Clinical trial NCT00442403: Safety and Efficacy of Chloroquine Associated With Dehydroepiandrosterone Sulphate to Treat Uncomplicated Falciparum Malaria
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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: Malaria
Keywords: Malaria
Plasmodium falciparum
Chemotherapy
Chloroquine
Dehydroepiandrosterone sulphate
Lead sponsor: Université Victor Segalen Bordeaux 2
Sponsor class: OTHER
First posted: 2007-03-01
Enrollment: 200
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Development of any adverse event;
measure: Rate of clinical and/or parasitological failure during the 14 days of follow up.
Secondary outcomes:
measure: Proportion of patients with positive blood smear during follow-u;
measure: Mean parasitemia during follow-up;
measure: Proportion of patients with clinical symptoms on day 3.
Other outcomes:
Locations:
city: Yaounde
country: Cameroon
facility: Institute of Medical Research and study of Medicinal Plants, Medical Research Center
Study officials:
affiliation: Université Victor Segalen Bordeaux 2, Centre René Labusquière (Santé et Développement)
name: Michel LE BRAS, Professor
role: STUDY_DIRECTOR
affiliation: Université Victor Segalen Bordeaux 2, Pôle des Maladies Tropicale, CHU de Bordeaux
name: Pascal MILLET, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Libonati RM, de Mendonca BB, Maues 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. doi: 10.1016/j.actatropica.2006.05.008. Epub 2006 Jul 17.
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. doi: 10.1159/000093271. Epub 2006 May 12.
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. doi: 10.1016/j.bcp.2004.05.049.
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. doi: 10.1086/376508. Epub 2003 Jul 1.
citation: 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. doi: 10.1128/AAC.46.10.3180-3184.2002.
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. doi: 10.1128/IAI.69.1.123-128.2001.