The Impact of Artemether-Lumefantrine on Genes Associated With Antimalarial Resistance

This study has been completed.
Sponsor:
Collaborators:
London School of Hygiene and Tropical Medicine
World Health Organization
International Atomic Energy Agency
Information provided by:
Tropical Medicine Research Institute
ClinicalTrials.gov Identifier:
NCT00440752
First received: February 26, 2007
Last updated: March 25, 2008
Last verified: October 2007
  Purpose

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 Sudan.This study is going to look into the genetics of resistance to artemether-lumefantrine.


Condition
Falciparum Malaria
Antimalarials

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Impact of Artemether-Lumefantrine on Genes Associated With Antimalarial Resistance in an Area of Seasonal Transmission

Resource links provided by NLM:


Further study details as provided by Tropical Medicine Research Institute:

Primary Outcome Measures:
  • Levels of expression of pfcrt and pfmdr-1 alleles on day 0, 3, 7, 14, 21, 28 detected by real-time PCR. [ Time Frame: 2007 to 2009 ]

Secondary Outcome Measures:
  • Parasitological failure occurring at day 3, 7, 14, 21, 28 or any other day during this period. [ Time Frame: within 28 days of subject recruitment ]
  • Gametocyte development detected by reverse transcriptase PCR on day 0, 3, 14 and 28 [ Time Frame: 2008 to 2009 ]

Biospecimen Retention:   Samples With DNA

Blood spots on glass fibre membranes. 0.5ml of whole blood preserved in TRI reagent.


Enrollment: 100
Study Start Date: October 2006
Study Completion Date: December 2006
Groups/Cohorts
AL
Cohort of study participants receiving treatment with artemether-lumefantrine

Detailed Description:

In Sudan the current treatment protocol includes two artemisinin combinations (ACT); artesunate + sulphadoxine/pyrimethamine (AS/SP) 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 (e.g. 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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Criteria

Inclusion Criteria:

  • Mono-infection with P. falciparum by microscopy.
  • Initial parasite density of 1000 to 100,000 asexual parasites/µl.
  • Absence of general danger signs or other signs of severe and complicated falciparum malaria according to WHO definitions.
  • Informed consent provided by patient or parent/guardian.

Exclusion Criteria:

  • Pregnancy
  • Infection with mixed Plasmodium sp.
  • Signs of severe malaria or any danger signs
  • Refusal to provide consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00440752

Locations
Sudan
Tropical Medicine Research Institute
Khartoum, Sudan, 11111
Sponsors and Collaborators
Tropical Medicine Research Institute
London School of Hygiene and Tropical Medicine
World Health Organization
International Atomic Energy Agency
Investigators
Principal Investigator: Colin Sutherland, PhD. London School of Hygiene and Tropical Medicine
Study Chair: Badria B El-Sayed, PhD Tropical Medicine Research Institute
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00440752     History of Changes
Other Study ID Numbers: AL Oct-Dec/06-07
Study First Received: February 26, 2007
Last Updated: March 25, 2008
Health Authority: Sudan: Ministry of Health

Keywords provided by Tropical Medicine Research Institute:
Artemether-lumefantrine
Plasmodium falciparum
drug resistance genes

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Antimalarials
Artemether
Lumefantrine
Artemether-lumefantrine combination
Artemisinins
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Coccidiostats
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics

ClinicalTrials.gov processed this record on July 22, 2014