NCT00149383

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
140

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Dec 2004

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2004

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

September 6, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 8, 2005

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2005

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2006

Completed
Last Updated

April 13, 2015

Status Verified

April 1, 2015

Enrollment Period

11 months

First QC Date

September 6, 2005

Last Update Submit

April 10, 2015

Conditions

Falciparum Malaria

Keywords

randomized controlled trialmalariaPlasmodium falciparumthiazolidinedionesrosiglitazoneatovaquone-proguanil

Outcome Measures

Primary Outcomes (1)

  • Time to clearance (in hours) of parasitemia from blood is recorded

    5 days

Secondary Outcomes (5)

  • 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

Study Arms (2)

2

PLACEBO COMPARATOR
Drug: Placebo

1

EXPERIMENTAL
Drug: Rosiglitazone

Interventions

RosiglitazoneDRUG
1
PlaceboDRUG
2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Faculty of Tropical Medicine, Mahidol University

Bangkok, 10400, Thailand

Location

Related Publications (21)

  • Suh KN, Kain KC, Keystone JS. Malaria. CMAJ. 2004 May 25;170(11):1693-702. doi: 10.1503/cmaj.1030418.

    PMID: 15159369BACKGROUND

  • 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. doi: 10.1086/380764. Epub 2004 Jan 9.

    PMID: 14722884BACKGROUND

  • Serghides L, Smith TG, Patel SN, Kain KC. CD36 and malaria: friends or foes? Trends Parasitol. 2003 Oct;19(10):461-9. doi: 10.1016/j.pt.2003.08.006. No abstract available.

    PMID: 14519584BACKGROUND

  • 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.

    PMID: 12516999BACKGROUND

  • 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. doi: 10.1128/IAI.71.1.393-400.2003.

    PMID: 12496189BACKGROUND

  • Serghides L, Kain KC. Mechanism of protection induced by vitamin A in falciparum malaria. Lancet. 2002 Apr 20;359(9315):1404-6. doi: 10.1016/S0140-6736(02)08360-5.

    PMID: 11978340BACKGROUND

  • 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. doi: 10.4049/jimmunol.166.11.6742.

    PMID: 11359831BACKGROUND

  • 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.

    PMID: 11050008BACKGROUND

  • 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.

    PMID: 9716613BACKGROUND

  • Urquhart AD. Putative pathophysiological interactions of cytokines and phagocytic cells in severe human falciparum malaria. Clin Infect Dis. 1994 Jul;19(1):117-31. doi: 10.1093/clinids/19.1.117.

    PMID: 7948512BACKGROUND

  • 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. doi: 10.1093/infdis/164.1.163.

    PMID: 1711552BACKGROUND

  • 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. doi: 10.1093/infdis/157.3.584. No abstract available.

    PMID: 2449507BACKGROUND

  • 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. doi: 10.1016/0092-8674(89)90406-6.

    PMID: 2473841BACKGROUND

  • 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. doi: 10.1086/315016.

    PMID: 10479160BACKGROUND

  • 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. doi: 10.1016/0140-6736(90)92827-5.

    PMID: 1978068BACKGROUND

  • 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. doi: 10.1086/315078.

    PMID: 10515846BACKGROUND

  • 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. doi: 10.1038/35016636. No abstract available.

    PMID: 10890433BACKGROUND

  • 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.

    PMID: 12971464BACKGROUND

  • 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. doi: 10.1016/S0140-6736(98)08293-2.

    PMID: 10421302BACKGROUND

  • Schoonjans K, Auwerx J. Thiazolidinediones: an update. Lancet. 2000 Mar 18;355(9208):1008-10. doi: 10.1016/S0140-6736(00)90002-3.

    PMID: 10768450BACKGROUND

  • 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.

    PMID: 19673614DERIVED

Related Links

MeSH Terms

Conditions

Malaria, FalciparumMalaria

Interventions

Rosiglitazone

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ThiazolidinedionesThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Kevin C Kain, MD, FRCPC

    Faculty of Medicine, University of Toronto; McLaughlin-Rotman Center for Global Health, Toronto

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 6, 2005

First Posted

September 8, 2005

Study Start

December 1, 2004

Primary Completion

November 1, 2005

Study Completion

January 1, 2006

Last Updated

April 13, 2015

Record last verified: 2015-04

Locations

TH(1)