Safety and Efficacy of Chloroquine Associated With Dehydroepiandrosterone Sulphate to Treat Uncomplicated Falciparum Malaria

Malaria Clinical Trial

Official title:

Etude de l’Activite (Efficacite et Tolerance) de l’Association de la Chloroquine Avec la Dehydroepiandrosterone-Sulfate (Dheas) Dans le Traitement de l’Acces Palustre Simple A Plasmodium Falciparum

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT00442403
• Other study ID #: FSP 97008500
• Status: Suspended
• Phase: Phase 3
• First received: February 28, 2007
• Last updated: February 28, 2007
• Start date: April 2002
• Est. completion date: September 2002

Study information

• Verified date: February 2007
• Source: Université Victor Segalen Bordeaux 2
• Contact: n/a
• Is FDA regulated: No
• Health authority: Cameroun: National Ethical Committee, Yaounde
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate the safety and efficacy of a standard chloroquine drug regimen administration supplemented with dehydroepiandrosterone sulfate against drug-resistant malaria.

Description:

Worldwide progression of Plasmodium falciparum chloroquine (CQ), amodiaquine and sulfadoxine-pyrimethamine resistance leaves few alternative for the control of malaria, particularly in Africa. For some strains of P. falciparum and P. berghei, the resistance to CQ and AQ is linked to an increase in reduced glutathione (GSH) levels and GSH-related enzyme activity, such as glucose 6-phosphate deshydrogenase (G6PD). The pro-hormone dehydroepiandrosterone sulphate can be used to potentiate the antimalarial action of CQ on drug resistant P. falciparum strains, by inhibiting parasite G6PD activity. This hormone has a second advantage: it is metabolised in human into a series of potent immunomodulatory steroids which may be in the causal pathway that allowed the induction of protective immune responses against several infections, included malaria. This first study evaluated the tolerance and efficacy of a standard CQ regimen supplemented with dehydroepiandrosterone sulphate for the treatment of drug resistant uncomplicated falciparum malaria.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 200
• Est. completion date: September 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• signing an informed consent (informed consent was given by legal guardian for children);

• age egal or more than 15 years;

• fever (axillary temperature egal or more than 37.5 °C and less than 40°C) or a history of fever within the last 24 hours;

• no sign suggestive of other febrile illness;

• absence of signs of complicated malaria (WHO criteria);

• willingness to participate in follow-up for 14 days

• a positive thick blood film for P. falciparum without other detectable infectious microorganisms

Exclusion Criteria:

• patients taking glucocorticoids or other immuno-suppressive drugs, or indicating recent antimalarial drug history (verbal questionnaire);

• severe malaria;

• mixed infections;

• women using contraceptives;

• pregnant women;

• breast-feeding women.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• chloroquine

• dehydroepiandrosterone sulphate

Locations

Country	Name	City	State
Cameroon	Institute of Medical Research and study of Medicinal Plants, Medical Research Center	Yaounde

Sponsors (1)

Lead Sponsor	Collaborator
Université Victor Segalen Bordeaux 2

Country where clinical trial is conducted

Cameroon, 

References & Publications (6)

Ayi K, Giribaldi G, Skorokhod A, Schwarzer E, Prendergast PT, Arese P. 16alpha-bromoepiandrosterone, an antimalarial analogue of the hormone dehydroepiandrosterone, enhances phagocytosis of ring stage parasitized erythrocytes: a novel mechanism for antimalarial activity. Antimicrob Agents Chemother. 2002 Oct;46(10):3180-4. — View Citation

Kurtis JD, Mtalib R, Onyango FK, Duffy PE. Human resistance to Plasmodium falciparum increases during puberty and is predicted by dehydroepiandrosterone sulfate levels. Infect Immun. 2001 Jan;69(1):123-8. — View Citation

Leenstra T, ter Kuile FO, Kariuki SK, Nixon CP, Oloo AJ, Kager PA, Kurtis JD. Dehydroepiandrosterone sulfate levels associated with decreased malaria parasite density and increased hemoglobin concentration in pubertal girls from western Kenya. J Infect Dis. 2003 Jul 15;188(2):297-304. Epub 2003 Jul 1. — View Citation

Libonati RM, Cunha MG, Souza JM, Santos MV, Oliveira SG, Daniel-Ribeiro CT, Carvalho LJ, do Nascimento JL. Estradiol, but not dehydroepiandrosterone, decreases parasitemia and increases the incidence of cerebral malaria and the mortality in plasmodium berghei ANKA-infected CBA mice. Neuroimmunomodulation. 2006;13(1):28-35. Epub 2006 May 12. — View Citation

Libonati RM, de Mendonça BB, Maués JA, Quaresma JA, de Souza JM. Some aspects of the behavior of the hypothalamus-pituitary-adrenal axis in patients with uncomplicated Plasmodium falciparum malaria: Cortisol and dehydroepiandrosterone levels. Acta Trop. 2006 Jul;98(3):270-6. Epub 2006 Jul 17. — View Citation

Safeukui I, Mangou F, Malvy D, Vincendeau P, Mossalayi D, Haumont G, Vatan R, Olliaro P, Millet P. Plasmodium berghei: dehydroepiandrosterone sulfate reverses chloroquino-resistance in experimental malaria infection; correlation with glucose 6-phosphate dehydrogenase and glutathione synthesis pathway. Biochem Pharmacol. 2004 Nov 15;68(10):1903-10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development of any adverse event;
Primary	Rate of clinical and/or parasitological failure during the 14 days of follow up.
Secondary	Proportion of patients with positive blood smear during follow-u;
Secondary	Mean parasitemia during follow-up;
Secondary	Proportion of patients with clinical symptoms on day 3.