- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00130065
The Effect of Folic Acid on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya
The Effect of Folic Acid Supplementation on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
In malaria endemic areas in sub-Saharan Africa, pregnant women, especially primi- and secundi-gravidae, are more likely to have placental and peripheral parasitemia with Plasmodium falciparum than non-pregnant women. Adverse consequences of malaria in pregnancy include maternal anemia, and low birth weight of the new born. Low birth weight is known to be the most important risk factor for infant mortality.
Intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) during pregnancy can mitigate the adverse effects of malaria in pregnancy and is the current standard of care in areas of high malaria transmission in sub-Saharan Africa, as recommended by the World Health Organization.
SP acts by inhibiting parasite enzymes in the metabolism of folic acid. However, in vitro studies indicate that folic acid can antagonize the antimalarial parasite activity of SP. Furthermore, in one West African study, supplementary folic acid compromised the antimalarial efficacy of SP in children with acute malaria aged 6 months to 12 years.
Folic acid requirements are increased during pregnancy, and supplementation with folic acid in pregnancy is recommended. Although in most countries a daily supplementation of 400 to 600 micrograms is considered sufficient, for logistical reasons the daily recommended dose in Kenya is 5 mg of folic acid during pregnancy. It is unknown whether folic acid supplementation might compromise the efficacy of IPT with SP in pregnant women living in malaria endemic areas.
Several studies have shown that HIV-seropositive pregnant women have a higher risk of malaria than HIV-seronegative pregnant women. In addition, HIV-infected women are more likely to be anemic compared with HIV-uninfected women. A few studies have also shown that HIV-seropositive women do not appear to respond as well to IPT with SP compared to HIV-seronegative pregnant women.
In a recent study in pregnant women in Zimbabwe, HIV-infection was a negative predictor of serum folate, and the authors suggested this may be because of reduced intake and absorption, and increased catabolism in HIV-infected pregnant women. Because HIV-seropositive women as a group may have a different folic acid status (and a potential different reaction to folic acid supplementation) than HIV-seronegative women, it is important to assess HIV-status in study participants. It is also important to confirm that no difference exists between HIV-seropositive and HIV-seronegative women in efficacy of SP for clearance of peripheral parasitemia.
Comparison: Parasitemic pregnant women are randomized to receive either SP with folic acid 5 mg, or SP with folic acid 0.4 mg, or SP and placebo. The placebo and the folic acid 0.4 mg are given for two weeks, and then are replaced by folic acid 5 mg.
Study Type
Enrollment
Phase
- Phase 4
Contacts and Locations
Study Locations
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Kisumu, Kenya
- CDC/Kenya Medical Research Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Parasitemia with a parasite density of ≥ 500 parasites/microliter
- Gestational age > 16 weeks and < 35 weeks
- Willingness to provide blood samples and participate in HIV counseling and testing
- Available for follow up for the entire study period
- Hemoglobin > 7 g/dl
- Age 15-45 years
Exclusion Criteria:
- Use of folate in the last 4 weeks
- Gestational age <16 weeks or >35 weeks
- History of an allergy to sulfonamides or other unknown drugs
- Intake of sulfa-containing drugs or 4-aminoquinolones in the previous month
- A urine test positive for sulfa-compounds
- Sickle cell disease
- Concomitant diseases needing treatment with co-trimoxazole or other sulfa-containing drug
- Hemoglobin < 7 g/dl
- Severe malaria or any other serious medical condition requiring hospitalization and/or additional treatment. Clinical danger signs of severe malaria include prostration, impaired consciousness, respiratory distress, multiple convulsions, circulatory collapse, pulmonary oedema, abnormal bleeding, jaundice, and hemoglobinuria. Laboratory signs of severe malaria include severe anemia (hemoglobin < 7 g/dl), hypoglycemia, acidosis, hyperlactataemia, hyperparasitaemia (a parasitemia > 100,000 parasites/µl), and renal impairment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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Hemoglobin level
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Peripheral parasitemia
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Secondary Outcome Measures
Outcome Measure |
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Effect of HIV serostatus on drug efficacy
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Collaborators and Investigators
Investigators
- Principal Investigator: Annemieke Van Eijk, M.D., Ph.D., Centers for Disease Control and Prevention, Kenya Medical Research Institiute
- Principal Investigator: Monica Parise, M.D., Centers for Disease Control and Prevention
- Principal Investigator: Laurence Slutsker, M.D., Centers for Disease Control and Prevention, Kenya Medical Research Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Vector Borne Diseases
- Parasitic Diseases
- Protozoan Infections
- Malaria
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Micronutrients
- Vitamins
- Antiprotozoal Agents
- Antiparasitic Agents
- Vitamin B Complex
- Hematinics
- Antimalarials
- Folic Acid Antagonists
- Anti-Infective Agents, Urinary
- Renal Agents
- Folic Acid
- Pyrimethamine
- Sulfadoxine
- Fanasil, pyrimethamine drug combination
Other Study ID Numbers
- CDC-NCID-3683
- UR6-CCU018970
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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