Safety and Efficacy Study of Adjunctive Rosiglitazone in the Treatment of Uncomplicated Falciparum Malaria

Study Overview
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Brief Summary
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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
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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

Official Title
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A Randomized, Double-blind, Placebo-controlled Trial of Rosiglitazone as Adjunctive Therapy for P.Falciparum Infection

Conditions
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Falciparum Malaria

Intervention / Treatment
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* Drug: Rosiglitazone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 2<br> | Drug: Placebo<br> <br> |
| Experimental: 1<br> | Drug: Rosiglitazone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clearance (in hours) of parasitemia from blood is recorded |  | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to resolution of fever (in hours) |  | 5 days | 
| AST/ALT levels (U/L) |  | 2 days | 
| Capillary blood glucose (mmol/L) |  | 2 days | 
| Need for ICU admission |  | 5 days | 
| Tolerability of study drug/placebo as assessed by patient log |  | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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randomized controlled trial, malaria, Plasmodium falciparum, thiazolidinediones, rosiglitazone, atovaquone-proguanil