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

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ClinicalTrials.gov Identifier: NCT00149383

Recruitment Status : Completed

First Posted : September 8, 2005

Last Update Posted : April 13, 2015

Sponsor:

Collaborator:

McLaughlin-Rotman Center for Global Health, University of Toronto

Information provided by (Responsible Party):

Mahidol University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Falciparum Malaria	Drug: Rosiglitazone Drug: Placebo	Phase 1 Phase 2

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

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	140 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Randomized, Double-blind, Placebo-controlled Trial of Rosiglitazone as Adjunctive Therapy for P.Falciparum Infection
Study Start Date :	December 2004
Actual Primary Completion Date :	November 2005
Actual Study Completion Date :	January 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Drug Information available for: Rosiglitazone Rosiglitazone Maleate

Genetic and Rare Diseases Information Center resources: Malaria

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: 2	Drug: Placebo
Experimental: 1	Drug: Rosiglitazone

Outcome Measures

Primary Outcome Measures :

Time to clearance (in hours) of parasitemia from blood is recorded [ Time Frame: 5 days ]

Secondary Outcome Measures :

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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00149383

Locations

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Thailand
Faculty of Tropical Medicine, Mahidol University
Bangkok, Thailand, 10400

Sponsors and Collaborators

Mahidol University

McLaughlin-Rotman Center for Global Health, University of Toronto

Investigators

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Principal Investigator:	Kevin C Kain, MD, FRCPC	Faculty of Medicine, University of Toronto; McLaughlin-Rotman Center for Global Health, Toronto

More Information

Publications:

Suh KN, Kain KC, Keystone JS. Malaria. CMAJ. 2004 May 25;170(11):1693-702. Review.

Patel SN, Serghides L, Smith TG, Febbraio M, Silverstein RL, Kurtz TW, Pravenec M, Kain KC. CD36 mediates the phagocytosis of Plasmodium falciparum-infected erythrocytes by rodent macrophages. J Infect Dis. 2004 Jan 15;189(2):204-13. Epub 2004 Jan 9.

Serghides L, Smith TG, Patel SN, Kain KC. CD36 and malaria: friends or foes? Trends Parasitol. 2003 Oct;19(10):461-9. Review.

Smith TG, Ayi K, Serghides L, Mcallister CD, Kain KC. Innate immunity to malaria caused by Plasmodium falciparum. Clin Invest Med. 2002 Dec;25(6):262-72. Review.

Smith TG, Serghides L, Patel SN, Febbraio M, Silverstein RL, Kain KC. CD36-mediated nonopsonic phagocytosis of erythrocytes infected with stage I and IIA gametocytes of Plasmodium falciparum. Infect Immun. 2003 Jan;71(1):393-400.

Serghides L, Kain KC. Mechanism of protection induced by vitamin A in falciparum malaria. Lancet. 2002 Apr 20;359(9315):1404-6.

Serghides L, Kain KC. Peroxisome proliferator-activated receptor gamma-retinoid X receptor agonists increase CD36-dependent phagocytosis of Plasmodium falciparum-parasitized erythrocytes and decrease malaria-induced TNF-alpha secretion by monocytes/macrophages. J Immunol. 2001 Jun 1;166(11):6742-8.

McGilvray ID, Serghides L, Kapus A, Rotstein OD, Kain KC. Nonopsonic monocyte/macrophage phagocytosis of Plasmodium falciparum-parasitized erythrocytes: a role for CD36 in malarial clearance. Blood. 2000 Nov 1;96(9):3231-40.

Serghides L, Crandall I, Hull E, Kain KC. The Plasmodium falciparum-CD36 interaction is modified by a single amino acid substitution in CD36. Blood. 1998 Sep 1;92(5):1814-9.

Urquhart AD. Putative pathophysiological interactions of cytokines and phagocytic cells in severe human falciparum malaria. Clin Infect Dis. 1994 Jul;19(1):117-31. Review.

Ockenhouse CF, Ho M, Tandon NN, Van Seventer GA, Shaw S, White NJ, Jamieson GA, Chulay JD, Webster HK. Molecular basis of sequestration in severe and uncomplicated Plasmodium falciparum malaria: differential adhesion of infected erythrocytes to CD36 and ICAM-1. J Infect Dis. 1991 Jul;164(1):163-9.

Ockenhouse CF, Chulay JD. Plasmodium falciparum sequestration: OKM5 antigen (CD36) mediates cytoadherence of parasitized erythrocytes to a myelomonocytic cell line. J Infect Dis. 1988 Mar;157(3):584-8.

Oquendo P, Hundt E, Lawler J, Seed B. CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Cell. 1989 Jul 14;58(1):95-101.

Day NP, Hien TT, Schollaardt T, Loc PP, Chuong LV, Chau TT, Mai NT, Phu NH, Sinh DX, White NJ, Ho M. The prognostic and pathophysiologic role of pro- and antiinflammatory cytokines in severe malaria. J Infect Dis. 1999 Oct;180(4):1288-97.

Kwiatkowski D, Hill AV, Sambou I, Twumasi P, Castracane J, Manogue KR, Cerami A, Brewster DR, Greenwood BM. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet. 1990 Nov 17;336(8725):1201-4.

Brown H, Turner G, Rogerson S, Tembo M, Mwenechanya J, Molyneux M, Taylor T. Cytokine expression in the brain in human cerebral malaria. J Infect Dis. 1999 Nov;180(5):1742-6.

Aitman TJ, Cooper LD, Norsworthy PJ, Wahid FN, Gray JK, Curtis BR, McKeigue PM, Kwiatkowski D, Greenwood BM, Snow RW, Hill AV, Scott J. Malaria susceptibility and CD36 mutation. Nature. 2000 Jun 29;405(6790):1015-6.

Omi K, Ohashi J, Naka I, Patarapotikul J, Hananantachai H, Looareesuwan S, Tokunaga K. Polymorphisms of CD36 in Thai malaria patients. Southeast Asian J Trop Med Public Health. 2002;33 Suppl 3:1-4.

Shankar AH, Genton B, Semba RD, Baisor M, Paino J, Tamja S, Adiguma T, Wu L, Rare L, Tielsch JM, Alpers MP, West KP Jr. Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea: a randomised trial. Lancet. 1999 Jul 17;354(9174):203-9.

Schoonjans K, Auwerx J. Thiazolidinediones: an update. Lancet. 2000 Mar 18;355(9208):1008-10.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Boggild AK, Krudsood S, Patel SN, Serghides L, Tangpukdee N, Katz K, Wilairatana P, Liles WC, Looareesuwan S, Kain KC. Use of peroxisome proliferator-activated receptor gamma agonists as adjunctive treatment for Plasmodium falciparum malaria: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2009 Sep 15;49(6):841-9. doi: 10.1086/605431.

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Responsible Party:	Mahidol University
ClinicalTrials.gov Identifier:	NCT00149383 History of Changes
Other Study ID Numbers:	033-2004
First Posted:	September 8, 2005 Key Record Dates
Last Update Posted:	April 13, 2015
Last Verified:	April 2015

Keywords provided by Mahidol University:


randomized controlled trial malaria Plasmodium falciparum	thiazolidinediones rosiglitazone atovaquone-proguanil

Additional relevant MeSH terms:

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Malaria Malaria, Falciparum Protozoan Infections Parasitic Diseases	Rosiglitazone Hypoglycemic Agents Physiological Effects of Drugs

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