Clinical trial NCT00149383: Safety and Efficacy Study of Adjunctive Rosiglitazone in the Treatment of Uncomplicated Falciparum Malaria
Official title: A Randomized, Double-blind, Placebo-controlled Trial of Rosiglitazone as Adjunctive Therapy for P.Falciparum Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Falciparum Malaria
Keywords: randomized controlled trial
malaria
Plasmodium falciparum
thiazolidinediones
rosiglitazone
atovaquone-proguanil
Lead sponsor: Mahidol University
Sponsor class: OTHER
Collaborators: name: McLaughlin-Rotman Center for Global Health, University of Toronto
First posted: 2005-09-08
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to examine the safety, tolerability, and efficacy of adjunctive rosiglitazone in the treatment of uncomplicated P.falciparum malaria.

Detailed description: Study Rationale: Evidence suggests that if PPAR-RXR agonists (such as rosiglitazone) are used as adjunctive therapy in P. falciparum malaria infections they may increase phagocytic clearance of P. falciparum malaria, modulate deleterious inflammatory responses and decrease sequestration of malaria parasites in vital organs. They may therefore represent a novel immunomodulatory treatment approach for P. falciparum malaria.

Study Objectives: 1) To examine the in vivo effect of rosiglitazone on the rapidity of clearance of P. falciparum parasitemia and fever in patients with non-severe P. falciparum infections 2) To assess the safety and tolerability of adjunctive rosiglitazone treatment in non-severe cases of P. falciparum infection.

Primary Outcomes: Time to clearance of P. falciparum parasitemia

Study Design: Randomized double blind placebo-controlled trial.

Intervention: Standard antimalarial treatment (atovaquone/proguanil) to all patients combined with adjuvant rosiglitazone treatment (8mg per day) or placebo.

Setting: Hospital for Tropical Diseases at Mahidol University, Thailand.

Participants: 140 patients with non-severe P. falciparum infection.

Follow-up: 28 days

Eligibility criteria: Inclusion Criteria:

* Microscopically confirmed P.falciparum infection
* Age \>18 years
* Able to tolerate oral therapy
* Able to give informed consent

Exclusion Criteria:

* Fulfillment of WHO criteria for severe/cerebral malaria
* Prior treatment with any thiazolidinedione
* Allergy to rosiglitazone
* History of diabetes mellitus
* History of severe/decompensated liver disease
* ALT level \>2.5 times normal
* Current treatment for congestive heart failure
* Pregnancy or breastfeeding

Primary outcomes:
measure: Time to clearance (in hours) of parasitemia from blood is recorded
timeFrame: 5 days
Secondary outcomes:
measure: Time to resolution of fever (in hours)
timeFrame: 5 days
measure: AST/ALT levels (U/L)
timeFrame: 2 days
measure: Capillary blood glucose (mmol/L)
timeFrame: 2 days
measure: Need for ICU admission
timeFrame: 5 days
measure: Tolerability of study drug/placebo as assessed by patient log
timeFrame: 5 days
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Faculty of Tropical Medicine, Mahidol University
Study officials:
affiliation: Faculty of Medicine, University of Toronto; McLaughlin-Rotman Center for Global Health, Toronto
name: Kevin C Kain, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
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