Arginine Malaria Trial: Study of Adjunctive Arginine in Falciparum Malaria

Malaria, Falciparum Clinical Trial

Official title:

Pharmacokinetic-Pharmacodynamic Study of Adjunctive Arginine in Falciparum Malaria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00147368
• Other study ID #: arginine
• Secondary ID: GR071614MA - Wel
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 6, 2005
• Last updated: May 30, 2008
• Start date: February 2005
• Est. completion date: December 2007

Study information

• Verified date: May 2008
• Source: Menzies School of Health Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 2007
• Est. primary completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum

Intervention

Drug:
• intravenous (IV) arginine

Locations

Country	Name	City	State
Indonesia	RSMM Hospital	Timika

Sponsors (8)

Lead Sponsor	Collaborator
Menzies School of Health Research	MSHR, National Health and Medical Research Council, Australia, National Institute of Health Research and Development (NIHRD), Indonesia, Rumah Sakit Mitra Masyarakat Hospital, University of Sydney, University of Utah, Wellcome Trust

Country where clinical trial is conducted

Indonesia, 

References & Publications (1)

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. Epub 2007 Oct 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	exhaled and systemic nitric oxide production
Primary	endothelial function
Secondary	safety
Secondary	pharmacokinetic (PK) parameters
Secondary	pharmacodynamic (PD) parameters
Secondary	oxidant stress
Secondary	gas transfer
Secondary	endothelial activation
Secondary	a priori subgroup analysis: endothelial function in those with baseline impairment of function