NCT00231452

Brief Summary

The overall objective is to evaluate the effect of exposure to Plasmodium (P.) falciparum erythrocytic stage antigens during different periods of infancy on the development of naturally acquired immunity (NAI). Hypothesis: Exposure to P. falciparum prior to 5 months of age does not result in the development of NAI, while exposure to P. falciparum after 5 months of age leads to the development of NAI. The risks of clinical malaria and anaemia during the second year of life will be compared between cohorts, as well as their correlations with the type and quality of immune responses (antibodies to several P. falciparum antigens, cytokines), oxidative stress markers and host genetic factors. These results should shed light on the determinants of the development of anti-P. falciparum responses early in life and the potential constraints to early life immunisation.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
349

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Sep 2005

Longer than P75 for not_applicable

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

September 1, 2005

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

September 30, 2005

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 4, 2005

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2009

Completed
Last Updated

October 28, 2011

Status Verified

October 1, 2011

Enrollment Period

3.5 years

First QC Date

September 30, 2005

Last Update Submit

October 27, 2011

Conditions

Malaria

Keywords

natural acquired immunity,clinical malaria,P. falciparum,age,exposure,neonatal immunology,infants

Outcome Measures

Primary Outcomes (1)

  • (Clinical) Time to first or only episode of clinical malaria in the second year of life detected by passive case detection

    Global comparison between the 3 groups of the time to first or only episode of clinical malaria (according to the primary case definition) in the second year of follow up detected by passive case detection in the According-To-Protocol cohort. In addition, pairwise comparisons of the 3 groups are also presented.

    from 12 to 24 months of age

Secondary Outcomes (4)

  • (Clinical) Time to first or only episode of malaria (using other case definitions), anaemia and other clinical endpoints.

    12 to 24 months of age

  • Oxidative stress markers

    multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age)

  • Humoral and cellular immune responses

    multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age)

  • Host genetics

    2.5 months of age

Study Arms (3)

Late exposure group

EXPERIMENTAL

Participants received monthly Sulfadoxine-Pyrimethamine (SP) plus Artesunate (AS) from 2.5-4.5 months of age and monthly placebo from 5.5-9.5 months of age.

Drug: Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)

Early exposure group

EXPERIMENTAL

Participants received monthly placebo from 2.5-4.5 months of age and monthly SP+AS from 5.5-9.5 months of age.

Drug: Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)

Control group

PLACEBO COMPARATOR

Participants received monthly placebo from 2.5 to 9.5 months of age.

Drug: Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)

Interventions

Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)DRUG

Monthly chemoprophylaxis with SP (Fansidar® 500/25 mg) plus Artesunate (AS, Arsumax® 50 mg) or placebo (provided by Roche and Sanofi-Aventis) was administered according to the following age-based dosing schedule: ½ tablet of SP or placebo and ½ tablet of AS or placebo on the first day and ½ tablet of AS or placebo on the second and third days.

Control groupEarly exposure groupLate exposure group

Eligibility Criteria

AgeUp to 1 Week
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Healthy HIV-negative pregnant females less than 50 years of age who attend the voluntary counseling and testing (VCT) center at the Maragra or Manhiça antenatal clinic,
  • Permanent residents of the Manhiça area and expecting to be living in the area with their infant for at least 2 years.
  • Healthy infants, weighing \>= 2 kg and having an alive mother.

You may not qualify if:

  • Plan to leave the area in less than 2 years from the start of the study;
  • Women not willing to get tested for HIV infection at the VCT center;
  • Test positive for HIV;
  • Not willing to provide informed consent;
  • Cannot understand either Portuguese or Changana (consent forms are written in these languages).
  • Any obvious congenital malformation;
  • Any signs of cerebral asphyxia;
  • Any obvious neonatal infection;
  • Same gender Twins;
  • Low birth weight (\<2 kg).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centro de Investigaçao em Saude da Manhiça

Manhiça, Maputo Province, 1929, Mozambique

Location

Related Publications (3)

  • Dobano C, Nhabomba AJ, Manaca MN, Berthoud T, Aguilar R, Quinto L, Barbosa A, Rodriguez MH, Jimenez A, Groves PL, Santano R, Bassat Q, Aponte JJ, Guinovart C, Doolan DL, Alonso PL. A Balanced Proinflammatory and Regulatory Cytokine Signature in Young African Children Is Associated With Lower Risk of Clinical Malaria. Clin Infect Dis. 2019 Aug 16;69(5):820-828. doi: 10.1093/cid/ciy934.

    PMID: 30380038DERIVED

  • Nhabomba AJ, Guinovart C, Jimenez A, Manaca MN, Quinto L, Cistero P, Aguilar R, Barbosa A, Rodriguez MH, Bassat Q, Aponte JJ, Mayor A, Chitnis CE, Alonso PL, Dobano C. Impact of age of first exposure to Plasmodium falciparum on antibody responses to malaria in children: a randomized, controlled trial in Mozambique. Malar J. 2014 Mar 27;13:121. doi: 10.1186/1475-2875-13-121.

    PMID: 24674654DERIVED

  • Guinovart C, Dobano C, Bassat Q, Nhabomba A, Quinto L, Manaca MN, Aguilar R, Rodriguez MH, Barbosa A, Aponte JJ, Mayor AG, Renom M, Moraleda C, Roberts DJ, Schwarzer E, Le Souef PN, Schofield L, Chitnis CE, Doolan DL, Alonso PL. The role of age and exposure to Plasmodium falciparum in the rate of acquisition of naturally acquired immunity: a randomized controlled trial. PLoS One. 2012;7(3):e32362. doi: 10.1371/journal.pone.0032362. Epub 2012 Mar 7.

    PMID: 22412865DERIVED

Related Links

MeSH Terms

Conditions

Malaria

Interventions

fanasil, pyrimethamine drug combinationArtesunate

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsSesquiterpenesTerpenesHydrocarbons

Study Officials

  • Pedro Alonso, MD, PhD

    Barcelona Center for International Health Research, Hospital Clinic/University of Barcelona

    PRINCIPAL INVESTIGATOR

  • Carlota Dobaño, PhD

    Barcelona Center for International Health Research, Hospital Clinic/University of Barcelona

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

September 30, 2005

First Posted

October 4, 2005

Study Start

September 1, 2005

Primary Completion

March 1, 2009

Study Completion

March 1, 2009

Last Updated

October 28, 2011

Record last verified: 2011-10

Locations

MO(1)