The Role of Prostaglandins in the Progression of Diabetic Retinopathy (Prostaglandin)

February 20, 2017 updated by: Stephen J. Kim, MD, Vanderbilt University

The Role of Prostaglandins in the Progression of Diabetic Retinopathy and the Therapeutic Efficacy of Topical Ketorolac (Acuvail)

Objective of the research study:

  1. To measure anterior chamber and vitreous ketorolac (Acuvail®) concentrations after topical administration in patients undergoing routine vitrectomy to determine the ability of the medication to penetrate into the anterior chamber and vitreous cavity, and to compare these levels to the IC50 for the cyclooxygenase-1 and -2 enzymes (COX-1 and COX-2)
  2. To measure vitreous concentrations of prostaglandin subtypes (PGE, PGD, PGF) and other inflammatory mediators (Interleukin-1β [IL-1β], IL-6, IL-8, tumor necrosis factor [TNF]-α, VEGF) in both diabetic and nondiabetic patients undergoing vitrectomy
  3. To determine if topical ketorolac (Acuvail®) can penetrate the anterior chamber and vitreous cavity sufficiently to decrease levels of intraocular inflammatory mediators that have been shown to be elevated in diabetic patients
  4. To serve as a precursor to a 5-year longitudinal clinical trial to determine if chronically administered topical ketorolac (Acuvail®) can prevent, delay or slow diabetic retinopathy.

Research hypothesis

  1. Ketorolac (Acuvail®) will penetrate the anterior chamber and vitreous cavity sufficiently to achieve levels above the IC50 for COX-1 and COX-2
  2. Prostaglandin and other inflammatory mediator levels in the anterior chamber and vitreous cavity will be significantly higher among diabetic patients than nondiabetic controls
  3. Acuvail® can significantly lower anterior chamber and vitreous cavity levels of prostaglandins and other inflammatory mediators in diabetic patients

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Patients who require vitrectomy for any indication and those meeting the inclusion/exclusion criteria will be included. Patients will be consented to participate in the study and for surgery.

Nondiabetic patients will be included in one of two groups. Twenty will receive topical ketorolac (Acuvail®) preoperatively for 3 days and then samples will be taken at the time of surgery. Twenty other patients will serve as controls for intraocular prostaglandin and cytokine levels (to be compared to diabetic patients). This group will not receive preoperative ketorolac (Acuvail®).

Diabetic patients will be included in one of two groups. Twenty patients will have intraocular prostaglandin and cytokine levels measured. Twenty other patients will be in the interventional group to determine if topical ketorolac (Acuvail®) can successfully lower intraocular prostaglandin and inflammatory cytokine levels.

In all cases, patients are undergoing vitreoretinal surgery as the surgical treatment of choice for their condition. For this study, undiluted samples will be drawn from the vitreous cavity and anterior chamber at the beginning of the vitrectomy. These samples will be stored, analyzed and frozen.

Samples will be tested for prostaglandin levels, in addition to other inflammatory cytokines, and ketorolac levels.

Three days of Acuvail® given four times per day was chosen, as previous studies have shown that one dose of ketorolac 0.4% achieves a peak aqueous concentration of 57.5 ng/mL,1 and that 12 doses over two days achieves an aqueous concentration of 1079 ng/mL.2 Both values are well above the IC50 for COX-1 (5.3 to 7.5 ng/mL) and COX-2 (33.9-45.2 ng/mL). The upper end of this dosing spectrum was chosen, as more doses and a longer duration of therapy is likely required to achieve sufficient vitreous levels to inhibit COX-1 and COX-2. This dosing regimen was also used in another clinical study that assessed ketorolac levels and prostaglandin levels in the vitreous cavity after topical administration four times a day for three days preoperatively.3

Study Type

Interventional

Phase

  • Phase 1

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

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232-8808
        • Vanderbilt Eye Institute

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 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Adult patients aged 18 years or older who present for vitrectomy surgery for any indication.
  2. Diabetic and non-diabetic patients will be included.

Exclusion criteria:

  1. Patients under the age of 18 years of age.
  2. Pregnant women.
  3. Patients with a history of vitrectomy surgery.
  4. Current topical, periocular, intraocular or systemic corticosteroid use
  5. Co-existent macular, retinovascular or ocular inflammatory disease (age-related macular degeneration, retinal venous occlusive disease, uveitis, etc.)

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: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Acuvail
Acuvail as preventive for inflammation and possible decrease or prevent diabetic retinopathy. The study has four arms - diabetic ketorolac, diabetic control, normal eyes ketorolac, normal eyes control. patients are randomized to ketorolac or control.
Drug: Acuvail
Dosing of drug 3 days prior to surgery
Other Names:
  • Ketorolac 0.45%
Placebo Comparator: Placebo
Placebo using artificial tear drops
Other: Placebo
Artificial tears qid for 3 days preoperatively
Other Names:
  • tears

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail
Time Frame: 3 days
Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail
3 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Outcome
Time Frame: 7 days
The primary outcomes include drug and prostaglandin concentrations on the anterior chamber and vitreous.
7 days
Secondary Outcome
Time Frame: 14 days
The secondary outcome will include cytokine levels in the vitreous.
14 days

Collaborators and Investigators

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

Sponsor

Vanderbilt University

Investigators

  • Principal Investigator: Stephen J Kim, MD, Vanderbilt Eye Institute

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)

March 1, 2012

Primary Completion (Actual)

October 19, 2016

Study Completion (Actual)

October 19, 2016

Study Registration Dates

First Submitted

March 27, 2012

First Submitted That Met QC Criteria

May 29, 2012

First Posted (Estimate)

June 1, 2012

Study Record Updates

Last Update Posted (Actual)

February 23, 2017

Last Update Submitted That Met QC Criteria

February 20, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12022 (DAIDS-ES Registry Number)

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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