Antioxidant Micronutrients in Malaria (AMM)

University of Lagos, Nigeria

Status and phase: Completed; Phase 3

Conditions: Malaria

Treatments: Dietary Supplement: Artesunate + vitamin A; Dietary Supplement: Artesunate + vitamin E; Dietary Supplement: Amodiaquine + Zinc; Dietary Supplement: Artesunate + Vitamin A + Selenium; Dietary Supplement: Artesunate + selenium; Dietary Supplement: Artesunate + Vitamin A + Zinc; Drug: Amodiaquine + Artesunate; Dietary Supplement: Amodiaquine + Selenium; Dietary Supplement: Amodiaquine + vitamin A; Dietary Supplement: Artesunate + Vitamin E + Selenium; Dietary Supplement: Artesunate + vitamin A + vitamin E; Drug: Lumefantrine + Artemether; Dietary Supplement: Artesunate + Vitamin E + Zinc; Dietary Supplement: Amodiaquine + Vitamin E; Dietary Supplement: Artesunate + Zinc

Study type: Interventional

Funder types: Other

Identifiers

NCT01152931

HCC8/T2A/443111 (Registry Identifier)

ULagosclinicaltrials

ULCT123456 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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?

Enrollment: 10 patients

Sex: All

Ages: 6 months to 5 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 15 patient groups

COHORT A= Amodiaquine + Artesunate

Active Comparator group

Description:

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

Treatment:

Drug: Amodiaquine + Artesunate

Drug: Amodiaquine + Artesunate

cohort B= Lumefantrine +Artemether

Active Comparator group

Description:

Artemether 20mg/Lumefantrine 120mg fixed combination administered daily for 3 days

Treatment:

Drug: Lumefantrine + Artemether

cohort C = Artesunate + vitamin A

Experimental group

Description:

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

Treatment:

Dietary Supplement: Artesunate + vitamin A

Artesunate, vitamin E oral administration

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Artesunate + vitamin E

cohort E will be given Artesunate and Zinc orally

Experimental group

Description:

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

Treatment:

Dietary Supplement: Artesunate + Zinc

cohort F= Artesunate and selenium will be given orally

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Artesunate + selenium

cohort G = Amodiaqiune and Vitamin A will be given orally

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Amodiaquine + vitamin A

cohort H = amodiaquine and vitamin E administerd orally

Experimental group

Description:

Amodiaquine 10mg/kg daily for 4 days + vitamin E 100 mg daily for 4 days

Treatment:

Dietary Supplement: Amodiaquine + Vitamin E

cohort I = Amodiaquine and Zinc will be given orally

Experimental group

Description:

Amodiaquine 10mg/kg daily for 4 days + zinc 50mg daily 4 days. if \< 1 year 25 mg daily for 4 days.

Treatment:

Dietary Supplement: Amodiaquine + Zinc

Cohort J = amodiaquine and selenium will be given orally

Experimental group

Description:

Amodiaquine 10mg/kg daily for 4 days + selenium 100ug daily for 4 days if \> 1 year. 50ug daily for 4 days if \< 1 year.

Treatment:

Dietary Supplement: Amodiaquine + Selenium

K= Artesunate+ vitamin A + vitamin E

Experimental group

Description:

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

Treatment:

Dietary Supplement: Artesunate + vitamin A + vitamin E

L = Artesunate+ Vitamin A + Zinc

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Artesunate + Vitamin A + Zinc

M = Artesunate+ Vitamin A + selenium

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Artesunate + Vitamin A + Selenium

N = Artesunate + Vitamin E + Zinc

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Artesunate + Vitamin E + Zinc

O = Artesunate+ Vitamin E + Selenium

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Artesunate + Vitamin E + Selenium