Antioxidant Micronutrients in Malaria (AMM)

• ClinicalTrials.gov Identifier: NCT01152931
• Recruitment Status: Completed
• First Posted: June 29, 2010
• Last Update Posted: May 31, 2012
• Sponsor: University of Lagos, Nigeria
• Information provided by: University of Lagos, Nigeria

Tracking Information

• First Submitted Date: June 28, 2010
• First Posted Date: June 29, 2010
• Last Update Posted Date: May 31, 2012
• Study Start Date: August 2010
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 28, 2010)

7-day cure rate [ Time Frame: 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 28, 2010)

28-day cure rate. [ Time Frame: 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).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Antioxidant Micronutrients in Malaria
• Official Title: Antioxidant Micronutrients in Malaria:a Randomised Clinical Trial
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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
• Drug: 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
• Drug: 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
• Dietary Supplement: 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.
• Dietary Supplement: 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
• Dietary Supplement: 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
• Dietary Supplement: 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
• Dietary Supplement: 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
• Dietary Supplement: 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.
• Dietary Supplement: 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.
• Dietary Supplement: 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.
• Dietary Supplement: 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.
• Dietary Supplement: 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.
• Dietary Supplement: 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.
• Dietary Supplement: 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.

Study Arms

• Active Comparator: COHORT A= 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
  Interventions:

  • Drug: Amodiaquine + Artesunate
  • Drug: Amodiaquine + Artesunate
• Active Comparator: cohort B= Lumefantrine +Artemether
  Artemether 20mg/Lumefantrine 120mg fixed combination administered daily for 3 days
  Intervention: Drug: Lumefantrine + Artemether
• Experimental: cohort C = 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
  Intervention: Dietary Supplement: Artesunate + vitamin A
• Experimental: Artesunate, vitamin E oral administration
  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.
  Intervention: Dietary Supplement: Artesunate + vitamin E
• Experimental: cohort E will be given Artesunate and Zinc orally
  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
  Intervention: Dietary Supplement: Artesunate + Zinc
• Experimental: cohort F= Artesunate and selenium will be given orally
  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.
  Intervention: Dietary Supplement: Artesunate + selenium
• Experimental: cohort G = Amodiaqiune and Vitamin A will be given orally
  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.
  Intervention: Dietary Supplement: Amodiaquine + vitamin A
• Experimental: cohort H = amodiaquine and vitamin E administerd orally
  Amodiaquine 10mg/kg daily for 4 days + vitamin E 100 mg daily for 4 days
  Intervention: Dietary Supplement: Amodiaquine + Vitamin E
• Experimental: cohort I = Amodiaquine and Zinc will be given orally
  Amodiaquine 10mg/kg daily for 4 days + zinc 50mg daily 4 days. if < 1 year 25 mg daily for 4 days.
  Intervention: Dietary Supplement: Amodiaquine + Zinc
• Experimental: Cohort J = amodiaquine and selenium will be given orally
  Amodiaquine 10mg/kg daily for 4 days + selenium 100ug daily for 4 days if > 1 year. 50ug daily for 4 days if < 1 year.
  Intervention: Dietary Supplement: Amodiaquine + Selenium
• Experimental: K= 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
  Intervention: Dietary Supplement: Artesunate + vitamin A + vitamin E
• Experimental: L = 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.
  Intervention: Dietary Supplement: Artesunate + Vitamin A + Zinc
• Experimental: M = 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.
  Intervention: Dietary Supplement: Artesunate + Vitamin A + Selenium
• Experimental: N = 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.
  Intervention: Dietary Supplement: Artesunate + Vitamin E + Zinc
• Experimental: O = 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.
  Intervention: Dietary Supplement: Artesunate + Vitamin E + Selenium

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 23, 2010): 10
• Original Estimated Enrollment (submitted: June 28, 2010): 14
• Actual Study Completion Date: December 2010
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 5 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Nigeria

Administrative Information

• NCT Number: NCT01152931
• Other Study ID Numbers: ULagosclinicaltrials; ULCT123456 ( Registry Identifier: ULCT123456 ); ULCT123456 ( Registry Identifier: Ministry of Health ); HCC8/T2A/443111 ( Registry Identifier: HCC8/T2A/443 )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Dr Iribhogbe Osede Ignis, Department of Pharmacology and Therapeutics, College of Medicine Ambrose Alli University, Ekpoma.
• Study Sponsor: University of Lagos, Nigeria
• Collaborators: Not Provided

Investigators

• Principal Investigator: Osede Ignis Iribhogbe, MB.BS, M.Sc; Department of Pharmacology and Therapeutics, College of Medicine, Ambrose Alli University, Ekpoma
• Study Director: Ibrahim Oreagba, B.Pharm, M.Sc, Ph.D; Deparment of Pharmacology, College of Medicine, University of Lagos, Nigeria
• Study Chair: Elizabeth O. Agbaje, B.Sc, M.Sc, MPhil, Ph.D; Department of Pharmacology, College of Medicine University of Lagos, Nigeria
• Study Director: Prof. Onyebiguwa Patrick NMORSI, PhD, MD; Dean, Faculty of Natural Sciences Ambrose Alli University Ekpoma

• PRS Account: University of Lagos, Nigeria
• Verification Date: August 2010