Ocular Changes After Ivermectin - (DOLF IVM/Oncho)

• ClinicalTrials.gov Identifier: NCT03517462
• Recruitment Status: Completed
• First Posted: May 7, 2018
• Last Update Posted: December 31, 2020
• Sponsor: Washington University School of Medicine
• Collaborators: Case Western Reserve University; University of Health and Allied Sciences
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Onchocerciasis	Drug: Ivermectin 3Mg Tab	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 231 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Participants are all given a standard treatment (ivermectin) for onchocerciasis.
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Microfilarial Clearance From the Eye and Ocular Changes Associated With Ivermectin Treatment in Individuals With Onchocerciasis
• Actual Study Start Date: August 6, 2018
• Actual Primary Completion Date: August 23, 2019
• Actual Study Completion Date: August 23, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of participants with complete microfilaria clearance from the eye at 3 months [ Time Frame: 3 months following treatment ]
   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.
2. Number of participants with complete microfilaria clearance from the eye at 6 months [ Time Frame: 6 months following treatment ]
   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.

Secondary Outcome Measures :

1. The change from baseline in the number of microfilaria detected in the skin at 3 months [ Time Frame: baseline, and 3 months following treatment ]
   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.
2. The change from baseline in the number of microfilaria detected in the skin at 6 months [ Time Frame: baseline, and 6 months following treatment ]
   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.
3. The change from baseline in the number of microfilaria detected in the eye at 3 months [ Time Frame: baseline, 3 months following treatment ]
   Microfilaria in the anterior chamber of the eye will be counted during slit lamp examination at time of assessment.
4. The change from baseline in the number of microfilaria detected in the eye at 6 months [ Time Frame: baseline, 6 months following treatment ]
   Microfilaria in the anterior chamber of the eye will be counted during slit lamp examination at time of assessment.
5. Number of participants with complete microfilaria clearance from the skin at 3 months [ Time Frame: 3 months following treatment ]
   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. Number of participants with complete microfilaria clearance from the skin at 6 months [ Time Frame: 6 months following treatment ]
   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.

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Ghana

University of Health and Allied Sciences

Hohoe, Ghana

Sponsors and Collaborators

Washington University School of Medicine

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

More Information

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• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03517462
• Other Study ID Numbers: 201804116
• First Posted: May 7, 2018
• Last Update Posted: December 31, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Washington University School of Medicine:

mass drug administration; ophthalmology

Additional relevant MeSH terms:

Onchocerciasis; Filariasis; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Skin Diseases; Ivermectin; Antiparasitic Agents; Anti-Infective Agents