Age of Exposure and Immunity to Malaria in Infants
This study has been completed.
Sponsor:
Hospital Clinic of Barcelona
Collaborator:
European Commission
Information provided by:
Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:
NCT00231452
First received: September 30, 2005
Last updated: October 27, 2011
Last verified: October 2011
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Malaria |
Drug: Sulfadoxine-pyrimethamine (SP) + Artesunate (AS) |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) |
| Official Title: | Age of Exposure and Immunity to Malaria in Infants |
Resource links provided by NLM:
MedlinePlus related topics:
Malaria
Drug Information available for:
Pyrimethamine
U.S. FDA Resources
Further study details as provided by Hospital Clinic of Barcelona:
Primary Outcome Measures:
- (Clinical) Time to first or only episode of clinical malaria in the second year of life detected by passive case detection [ Time Frame: from 12 to 24 months of age ] [ Designated as safety issue: Yes ]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.
Secondary Outcome Measures:
- (Clinical) Time to first or only episode of malaria (using other case definitions), anaemia and other clinical endpoints. [ Time Frame: 12 to 24 months of age ] [ Designated as safety issue: Yes ]Global comparison between the 3 study groups of the time to first or only episode of clinical malaria (according to the secondary case definitions) in the second year of follow up detected by passive case detection. Other endpoints include multiple episodes of malaria, time to first or only episode of anaemia, total hospital visits and prevalence of parasitaemia and anaemia at different time points. In addition, pairwise comparisons of the 3 groups are also presented.
- Oxidative stress markers [ Time Frame: multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age) ] [ Designated as safety issue: No ]Quantification of the antioxidant/pro-oxidant status over the first two years of life in relation to age of first exposure to infection.
- Humoral and cellular immune responses [ Time Frame: multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age) ] [ Designated as safety issue: No ]Quantification of antibody and cytokine responses to P. falciparum protein antigens and toxins over the first two years of life in relation to age of first exposure to infection
- Host genetics [ Time Frame: 2.5 months of age ] [ Designated as safety issue: No ]Analysis of haematological genetic factors, polymorphisms in genes involved in inflammatory or immunological responses to malaria and polymorphisms in genes involved in the Th1/Th2 immunological pathway.
| Enrollment: | 349 |
| Study Start Date: | September 2005 |
| Study Completion Date: | March 2009 |
| Primary Completion Date: | March 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Late exposure group
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)
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.
|
|
Experimental: Early exposure group
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)
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.
|
|
Placebo Comparator: Control group
Participants received monthly placebo from 2.5 to 9.5 months of age.
|
Drug: Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)
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.
|
Eligibility| Ages Eligible for Study: | up to 1 Week |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Criteria
Inclusion Criteria:
Inclusion criteria for pregnant women:
- 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.
Inclusion criteria for newborn infants:
- Healthy infants, weighing >= 2 kg and having an alive mother.
Exclusion Criteria:
Exclusion criteria for pregnant women:
- 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).
Exclusion criteria for newborn infants:
- Any obvious congenital malformation;
- Any signs of cerebral asphyxia;
- Any obvious neonatal infection;
- Same gender Twins;
- Low birth weight (<2 kg).
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00231452
Locations
| Mozambique | |
| Centro de Investigaçao em Saude da Manhiça | |
| Manhiça, Maputo, Mozambique, 1929 | |
Sponsors and Collaborators
Hospital Clinic of Barcelona
European Commission
Investigators
| Principal Investigator: | 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 |
More Information
Additional Information:
No publications provided by Hospital Clinic of Barcelona
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| ClinicalTrials.gov Identifier: | NCT00231452 History of Changes |
| Other Study ID Numbers: | AgeMal |
| Study First Received: | September 30, 2005 |
| Last Updated: | October 27, 2011 |
| Health Authority: | Mozambique: Ministry of Health (MISAU) |
Keywords provided by Hospital Clinic of Barcelona:
|
natural acquired immunity, clinical malaria, P. falciparum, age, |
exposure, neonatal immunology, infants |
Additional relevant MeSH terms:
|
Malaria Protozoan Infections Parasitic Diseases Pyrimethamine Sulfadoxine Artesunate Sulfadoxine-pyrimethamine Antimalarials Antiprotozoal Agents Antiparasitic Agents |
Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Folic Acid Antagonists Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Infective Agents, Urinary Renal Agents Amebicides |
ClinicalTrials.gov processed this record on June 17, 2013