Ocular Changes After Ivermectin - (DOLF IVM/Oncho)

Microfilarial Clearance From the Eye and Ocular Changes Associated With Ivermectin Treatment in Individuals With Onchocerciasis

The DOLF Ocular Changes after Ivermectin study will investigate the kinetics of O. volvulus microfilaria (Mf) in the eye following treatment with ivermectin. The primary objective is to determine the proportion of participants with complete Mf clearance from the eye at 3 and 6 months following treatment with ivermectin (IVM).

Study Overview

• Status: Completed
• Conditions: Onchocerciasis
• Intervention / Treatment: Drug: Ivermectin 3Mg Tab

Detailed Description

This study will examine the kinetics of Mf clearance in the eye following ivermectin treatment. Previous studies have been unable to fully assess clearance Mf from the posterior chamber of the eye. This study will be the first to use optical coherence tomography (OCT) in patients with onchocerciasis to document parasites and pathology in the anterior and posterior chambers of the eye, and assess ocular changes following standard ivermectin treatment.

This will be a biomedical prospective cohort study.

The cohort will be stratified based on Mf levels to achieve approximately the following distribution of individuals with roughly one-third of participants in each group.

1. Individuals with positive skin snip Mf density of ≥ 1 Mf/mg), but no observable Mf in eyes using slit lamp and indirect ophthalmoscopy
2. Individuals with positive skin snip Mf density of ≥ 1 Mf/mg and 1-10 Mf in either eye at baseline (based on the highest number counted in either eye)
3. Individuals with positive skin snip Mf density of ≥ 1 Mf/mg and >10 Mf in either eye at baseline.

All participants recruited into the study will be treated with a single dose of ivermectin (150 ug/kg) by mouth under direct observation. This is the standard of care for treatment with onchocerciasis.

Participants will be evaluated following treatment with detailed parasitological and ocular examinations 7 days, 3 months and 6 months after treatment.

• Study Type: Interventional
• Enrollment (Actual): 231
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ghana
  • Hohoe, Ghana
    • University of Health and Allied Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have at least 1 palpable subcutaneous nodule (onchocercoma) and ≥ 1 Mf/mg of skin (by skin snip)

Exclusion Criteria:

• Pregnancy and breastfeeding mothers within 1 month of giving birth
• Have base line eye diseases including glaucoma, uveitis, severe keratitis, and/or cataracts that interfere with visualization of the posterior segment of the eye.
• Prior allergic / hypersensitivity reactions or intolerance to ivermectin
• Treatment with ivermectin in the past 6 (six) months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ivermectin; Single dose directly observed treatment with Ivermectin 3Mg Tab (150 ug/kg) delivered orally.	Drug: Ivermectin 3Mg Tab; ivermectin tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with complete microfilaria clearance from the eye at 3 months	Microfilaria in the anterior chamber of the eye will be counted during slit lamp examination at time of assessment. Participants without Mf in the eye will be considered clear of infection in the eye.	3 months following treatment
Number of participants with complete microfilaria clearance from the eye at 6 months	Microfilaria in the anterior chamber of the eye will be counted during slit lamp examination at time of assessment. Participants without Mf in the eye will be considered clear of infection in the eye.	6 months following treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change from baseline in the number of microfilaria detected in the skin at 3 months	Microfilaria (Mf) in the skin will be detected by skin snip microscopy. Up to four (4) skin snips using a corneoscleral punch will be weighed on an analytical balance and incubated for at least 8 hours in isotonic saline in a well of a flat-bottomed microtitre plate at ambient temperature. The Mf that have emerged will be counted using a microscope. Mf number and skin snip weight will be recorded. The mean skin microfilarial density will be calculated and recorded as mf/mg.	baseline, and 3 months following treatment
The change from baseline in the number of microfilaria detected in the skin at 6 months	Microfilaria (Mf) in the skin will be detected by skin snip microscopy. Up to four (4) skin snips using a corneoscleral punch will be weighed on an analytical balance and incubated for at least 8 hours in isotonic saline in a well of a flat-bottomed microtitre plate at ambient temperature. The Mf that have emerged will be counted using a microscope. Mf number and skin snip weight will be recorded. The mean skin microfilarial density will be calculated and recorded as mf/mg.	baseline, and 6 months following treatment
The change from baseline in the number of microfilaria detected in the eye at 3 months	Microfilaria in the anterior chamber of the eye will be counted during slit lamp examination at time of assessment.	baseline, 3 months following treatment
The change from baseline in the number of microfilaria detected in the eye at 6 months	Microfilaria in the anterior chamber of the eye will be counted during slit lamp examination at time of assessment.	baseline, 6 months following treatment
Number of participants with complete microfilaria clearance from the skin at 3 months	Microfilaria (Mf) in the skin will be detected by skin snip microscopy. Up to four (4) skin snips using a corneoscleral punch will be weighed on an analytical balance and incubated for at least 8 hours in isotonic saline in a well of a flat-bottomed microtitre plate at ambient temperature. The Mf that have emerged will be counted using a microscope. Mf number and skin snip weight will be recorded. Participants without Mf in the skin will be considered clear of infection in the skin.	3 months following treatment
Number of participants with complete microfilaria clearance from the skin at 6 months	Microfilaria (Mf) in the skin will be detected by skin snip microscopy. Up to four (4) skin snips using a corneoscleral punch will be weighed on an analytical balance and incubated for at least 8 hours in isotonic saline in a well of a flat-bottomed microtitre plate at ambient temperature. The Mf that have emerged will be counted using a microscope. Mf number and skin snip weight will be recorded. Participants without Mf in the skin will be considered clear of infection in the skin.	6 months following treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the utility of optical coherence tomography for evaluating the presence and clearance of Mf in the anterior and posterior segments of the eye.	Results from the optical coherence tomography (OCT) will be compared with slit lamp and other ocular examinations	baseline, 3 and 6 months following treatment
Evaluate ocular changes between baseline and 3 months following ivermectin treatment using OCT	Results from the optical coherence tomography (OCT) will be compared in participants pre and post treatment	baseline, and 3 months following treatment
Evaluate ocular changes between baseline and 6 months following ivermectin treatment using OCT	Results from the optical coherence tomography (OCT) will be compared in participants pre and post treatment	baseline, and 6 months following treatment

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Case Western Reserve University; University of Health and Allied Sciences
• Investigators: Principal Investigator: Gary Weil, MD, Washington University School of Medicine; Principal Investigator: Christopher King, MD PHD, Case Western Reserve University

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2018
• Primary Completion (Actual): August 23, 2019
• Study Completion (Actual): August 23, 2019

Study Registration Dates

• First Submitted: April 23, 2018
• First Submitted That Met QC Criteria: May 3, 2018
• First Posted (Actual): May 7, 2018

Study Record Updates

• Last Update Posted (Actual): December 31, 2020
• Last Update Submitted That Met QC Criteria: December 30, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: ophthalmology; mass drug administration
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Parasitic Diseases; Skin Diseases, Parasitic; Skin Diseases, Infectious; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Filariasis; Onchocerciasis; Anti-Infective Agents; Antiparasitic Agents; Ivermectin
• Other Study ID Numbers: 201804116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Datasets used for published results will be shared publically through a journal or other open source data repository so that the broader scientific community can access it. Only de-identified data will be shared publicly.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No