PREVAIL VII: Persistence of Ebola Virus in Aqueous Humor and Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease

ID: NCT03309020
Status: Not yet recruiting
Phase: N/A
Start Date: March 01, 2018
First Submitted: October 12, 2017
Last Updated: February 23, 2018
Results: N/A
Sponsors & Collaborators: National Eye Institute (NEI)
Location: Liberia
Conditions: Cataract
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Study Description

Brief Summary

Objective: Zaire ebolavirus is a single-stranded RNA virus associated with high morbidity and mortality. The most recent epidemic of Ebola virus disease (EVD) in West Africa resulted in over 11,000 deaths and disabling sequelae among survivors, among which eye complications are highly represented. Chronic intraocular inflammation and viral persistence may result in posterior synechiae and cataract formation, resulting in loss of visual acuity and requiring surgical intervention to resolve. Approximately one out of ten Ebola survivors present with cataract, most of whom will require intraocular surgery during their lifetime, and many of whom require intervention in the near future to regain quality of life. For survivors who are blind from cataract, cataract extraction is necessary to restore visual function, allow reintegration into society and facilitate performance of activities of daily living.

However, surgical parameters among Ebola survivors are unknown, including whether Ebola viral RNA persists in aqueous humor, whether additional anti-inflammatory medication is needed, and the expected degree of improvement in visual function. Moreover, sites of viral persistence are unknown, and it is unclear if lens tissues removed during cataract surgery may harbor virus in Ebola-affected eyes. We propose following EVD survivors and control subjects undergoing cataract surgery to determine visual outcomes among Ebola survivors and explore detection of the presence of virus in lens tissues. The data will inform both future surgical intervention and aid in the understanding of the pathophysiology of Ebola-associated eye disease.

Study Population: Up to 60 Ebola survivors and up to 60 controls will be enrolled. The accrual ceiling is 120 participants.

Design: This is a prospective, natural history study to evaluate the persistence of Ebola viral RNA in the eyes of Ebola survivors and assess the response to cataract surgery in survivors as compared to controls. EVD survivors will first undergo assessment of aqueous humor for the presence of viral RNA. Survivors testing negative for viral RNA and control subjects will undergo clinically indicated cataract surgery. Subjects will be evaluated 1 day, 1 week, 1 month, and 3 months after surgery for safety and visual outcome assessments, and more often as clinically indicated.

Outcome Measures: The primary outcomes are: 1) the proportion of EVD survivors with evidence of persistence of Ebola viral RNA in ocular tissue and 2) the comparison of amount of intraocular inflammation, as measured by average grade of anterior chamber cell by SUN criteria, between EVD survivors and controls at 1 month and 3 months following cataract surgery. Secondary outcomes include: 1) the proportion of survivors with at least 20/40 best corrected visual acuity (BCVA) after cataract surgery, relative to controls; 2) significance of covariates, age and gender, in logistic regression assessment of viral persistence and cataract outcomes; 3) post-operative optical coherence tomography results in EVD survivors.

Detailed Description

Objective: Zaire ebolavirus is a single-stranded RNA virus associated with high morbidity and mortality. The most recent epidemic of Ebola virus disease (EVD) in West Africa resulted in over 11,000 deaths and disabling sequelae among survivors, among which eye complications are highly represented. Chronic intraocular inflammation and viral persistence may result in posterior synechiae and cataract formation, resulting in loss of visual acuity and requiring surgical intervention to resolve. Approximately one out of ten Ebola survivors present with cataract, most of whom will require intraocular surgery during their lifetime, and many of whom require intervention in the near future to regain quality of life. For survivors who are blind from cataract, cataract extraction is necessary to restore visual function, allow reintegration into society and facilitate performance of activities of daily living.

However, surgical parameters among Ebola survivors are unknown, including whether Ebola viral RNA persists in aqueous humor, whether additional anti-inflammatory medication is needed, and the expected degree of improvement in visual function. Moreover, sites of viral persistence are unknown, and it is unclear if lens tissues removed during cataract surgery may harbor virus in Ebola-affected eyes. We propose following EVD survivors and control subjects undergoing cataract surgery to determine visual outcomes among Ebola survivors and explore detection of the presence of virus in lens tissues. The data will inform both future surgical intervention and aid in the understanding of the pathophysiology of Ebola-associated eye disease.

Study Population: Up to 60 Ebola survivors and up to 60 controls will be enrolled. The accrual ceiling is 120 participants.

Design: This is a prospective, natural history study to evaluate the persistence of Ebola viral RNA in the eyes of Ebola survivors and assess the response to cataract surgery in survivors as compared to controls. EVD survivors will first undergo assessment of aqueous humor for the presence of viral RNA. Survivors testing negative for viral RNA and control subjects will undergo clinically indicated cataract surgery. Subjects will be evaluated 1 day, 1 week, 1 month, and 3 months after surgery for safety and visual outcome assessments, and more often as clinically indicated.

Outcome Measures: The primary outcomes are: 1) the proportion of EVD survivors with evidence of persistence of Ebola viral RNA in ocular tissue and 2) the comparison of amount of intraocular inflammation, as measured by average grade of anterior chamber cell by SUN criteria, between EVD survivors and controls at 1 month and 3 months following cataract surgery. Secondary outcomes include: 1) the proportion of survivors with at least 20/40 best corrected visual acuity (BCVA) after cataract surgery, relative to controls; 2) significance of covariates, age and gender, in logistic regression assessment of viral persistence and cataract outcomes; 3) post-operative optical coherence tomography results in EVD survivors.
Condition or disease Intervention/treatment Phase

Cataract

N/A

Tracking Information

First Submitted DateOctober 12, 2017
Last Update Posted DateFebruary 23, 2018
Anticipated Start DateMarch 01, 2018
Anticipated Completion DateDecember 31, 2019
Anticipated Primary Completion DateDecember 31, 2019
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • The proportion of EVD survivors with evidence of persistence of Ebola viral RNA in ocular tissue [Time Frame: Study completion]

  • Comparison of amount of intraocular inflammation, as measured by average grade of anterior chamber cell by SUN criteria, between EVD survivors and controls at 1 month and 3 months following cataract surgery. [Time Frame: 1 month and 3 months]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Proportion of survivors with at least 20/40 best corrected visual acuity after cataract surgery, relative to controls [Time Frame: Study completion]

  • Post-operative optical coherence tomography results in EVD survivors [Time Frame: Study completion]

  • Significance of covariates, age and gender, in logistic regression assessment of viral persistence and cataract outcomes [Time Frame: Study completion]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitlePREVAIL VII: Persistence of Ebola Virus in Aqueous Humor and Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease
Official TitlePREVAIL VII: Persistence of Ebola Virus in Aqueous Humor and Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease
Brief Summary

Objective: Zaire ebolavirus is a single-stranded RNA virus associated with high morbidity and mortality. The most recent epidemic of Ebola virus disease (EVD) in West Africa resulted in over 11,000 deaths and disabling sequelae among survivors, among which eye complications are highly represented. Chronic intraocular inflammation and viral persistence may result in posterior synechiae and cataract formation, resulting in loss of visual acuity and requiring surgical intervention to resolve. Approximately one out of ten Ebola survivors present with cataract, most of whom will require intraocular surgery during their lifetime, and many of whom require intervention in the near future to regain quality of life. For survivors who are blind from cataract, cataract extraction is necessary to restore visual function, allow reintegration into society and facilitate performance of activities of daily living.

However, surgical parameters among Ebola survivors are unknown, including whether Ebola viral RNA persists in aqueous humor, whether additional anti-inflammatory medication is needed, and the expected degree of improvement in visual function. Moreover, sites of viral persistence are unknown, and it is unclear if lens tissues removed during cataract surgery may harbor virus in Ebola-affected eyes. We propose following EVD survivors and control subjects undergoing cataract surgery to determine visual outcomes among Ebola survivors and explore detection of the presence of virus in lens tissues. The data will inform both future surgical intervention and aid in the understanding of the pathophysiology of Ebola-associated eye disease.

Study Population: Up to 60 Ebola survivors and up to 60 controls will be enrolled. The accrual ceiling is 120 participants.

Design: This is a prospective, natural history study to evaluate the persistence of Ebola viral RNA in the eyes of Ebola survivors and assess the response to cataract surgery in survivors as compared to controls. EVD survivors will first undergo assessment of aqueous humor for the presence of viral RNA. Survivors testing negative for viral RNA and control subjects will undergo clinically indicated cataract surgery. Subjects will be evaluated 1 day, 1 week, 1 month, and 3 months after surgery for safety and visual outcome assessments, and more often as clinically indicated.

Outcome Measures: The primary outcomes are: 1) the proportion of EVD survivors with evidence of persistence of Ebola viral RNA in ocular tissue and 2) the comparison of amount of intraocular inflammation, as measured by average grade of anterior chamber cell by SUN criteria, between EVD survivors and controls at 1 month and 3 months following cataract surgery. Secondary outcomes include: 1) the proportion of survivors with at least 20/40 best corrected visual acuity (BCVA) after cataract surgery, relative to controls; 2) significance of covariates, age and gender, in logistic regression assessment of viral persistence and cataract outcomes; 3) post-operative optical coherence tomography results in EVD survivors.

Detailed Description

Objective: Zaire ebolavirus is a single-stranded RNA virus associated with high morbidity and mortality. The most recent epidemic of Ebola virus disease (EVD) in West Africa resulted in over 11,000 deaths and disabling sequelae among survivors, among which eye complications are highly represented. Chronic intraocular inflammation and viral persistence may result in posterior synechiae and cataract formation, resulting in loss of visual acuity and requiring surgical intervention to resolve. Approximately one out of ten Ebola survivors present with cataract, most of whom will require intraocular surgery during their lifetime, and many of whom require intervention in the near future to regain quality of life. For survivors who are blind from cataract, cataract extraction is necessary to restore visual function, allow reintegration into society and facilitate performance of activities of daily living.

However, surgical parameters among Ebola survivors are unknown, including whether Ebola viral RNA persists in aqueous humor, whether additional anti-inflammatory medication is needed, and the expected degree of improvement in visual function. Moreover, sites of viral persistence are unknown, and it is unclear if lens tissues removed during cataract surgery may harbor virus in Ebola-affected eyes. We propose following EVD survivors and control subjects undergoing cataract surgery to determine visual outcomes among Ebola survivors and explore detection of the presence of virus in lens tissues. The data will inform both future surgical intervention and aid in the understanding of the pathophysiology of Ebola-associated eye disease.

Study Population: Up to 60 Ebola survivors and up to 60 controls will be enrolled. The accrual ceiling is 120 participants.

Design: This is a prospective, natural history study to evaluate the persistence of Ebola viral RNA in the eyes of Ebola survivors and assess the response to cataract surgery in survivors as compared to controls. EVD survivors will first undergo assessment of aqueous humor for the presence of viral RNA. Survivors testing negative for viral RNA and control subjects will undergo clinically indicated cataract surgery. Subjects will be evaluated 1 day, 1 week, 1 month, and 3 months after surgery for safety and visual outcome assessments, and more often as clinically indicated.

Outcome Measures: The primary outcomes are: 1) the proportion of EVD survivors with evidence of persistence of Ebola viral RNA in ocular tissue and 2) the comparison of amount of intraocular inflammation, as measured by average grade of anterior chamber cell by SUN criteria, between EVD survivors and controls at 1 month and 3 months following cataract surgery. Secondary outcomes include: 1) the proportion of survivors with at least 20/40 best corrected visual acuity (BCVA) after cataract surgery, relative to controls; 2) significance of covariates, age and gender, in logistic regression assessment of viral persistence and cataract outcomes; 3) post-operative optical coherence tomography results in EVD survivors.

Study TypeObservational
Study PhaseN/A
Estimated Enrollment
120
Allocation
Not Available
Interventional Model
Not Available
Masking
Not Available
Primary Purpose
Not Available
Conditions
Cataract
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodNon-Probability Sample
Study PopulationUp to 60 Ebola survivors and up to 60 controls will be enrolled.
Intervention
Not Available
Study Groups/Cohorts
Ebola Survivors
Up to 60 Ebola survivors will be enrolled.

Controls
Up to 60 controls will be enrolled.

Study Arms
Not Available
Arm Intervention/Treatment

Recruitment Information

Recruitment Status:Not yet recruiting
Enrollment120
Completion DateDecember 31, 2019
Eligibility Criteria: - INCLUSION CRITERIA:
To be eligible, the following inclusion criteria must be met, where applicable.
1. Participant must be 14 years of age or older.
2. Participant must be able to understand and sign an informed consent or have a parent/legal guardian do so if they are minor children or a legally authorized representative to provide consent for adults without consent capacity.
3. Participant must be either:
- an Ebola virus disease (EVD) seropositive survivor or seropositive control OR
- an EVD seronegative survivor or seronegative control (Serology confirmation is available for PREVAIL participants and will be conducted for non-PREVAIL participants.).
4. Participant must have visually significant cataract(s) consistent with level of visual deficit.
5. Participant must have corrected visual acuity worse than 20/40 in affected eye and vision loss believed to be primarily the result of the cataract.
6. Any participant of childbearing potential must have a negative pregnancy test at screening and must be willing to undergo pregnancy testing prior to the cataract surgery.
EXCLUSION CRITERIA:
A participant is not eligible if any of the following exclusion criteria are present.
1. Concurrent life-threatening illness or other condition that compromises a participant s ability to safely undergo surgery, as determined by the surgical and medical team, including any condition that prevents the participant from lying down supine or remaining still, such as severe lung disease, or a known life-threatening, untreated or unstable cardiac or pulmonary condition.
2. Active uveitis at time of surgery or within the past three months, if documented.
3. Participant is pregnant, as surgery is elective and no adequate data regarding the use of postoperative topical antibiotic-steroid combination drops exists in pregnant women.
4. Any condition that poses a risk to the participant having a safe surgical or post-operative experience, including known inability or unwillingness to follow up for the full duration of the protocol.
GenderAll
Age14 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Liberia

Administrative Information

NCT Number:NCT03309020
Other Study ID Numbers
999917167
17-EI-N167
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
National Eye Institute (NEI)
Collaborators
Not Available
Investigators
Principal Investigator
Rachel J Bishop, M.D.
National Eye Institute (NEI)