SB, Celermajer DS, Anstey NM. Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria. J Exp Med. 2007 Oct 29;204(11):2693-704. doi: 10.1084/jem.20070819. Epub 2007 Oct 22.

    PMID: 17954570BACKGROUND

  • Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, Granger DL, Weinberg JB, Lopansri BK, Price RN, Celermajer DS, Duffull SB, Anstey NM. Safety profile of L-arginine infusion in moderately severe falciparum malaria. PLoS One. 2008 Jun 11;3(6):e2347. doi: 10.1371/journal.pone.0002347.

    PMID: 18545693DERIVED

MeSH Terms

Conditions

Malaria, FalciparumMalaria

Interventions

Arginine

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

  • Nick M Anstey, MBBS

    MSHR

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

September 6, 2005

First Posted

September 7, 2005

Study Start

February 1, 2005

Primary Completion

April 1, 2006

Study Completion

December 1, 2007

Last Updated

June 2, 2008

Record last verified: 2008-05

Locations

ID(1)