Trial of Artemether-Lumefantrine Alone and in Combination With Ivermectin to Reduce Post-Treatment Malaria Transmission

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and impact of ivermectin, administered as single or repeated dose, in combination with artemether-lumefantrine in reducing the proportion of mosquitoes that survive and become infected after feeding on a blood meal from a malaria-infected individual.

Official Title
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A Double Blind Randomized Controlled Trial of Artemether-Lumefantrine Alone and in Combination With Ivermectin to Reduce Post-Treatment Malaria Transmission

Conditions
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Malaria

Intervention / Treatment
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* Drug: Artemether-lumefantrine combination
* Drug: Artemether-lumefantrine combination + single dose Ivermectin
* Drug: Artemether-lumefantrine combination + repeated dose Ivermectin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: asymptomatically infected individuals with any P. falciparum parasite density Exclusion Criteria: age < 15 years or > 25 years malaria parasite density ≥ 10,000 parasites/µL clinical symptoms indicating severe malaria axillary temperature ≥ 37.5°C Body Mass Index (BMI) below 18 or above 32 kg/m2 haemoglobin concentration below 11 g/dL taken ivermectin in the last three months Loa loa as assessed by questionnaire, clinical examination and parasitological assessments for women: pregnancy or lactation known hypersensitivity to AL or IVM history and/or symptoms indicating chronic illness current use of tuberculosis or anti-retroviral medication unable to give written informed consent unwillingness to participate in two membrane feeding assays travel history to Angola, Cameroon, Chad, Central African Republic, Congo, DR Congo, Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan. If a potential participant has ever visited one or more of these countries, he or she will not be eligible for enrolment. history of cardiovascular disease. taking drugs that are known to influence cardiac function and to prolong QTc interval, such as class IA and III: neuroleptics, antidepressant agents, certain antibiotics including some agents of the following classes - macrolides, fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics (terfenadine, astemizole) and cisapride. known disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia. taking drugs which may be metabolized by cytochrome enzyme CYP2D6 (e.g., flecainide, metoprolol, imipramine, amitriptyline, clomipramine).

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Artemether-Lumefantrine<br> | Drug: Artemether-lumefantrine combination<br>* Artemether-Lumefantrine (AL)combination; a placebo is given together with the first and fifth dose of AL<br>|
| Experimental: Artemether-Lumefantrine + single dose Ivermectin<br> | Drug: Artemether-lumefantrine combination + single dose Ivermectin<br>* Artemether-lumefantrine (AL) combination + Ivermectin (200ug/kg) given once together with the first dose of AL. A placebo is given together with the fifth dose of AL.<br>|
| Experimental: Artemether-Lumefantrine + repeated dose Ivermectin<br> | Drug: Artemether-lumefantrine combination + repeated dose Ivermectin<br>* Artemether-lumefantrine (AL) combination + Ivermectin (200ug/kg) given together with the first and fifth dose of AL.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | The number of adverse events; number of participants with abnormal haemoglobin, biochemistry or full blood count values | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mosquitocidal activity | Daily mortality rates of (malaria-infected) Anopheles gambiae s.s. and An. funestus mosquitoes after taking a blood meal 1, 3 or 7 days after initiation of treatment | feeding experiments performed up to 8 days after enrolment; survival of mosquitoes determined up to day 10 after feeding | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transmission, anopheles