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Efficacy of Ivermectin and Albendazole Against Onchocerciasis in the Volta Region, Ghana

Phase 3
Completed
Conditions
Onchocerciasis
Interventions
Drug: IVM
Drug: IVM plus ALB
Registration Number
NCT02078024
Lead Sponsor
University Hospitals Cleveland Medical Center
Brief Summary

We will examine whether a combination of Ivermectim (IVM) plus Albendazole (ALB) compared to IVM alone given annually, which is the current standard for mass drug administration (MDA), is more effective in sterilizing adult worms. We will also address whether IVM plus ALB given twice per year is superior to IVM given once per year or twice per year.

Detailed Description

We hypothesize that more effective combinations of dose schedules of existing antifilarial drugs for MDA against onchocerciasis could shorten the number of years needed to interrupt onchocerciasis transmission and eliminate this infectious disease in areas that previously had high disease rates. Improved treatments should also make it feasible to extend MDA into areas that are currently not being helped. These changes have the potential to completely change the game to make global elimination of onchocerciasis a feasible goal.

Participants will be randomized into 5 treatment arms with 75 subjects in each arm for a total of 375 and followed for 36 months after the initial treatment. The primary endpoint will be the percent fertile adult female worms in nodules removed 36 months after the initiation of treatment.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
375
Inclusion Criteria
  1. Men and women 18-60 years residing along the Kpassa in the Nkwanta North District of the Volta Region in Ghana
  2. Two or more assessable onchocercal nodules
  3. Skin microfilaria density ≥5mf/mg.
Exclusion Criteria
  1. Prior treatment with the antifilarial and/or anti-nematodal drugs diethylcarbamazine, suramin, ivermectin, albendazole, levamisole or >1week of treatment with doxycycline, within 12 months before planned test article administration.
  2. Pregnant or breastfeeding women.
  3. Low probability of residency in the area (based on subject's assessment) over the next 36 months.
  4. Permanent disability, serious medical illnesses such as a stroke, advanced heart disease, uncontrolled diabetes, emphysema, etc. that prevents or impedes study participation and/or comprehension
  5. Weight of <40kg suggesting malnourishment
  6. Hemoglobin levels <7 gm/dL
  7. aspartate aminotransferase, alanine aminotransferase, creatinine > 1.5 upper limit of normal.
  8. Significant glycosuria or proteinuria (2+ or 3+ protein or glucose).
  9. Known or suspected allergy to albendazole or ivermectin or other compounds related to these classes of medication.

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Annual IvermectinIVMIvermectin 200 µg/kg body weight given orally at 0, 12 and 24 months
Biannual IVM 200 µg/kgIVMIVM 200 µg/kg given 0, 6, 12, 18, and 24 months.
Biannual IVM 200 µg/kg plus ALB 800 mgIVM plus ALBIVM 200 µg/kg plus ALB 800 mg (regardless of weight) given at 0, 6, 12, 18, and 24 months.
Annual IVM 200 µg/kg plus ALB 800 mgIVM plus ALBIVM 200 µg/kg plus ALB 800 mg given at 0, 12 and 24 months; vitamin pills at given at 6 and 18 months.
IVM 200 µg/kg plus ALB 400 mgIVM plus ALBIVM 200 µg/kg plus ALB 400 mg given at 0, 6, 12, 18, and 24 months.
Primary Outcome Measures
NameTimeMethod
parasitologic efficacy36 months

To compare the parasitologic efficacy, as measured by percent fertile adult female worms in nodules at 36 months after administration of annual doses of oral ivermectin alone versus ivermectin plus albendazole given annually or biannually in the treatment of subjects infected with Onchocerca volvolus

Secondary Outcome Measures
NameTimeMethod
additional measures of parasitologic efficacy0, 6, 12, 18, 24 and 36 months

To compare additional measures of parasitologic efficacy of annual doses of oral ivermectin alone versus ivermectin plus albendazole given annually or biannually in the treatment of subjects infected with Onchocerca volvulus as measured by skin microfilaria levels at additional time points.

compare the percentage living versus dead female worms36 months

To compare the percentage living versus dead female worms in nodules at 36 months following initiation of therapy of annual doses of oral ivermectin alone versus ivermectin plus albendazole given annually or biannually in the treatment of subjects infected with Onchocerca volvulus.

assess different treatment regimens on Soil Transmitted Helminth infections0, 6, 12, 18, 24 and 36 months

To assess different treatment regimens on Soil Transmitted Helminth (STH) infections based on presence and intensity of ova in stools.

determine if IVM plus ALB enhances immunological reactions0, 6, 12, 18, 24 and 36 months

To determine if IVM plus ALB enhances immunological reactions to adult worms antigens, or release of circulating parasite antigens as potential biomarkers of drug efficacy.

determine if the host immune response facilitates killing or sterilizing adult worms and microfilariae0, 6, 12, 18, 24 and 36 months

To determine if the host immune response facilitates killing or sterilizing adult worms and microfilariae. This can be accomplished by examining immune biomarkers prior to and following treatment using stored whole blood, and serum/plasma samples.

compare the number of nodules with intact microfilaria36 months

To compare the number of nodules with intact microfilaria (Mf) at 36 months after administration annual doses of oral ivermectin alone versus ivermectin plus albendazole given annually or biannually in the treatment of subjects infected with Onchocerca volvulus.

Trial Locations

Locations (1)

Onchocerciasis Chemotherapy Research Centre, (OCRC) Municipal Hospital

🇬🇭

Hohoe, Ghana

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