Lymphatic Filariasis (LF) in Ivory Coast

Sponsor
University Hospitals Cleveland Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT02974049
Collaborator
Washington University School of Medicine (Other)
189
1
4
44.8
4.2

Study Details

Study Description

Brief Summary

The recommended treatment for elimination of LF in sub-Saharan Africa is annual mass drug administration (MDA) with single dose Albendazole (ALB) plus Ivermectin (IVM) given for at least 5-7 years. However, in areas where LF is co-endemic with a related filarial parasite, Loa loa, co-infection with L. loa represents a serious barrier to LF elimination because IVM used in LF MDA can result in severe reactions and even death in individuals with high microfilaria (mf) levels of L. loa. Screening for heavy L. loa infection is problematic. To overcome this problem, monotherapy with ALB is possible, since this drug has little or no effect on circulating mf and thus would not cause adverse effects in people with heavy L. loa infections. Moreover ALB has been shown to have embryostatic or embryocidal effects in female adult worms resulting in decreased mf levels with time as natural attrition of circulating mf occurs. Thus this open-label, randomized clinical trial will examine treatment with ALB monotherapy administered twice per year over a period of 3 years with the primary endpoint being the proportion of individuals with total clearance of mf at 36 months and Alere antigen test negativity (a more sensitive circulating antigen test of filarial infection). Two of the treatment arms will include ALB at two different doses, 400mg or 800mg (fixed dose twice yearly) as compared to standard treatment of ALB (400 mg) plus IVM (150-200 µg/kg) administered annually. Observations from an ongoing clinical trial in Papua New Guinea suggest that a single dose of triple therapy with ALB + IVM + DEC may be highly effective in sterilizing adult female worms. Therefore to confirm and expand these important preliminary observations in a different population, a fourth arm will be included in the current clinical trial in which subjects will receive all three drugs. The clinical trial will be performed in a region of Cote d'Ivoire where onchocerciasis and loiasis are not endemic.

Condition or Disease Intervention/Treatment Phase
N/A

Detailed Description

Lymphatic filariasis (LF) is a deforming and disabling infectious disease that causes elephantiasis and genital deformity (especially hydroceles). The infection affects some 120 million people in 81 countries in tropical and subtropical regions with well over 1 billion people at risk of acquiring the disease. LF is caused by Wuchereria bancrofti and Brugia spp. (B. malayi and B. timori), nematode parasites that are transmitted by mosquitoes. The World Health Organization (WHO) developed a plan for LF elimination that is based on using novel approaches to rapidly map endemic areas and 4 to 6 annual rounds of MDA with antifilarial medication. A recent summary from WHO reported that more than 4 billion doses of MDA were distributed between 2000 and 2012. Thus, the Global Program to Eliminate Lymphatic Filariasis (GPELF) is the largest infectious disease intervention program attempted to date based on MDA (Ottesen, Hooper et al.

2008). MDA has worked better in some areas than others. There are a number of challenges faced by GPELF. These include (among others) inability to conduct MDA programs in areas of Africa where L. loa is coendemic because of the unacceptable risk of Serious Adverse Events (SAE's) with IVM in persons with heavy L. loa infections (Hoerauf, Pfarr et al. 2011), the limited macrofilaricidal activity of current MDA regimens (especially ALB + IVM) that necessitate repeated annual rounds of MDA (Geary and Mackenzie , Hoerauf, Pfarr et al. 2011), and the difficulty of achieving high compliance rates for MDA over a period of years (Hoerauf, Pfarr et al. 2011). It is clear that new (or reformulated) drugs and/or dosing schedules for LF MDA have the potential to greatly improve the number of countries that will successfully eliminate LF by the WHO target date of 2020. This is especially important for areas of Central and West Africa where MDA has not been implemented because of the possible co-infection with L. loa and logistical and financial challenges to delivering annual doses of IVM + ALB MDA to millions of individuals over multiple years.

Study Design

Study Type:
Interventional
Actual Enrollment :
189 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Alternative Chemotherapies for Lymphatic Filariasis (LF) Treatment and Elimination in Africa [Cote d'Ivoire]
Actual Study Start Date :
Jan 1, 2015
Actual Primary Completion Date :
Sep 1, 2018
Actual Study Completion Date :
Sep 25, 2018

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Standard Treatment

Albendazole 400 mg + Ivermectin 200 µg/kg body weight administered annually (at 0, 12 and 24 months)

Drug: Albendazole
Subjects in Arms 1, 2, and 4 will receive 400mg of Albendazole Subjects in Arm 3 will receive 800mg of Albendazole
Other Names:
  • ALB
  • Drug: Ivermectin
    Subjects in Arms 1 and 4 will receive 200mg/kg body weight
    Other Names:
  • IVM
  • Experimental: ALB 400 mg x2 per year

    Albendazole 400 mg given at 0, 6, 12, 18, 24 and 30 months

    Drug: Albendazole
    Subjects in Arms 1, 2, and 4 will receive 400mg of Albendazole Subjects in Arm 3 will receive 800mg of Albendazole
    Other Names:
  • ALB
  • Experimental: ALB 800 mg x2 per year

    Albendazole 800 mg given at 0, 6, 12, 18, 24 and 30 months

    Drug: Albendazole
    Subjects in Arms 1, 2, and 4 will receive 400mg of Albendazole Subjects in Arm 3 will receive 800mg of Albendazole
    Other Names:
  • ALB
  • Experimental: ALB 400mg + IVM 200mcg/kg + DEC 6mg/kg

    Albendazole 400 mg plus Ivermectin 200 µg/kg body weight plus Diethylcarbamazine 6 mg/kg body weight given one time only

    Drug: Albendazole
    Subjects in Arms 1, 2, and 4 will receive 400mg of Albendazole Subjects in Arm 3 will receive 800mg of Albendazole
    Other Names:
  • ALB
  • Drug: Ivermectin
    Subjects in Arms 1 and 4 will receive 200mg/kg body weight
    Other Names:
  • IVM
  • Drug: Diethylcarbamazine
    Participants in Arm 4 will receive 6mg/kg of Diethylcarbamazine per body weight
    Other Names:
  • DEC
  • Outcome Measures

    Primary Outcome Measures

    1. Total clearance of Microfilariae [36 months]

      The percentage of participants with total clearance of Microfilariae

    Secondary Outcome Measures

    1. Total clearance of MF at 24 months [24 months]

      Percentage of subjects with total clearance of MF at 24 months

    2. Percent MF reduction [24 and 36 months]

      Percent MF reduction at 24 and 36 months compared to baseline level

    3. Reduction in W. bancrofti antigen level [12, 24 and 36 months]

      Percent reduction in W. bancrofti antigen level measured by Og4C3 assay at 12, 24 and 36 months compared to baseline level

    4. Alere Filariasis Test Strip negative [12, 24 and 36 months]

      Percentage of subjects that become Alere Filariasis Test Strip negative at 12, 24 and 36 months

    5. reduction in viable worm nests [12, 24, and 36 months]

      Percent reduction in viable worm nests relative to baseline (time 0) based on follow up scrotal ultrasound examination performed at 12, 24 and 36 months

    6. Diversity of parasites [0 and 36 months]

      Diversity of parasites before and after treatment using genetic markers

    7. type and level of parasite-specific host immune response [0 and 36 months]

      Relation of type and level of parasite-specific host immune response with the initial and sustained clearance of parasites

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Women and men 18-70 years

    • ≥50 MF/mL based on Nuclepore filtration

    • Willing to give informed consent

    Exclusion Criteria:
    • Prior treatment for LF within last 5 years

    • Pregnancy (perform pregnancy test)

    • Hemoglobin <7 g/dL

    • Permanent disability, serious medical illness that prevents or impedes study participation and/or comprehension

    • AST/ALT and creatinine >1.5 upper limit of normal

    • Proteinuria or hematuria >3+

    • Skin snip positivity for O. volvulus MF

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Cote d'Ivoire Abidjan Côte D'Ivoire

    Sponsors and Collaborators

    • University Hospitals Cleveland Medical Center
    • Washington University School of Medicine

    Investigators

    • Principal Investigator: Christopher L King, MD PhD, Case Western Reserve University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Christopher L. King, MD, PhD, Professor of International Health, Medicine and Pathology, Case Western Reserve University
    ClinicalTrials.gov Identifier:
    NCT02974049
    Other Study ID Numbers:
    • 08-14-13
    First Posted:
    Nov 28, 2016
    Last Update Posted:
    Apr 21, 2022
    Last Verified:
    Apr 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Christopher L. King, MD, PhD, Professor of International Health, Medicine and Pathology, Case Western Reserve University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 21, 2022