Antioxidant Micronutrients in Malaria

Malaria Clinical Trial

— AMM  

Official title:

Antioxidant Micronutrients in Malaria:a Randomised Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01152931
• Other study ID #: ULagosclinicaltrials
• Secondary ID: ULCT123456ULCT12
• Status: Completed
• Phase: Phase 3
• First received: June 28, 2010
• Last updated: May 30, 2012
• Start date: August 2010
• Est. completion date: December 2010

Study information

• Verified date: August 2010
• Source: University of Lagos, Nigeria
• Contact: n/a
• Is FDA regulated: No
• Health authority: Nigeria: The National Agency for Food and Drug Administration and Control
• Study type: Interventional

Clinical Trial 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.

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?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 5 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Amodiaquine + Artesunate
Intervention:the intervention in this group involves the use of standard antimalarial therapy for uncomplicated malaria based on WHO recommendation. artemisin based combination therapy will be used. amodiaquine will be administered via the oral route at a dose of 10mg/kg daily while artesunate will be administered orally at Artesunate 100mg stat, 50mg 8hrs later and 50mg bd x 3days
• Amodiaquine + Artesunate
Intervention:the intervention in this group involves the use of standard antimalarial therapy for uncomplicated malaria based on WHO recommendation. artemisinin based combination therapy will be used. amodiaquine will be administered via the oral route at a dose of 10mg/kg daily while artesunate will be administered orally at 100mg stat, 5omg 8hrs later and 50mg 12hrly for 3 days
• Lumefantrine + Artemether
Lumefantrine and artemether combination will be administered orally at a dose of 120/20mg daily for 3days

Dietary Supplement:
• Artesunate + vitamin A
Artesunate will be administered orally at a dose of 100mg stat then 50 mg 8hrs later and 50mg 12hrly for 3days. vitamin A will be administered orally at a dose of 2000IU daily for 3 days
• Artesunate + vitamin E
Artesunate will be administered orally at 100mg stat, then 50mg 8hrs after and 50mg 12hrly for 3 days. Vitamin E will be administered orally at 100mg dly for 3 days.
• Artesunate + Zinc
Artesunate will be administered orally at a dose of 100mg stat then 50mg 8hrs after and 50mg 12mg 12hrly for 3 days. Zinc gluconate will be administered orally at a dose of 50mg dly for 4 days
• Artesunate + selenium
Artesunate will be administered orally at 100mg stat and 8hrs later 50mg. then 50mg 12hrly for 3 days. selenium will be administered orally at a dose of 100ug dly for 4 days
• Amodiaquine + vitamin A
Amodiaquine will be administered orally at a dose of 10mg/kg dly for 3days. Vitamin A will be administered orally dly at a dose of 2000IU for 4 days
• Amodiaquine + Vitamin E
Amodiaquine will be administered orally at a dose of 10mg/kg dly for 3days. vitamin E will be administered orally at a dose 100mg daily for 4 days
• Amodiaquine + Zinc
Amodiaquine will be administered orally at a dose of 10mg/kg dly for 3days. Zinc gluconate will be administered orally at a dose of 50mg dly for 4 days.
• Amodiaquine + Selenium
Amodiaquine will be administered orally at a dose of 10mg/kg daily for 3days. Selenium will be administered orally at a dose of 100ug daily for 4 days if > 1year. 50ug daily for 4 days if < 1 year.
• Artesunate + vitamin A + vitamin E
Tab Artesunate 50mg orally daily for 4 days. Vitamin A, 5000IU orally daily for 4days if < 1 year. 10,000 IU orally daily for 4 days if > 1 year.
• 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.
• Artesunate + Vitamin A + Selenium
Tab 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.
• 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.
• Artesunate + Vitamin E + Zinc
Tab Artesunate administered orally at 50 mg daily for 4 days. Vitamin E 100 mg orally daily for 4 days. Tab Zinc 50 mg orally daily for 4 days if < 1 year. 25 mg orally daily for 4 days if > 1 year.

Locations

Country	Name	City	State
Nigeria	Central Primary Health Centre, Ukpenu, Road, Ekpoma.	Ekpoma	Edo State
Nigeria	Faithdome Medical Centre, Ekpoma.	Ekpoma	Esan West, Edo State

Sponsors (1)

Lead Sponsor	Collaborator
University of Lagos, Nigeria

Country where clinical trial is conducted

Nigeria, 

References & Publications (1)

Müller O, Becher H, van Zweeden AB, Ye Y, Diallo DA, Konate AT, Gbangou A, Kouyate B, Garenne M. Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomised double blind placebo controlled trial. BMJ. 2001 Jun 30;322(7302):1567. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	7-day cure rate	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	4 weeks	No
Secondary	28-day cure rate.	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).	4 weeks	No