Antioxidant Micronutrients in Malaria

Phase 3

Completed

• Conditions: Malaria
• Interventions: Drug: Lumefantrine + Artemether; Dietary Supplement: Artesunate + vitamin A; Drug: Amodiaquine + Artesunate; Dietary Supplement: Artesunate + vitamin E; Dietary Supplement: Artesunate + Zinc; Dietary Supplement: Artesunate + selenium; Dietary Supplement: Amodiaquine + vitamin A; Dietary Supplement: Amodiaquine + Vitamin E; Dietary Supplement: Amodiaquine + Zinc; Dietary Supplement: Amodiaquine + Selenium; Dietary Supplement: Artesunate + vitamin A + vitamin E; Dietary Supplement: Artesunate + Vitamin A + Zinc; Dietary Supplement: Artesunate + Vitamin A + Selenium; Dietary Supplement: Artesunate + Vitamin E + Zinc; Dietary Supplement: Artesunate + Vitamin E + Selenium

• Registration Number: NCT01152931
• Lead Sponsor: University of Lagos, Nigeria

Brief Summary

In the last decade, the prevalence of malaria has been escalating at an alarming rate, especially in Africa. An estimated 300 to 500 million cases each year cause 1.5 to 2.7 million deaths, more than 90% occur in children under 5 years of age in Africa (WHO 1995). Malaria is Africa's leading cause of under-five mortality (20%) and constitutes 10% of the continent's overall disease burden. It accounts for 40% of public health expenditure, 30-50% of inpatient admissions, and up to 50% of outpatient visits in areas with high malaria transmission. Antioxidant micronutrients have immunomodulatory role and may have suppressive activity.

Detailed Description

The pathogenesis of plasmodial infection hinges on intracellular invasion of host erythrocyte and hepatocyte with possible generation of free radicals that may contribute to cellular membrane damage. This will make uninfected erythrocyte and hepatocyte to be more susceptible to merozoite invasion. Zinc and Selenium has immunomodulatory properties. They enhance cell-mediated immune response in malaria infection. This may help to adequately suppress schizont maturation and inhibit the release of merozoites. However, it is possible that they have a direct chemosuppressive or blood schizonticidal effect. The following research questions emanated from this hypothesis;

1. Do the micronutrients in question have direct suppressive or schizonticidal effect?

2. Can they be used as short course therapy with standard antimalarials in uncomplicated malaria?

3. Is their effect enhanced when used in combination with each other or with standard antimalarials?

4. Do they have any prophylactic benefit?

5. Can their use alter the course of established malaria infection?

Study Timeline

• Study First Submitted: 2010-06-28
• Study First Submitted QC: 2010-06-28
• Study First Posted: 2010-06-29
• Status Verified: 2010-08
• Study Start: 2010-08
• Primary Completion: 2010-11
• Study Completion: 2010-12
• Last Update Submitted: 2012-05-30
• Last Update Posted: 2012-05-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• age of < 5 years
• asexual parasitemia of between 1,000 and 100,000/µl
• acute manifestation of malaria (e.g., history of fever in the preceding 24 hours or a temperature of >37.5°C at baseline)
• body weight between 5 and 30 kg
• ability to tolerate oral therapy
• informed consent by the legal representative of the subject (the parents, if possible), oral agreement of the child if appropriate
• resident in the study area for a duration of at least 4 weeks

Exclusion Criteria

• adequate antimalarial treatment within the previous 7 days

  • use of micronutrients in the last 2 weeks
  • antibiotic treatment for a concurrent infection
  • hemoglobin level of <7 g/dl
  • hematocrit of <25%
  • leukocyte count of >15,000/µl
  • mixed plasmodial infection
  • severe malaria, any other severe underlying disease
  • concomitant disease masking assessment of the treatment response
  • inflammatory bowel disease, and any other disease causing fever

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
cohort B= Lumefantrine +Artemether	Lumefantrine + Artemether	Artemether 20mg/Lumefantrine 120mg fixed combination administered daily for 3 days
cohort C = Artesunate + vitamin A	Artesunate + vitamin A	Artesunate 50mg daily for 4days. if \>6 months\< 1 year 4mg/kg daily for 4days + Vitamin A 5000IU daily for 4days if \< 1 year and 10,000IU daily for 4days if \> 1 year respectively
COHORT A= Amodiaquine + Artesunate	Amodiaquine + Artesunate	Amodiaquine will be administered orally at 10mg/kg daily for 3days. Artesunate 50mg will be administered orally daily for 3days.For subjects \>6months\< 1 years 4mg/kg daily for 3 days
Artesunate, vitamin E oral administration	Artesunate + vitamin E	Artesunate 50mg daily for 4 days.if \>6 months\< 1 year 4mg/kg daily for 4 days + vitamin E 100mg daily administered orally to the experimental group 4 days.
cohort E will be given Artesunate and Zinc orally	Artesunate + Zinc	cohort E will be given Artesunate 50mg daily for 4 days. if \> 6 months\< 1 year 4mg/kg daily for 4 days + zinc gluconate 50mg orally daily for 4 days. if \< 1 year 25 mg daily for 4 days
cohort F= Artesunate and selenium will be given orally	Artesunate + selenium	Artesunate 50mg daily for 4 days. if \> 6 months\< 1 year 4mg/kg daily for 4 days + selenium 100ug daily for 4 days. if \< 1 year 50ug daily for 4 days.
cohort G = Amodiaqiune and Vitamin A will be given orally	Amodiaquine + vitamin A	Amodiaquine 10mg/kg daily for 3 days + vitamin A 5000iu daily for 4 days if \< 1 year. 10,000 IU daily for 4 days if \> 1 year.
cohort H = amodiaquine and vitamin E administerd orally	Amodiaquine + Vitamin E	Amodiaquine 10mg/kg daily for 4 days + vitamin E 100 mg daily for 4 days
cohort I = Amodiaquine and Zinc will be given orally	Amodiaquine + Zinc	Amodiaquine 10mg/kg daily for 4 days + zinc 50mg daily 4 days. if \< 1 year 25 mg daily for 4 days.
Cohort J = amodiaquine and selenium will be given orally	Amodiaquine + Selenium	Amodiaquine 10mg/kg daily for 4 days + selenium 100ug daily for 4 days if \> 1 year. 50ug daily for 4 days if \< 1 year.
K= Artesunate+ vitamin A + vitamin E	Artesunate + vitamin A + vitamin E	Tab Artesunate 50mg orally dly x 4 days + Vitamin A, 5000IU orally, dly x 4 days if ≤ 1yr. 10,000IU orally dly x 4days if \> 1 yr + vitamin E 100 mg orally dly for 4 days
L = Artesunate+ Vitamin A + Zinc	Artesunate + Vitamin A + Zinc	Tab Artesunate 50 mg daily for 4 days. Vitamin A 5OOOIU daily for 4 days if \< 1 year. 10,000IU daily for 4 days if \> 1 year. All administered orally.
M = Artesunate+ Vitamin A + selenium	Artesunate + Vitamin A + Selenium	Artesunate 50 mg orally, daily for 4 days. Vitamin A 5000IU orally daily for 4 days if \< 1 year. 10,000IU orally daily for 4 days if \> 1 year.
N = Artesunate + Vitamin E + Zinc	Artesunate + Vitamin E + Zinc	Artesunate 50mg daily for 4 days. vitamin E 100mg daily for 4 days. Zinc 50 mg daily for 4 days if \> 1 year. 25 mg daily for 4 days if \< 1 year.
O = Artesunate+ Vitamin E + Selenium	Artesunate + Vitamin E + Selenium	Tab Artesunate 50 mg orally daily for 4 days. Vitamin E 100 mg orally daily for 4 days. Tab selenium 100 ug orally daily for 4 days if \> 1 year. 50 ug orally daily for 4 days if \< 1 year.

Primary Outcome Measures

Name	Time	Method
7-day cure rate	4 weeks	7-day Cure rate will be defined as initial and sustained parasite and symptom clearance with no increase in asexual parasitemia 48 h after the initiation of treatment and the absence of microscopically detected asexual parasitemia within 120 h of the commencement of treatment until day 7

Secondary Outcome Measures

Name	Time	Method
28-day cure rate.	4 weeks	the number of patients with clinical and parasitological cure by day 28 divided by the total number of patients who could be evaluated (per protocol population).

Trial Locations

Locations (2)

Central Primary Health Centre, Ukpenu, Road, Ekpoma.; 🇳🇬 Ekpoma, Edo State, Nigeria

Faithdome Medical Centre, Ekpoma.; 🇳🇬 Ekpoma, Esan West, Edo State, Nigeria