Lymphatic Filariasis (LF) in Ivory Coast

April 19, 2022 updated by: Christopher L. King, MD, PhD, University Hospitals Cleveland Medical Center

Alternative Chemotherapies for Lymphatic Filariasis (LF) Treatment and Elimination in Africa [Cote d'Ivoire]

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

189

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total clearance of Microfilariae
Time Frame: 36 months
The percentage of participants with total clearance of Microfilariae
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total clearance of MF at 24 months
Time Frame: 24 months
Percentage of subjects with total clearance of MF at 24 months
24 months
Percent MF reduction
Time Frame: 24 and 36 months
Percent MF reduction at 24 and 36 months compared to baseline level
24 and 36 months
Reduction in W. bancrofti antigen level
Time Frame: 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
12, 24 and 36 months
Alere Filariasis Test Strip negative
Time Frame: 12, 24 and 36 months
Percentage of subjects that become Alere Filariasis Test Strip negative at 12, 24 and 36 months
12, 24 and 36 months
reduction in viable worm nests
Time Frame: 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
12, 24, and 36 months
Diversity of parasites
Time Frame: 0 and 36 months
Diversity of parasites before and after treatment using genetic markers
0 and 36 months
type and level of parasite-specific host immune response
Time Frame: 0 and 36 months
Relation of type and level of parasite-specific host immune response with the initial and sustained clearance of parasites
0 and 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospitals Cleveland Medical Center

Collaborators

Washington University School of Medicine

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2015

Primary Completion (Actual)

September 1, 2018

Study Completion (Actual)

September 25, 2018

Study Registration Dates

First Submitted

November 22, 2016

First Submitted That Met QC Criteria

November 22, 2016

First Posted (Estimate)

November 28, 2016

Study Record Updates

Last Update Posted (Actual)

April 21, 2022

Last Update Submitted That Met QC Criteria

April 19, 2022

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-14-13

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Not personal identifying data but infection levels will be shared.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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