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Antioxidant Micronutrients in Malaria (AMM)

This study has been completed.
Sponsor:
Information provided by:
University of Lagos, Nigeria
ClinicalTrials.gov Identifier:
NCT01152931
First received: June 28, 2010
Last updated: May 30, 2012
Last verified: August 2010
History of Changes
  Purpose

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.


Condition Intervention Phase
Malaria
 Drug: Amodiaquine + Artesunate
Drug: Lumefantrine + Artemether
Dietary Supplement: Artesunate + vitamin A
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 + Selenium
Dietary Supplement: Artesunate + Vitamin E + Zinc
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Antioxidant Micronutrients in Malaria:a Randomised Clinical Trial

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Lagos, Nigeria:

Primary Outcome Measures:
  • 7-day cure rate [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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:
  • 28-day cure rate. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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).


Enrollment: 10
Study Start Date: August 2010
Study Completion Date: December 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
 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
Active Comparator: cohort B= Lumefantrine +Artemether
Artemether 20mg/Lumefantrine 120mg fixed combination administered daily for 3 days
 Drug: Lumefantrine + Artemether
Lumefantrine and artemether combination will be administered orally at a dose of 120/20mg daily for 3days
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
 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
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.
 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.
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
 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
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.
 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
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.
 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
Experimental: cohort H = amodiaquine and vitamin E administerd orally
Amodiaquine 10mg/kg daily for 4 days + vitamin E 100 mg daily 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
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.
 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.
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.
 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.
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
 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.
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.
 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.
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.
 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.
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.
 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.
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.
 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.

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?
  Eligibility

Ages Eligible for Study:   6 Months to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01152931

Locations
Nigeria
Central Primary Health Centre, Ukpenu, Road, Ekpoma.
Ekpoma, Edo State, Nigeria, +234
Faithdome Medical Centre, Ekpoma.
Ekpoma, Esan West, Edo State, Nigeria, +234
Sponsors and Collaborators
University of Lagos, Nigeria
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
  More Information

Additional Information:
chemoprophylactic effect of vitamin C in malaria  This link exits the ClinicalTrials.gov site

Publications:

Responsible Party: Dr Iribhogbe Osede Ignis, Department of Pharmacology and Therapeutics, College of Medicine Ambrose Alli University, Ekpoma.
ClinicalTrials.gov Identifier: NCT01152931     History of Changes
Other Study ID Numbers: ULagosclinicaltrials, ULCT123456, ULCT123456, HCC8/T2A/443111
Study First Received: June 28, 2010
Last Updated: May 30, 2012
Health Authority: Nigeria: The National Agency for Food and Drug Administration and Control

Keywords provided by University of Lagos, Nigeria:
Antioxidants
Micronutrients
Malaria
focus is to determine the effect of antioxidant micronutrients in malaria

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Amodiaquine
Artemether
Artesunate
Lumefantrine
Antioxidants
Selenium
Retinol palmitate
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Trace Elements
 Zinc
Vitamin A
Micronutrients
Vitamins
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Growth Substances
Anticarcinogenic Agents

ClinicalTrials.gov processed this record on May 16, 2013