Ignite Creation Date:
2024-05-05 @ 5:22 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00440752
Status:
COMPLETED
Last Update Posted:
2008-03-26
First Post:
2007-02-26
Brief Title:
The Impact of Artemether-Lumefantrine on Genes Associated With Antimalarial Resistance
Sponsor:
Tropical Medicine Research Institute
Organization:
Tropical Medicine Research Institute
Study Overview
Official Title:
The Impact of Artemether-Lumefantrine on Genes Associated With Antimalarial Resistance in an Area of Seasonal Transmission
Status:
COMPLETED
Status Verified Date:
2007-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The newly introduced antimalarial drug artemether-lumefantrine is currently recommended as second line antimalarial in Sudan Recurrent infection after treatment with this drug has been associated with selection of certain genes in the malaria parasite However there is no information on this association in SudanThis study is going to look into the genetics of resistance to artemether-lumefantrine
Detailed Description:
In Sudan the current treatment protocol includes two artemisinin combinations ACT artesunate sulphadoxinepyrimethamine ASSP as first line and artemether-lumefantrine AL as second line This protocol has been implemented in 2004 since then various studies have reported the high efficacy of both combinations eg Adam et al 2005 Elamin et al 2005 Mohamed et al 2006
However there has been no report of the impact of these combinations on drug resistance markers in Sudan Data from other African countries has shown that AL selects for certain alleles in the pfmdr-1 gene Sisowath et al 2005 Dokomajilar et al 2006 Humphreys et al 2007 but the impact on the prevalence of different pfcrt and pfmdr-1alleles remains unclear It is essential to monitor ACT efficacy in addition to identify molecular markers that are associated with response to different drugs to facilitate epidemiological surveys for evidence based decision making Recent work in The Gambia suggests that transmission-related endpoints such as emergence of gametocytes after treatment may be better indicators of emerging drug resistance Hallett et al 2006
The aim of the proposed study is to examine the impact of treatment with artemether-lumefantrine AL on alleles of pfcrt and pfmdr-1 in P falciparum isolates in an area of marked seasonal transmission in eastern Sudan Most studies of resistance markers measure marker prevalence by DNA amplification but we will also investigate gene expression using quantitative amplification of mRNA encoding pfcrt and pfmdr-1 The impact of genotype and gene expression levels on treatment outcome and on the emergence and density of peripheral gametocytes will be examined
However there has been no report of the impact of these combinations on drug resistance markers in Sudan Data from other African countries has shown that AL selects for certain alleles in the pfmdr-1 gene Sisowath et al 2005 Dokomajilar et al 2006 Humphreys et al 2007 but the impact on the prevalence of different pfcrt and pfmdr-1alleles remains unclear It is essential to monitor ACT efficacy in addition to identify molecular markers that are associated with response to different drugs to facilitate epidemiological surveys for evidence based decision making Recent work in The Gambia suggests that transmission-related endpoints such as emergence of gametocytes after treatment may be better indicators of emerging drug resistance Hallett et al 2006
The aim of the proposed study is to examine the impact of treatment with artemether-lumefantrine AL on alleles of pfcrt and pfmdr-1 in P falciparum isolates in an area of marked seasonal transmission in eastern Sudan Most studies of resistance markers measure marker prevalence by DNA amplification but we will also investigate gene expression using quantitative amplification of mRNA encoding pfcrt and pfmdr-1 The impact of genotype and gene expression levels on treatment outcome and on the emergence and density of peripheral gametocytes will be examined
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None