The Role of Prostaglandins in the Progression of Diabetic Retinopathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Stephen J. Kim, MD, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01609881
First received: March 27, 2012
Last updated: December 30, 2013
Last verified: December 2013
  Purpose

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

Condition Intervention
Inflammation
Drug: Acuvail
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: The Role of Prostaglandins in the Progression of Diabetic Retinopathy and the Therapeutic Efficacy of Topical Ketorolac (Acuvail)

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail


Secondary Outcome Measures:
  • Primary Outcome [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    The primary outcomes include drug and prostaglandin concentrations on the anterior chamber and vitreous.

  • Secondary Outcome [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    The secondary outcome will include cytokine levels in the vitreous.


Estimated Enrollment: 100
Study Start Date: March 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Ketorolac 0.45%
Placebo Comparator: Placebo
Placebo using artificial tear drops
Other: Placebo
Artificial tears qid for 3 days preoperatively
Other Name: tears

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

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01609881

Contacts
Contact: Stephen J Kim, MD 615-936-2020 steve.kim@vanderbilt.edu
Contact: Sandy A Owings 615-936-1474 sandy.owings@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt Eye Institute Recruiting
Nashville, Tennessee, United States, 37232-8808
Contact: Sandy A Owings    615-936-1474    sandy.owings@vanderbilt.edu   
Contact: Lisa Pate    615-936-3465    lisa/pate@vanderbilt.edu   
Sub-Investigator: Scott D Schoenberger, MD         
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Stephen J Kim, MD Vanderbilt Eye Institute
  More Information

No publications provided by Vanderbilt University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Stephen J. Kim, MD, Assistant Professor of Ophthalmology, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01609881     History of Changes
Other Study ID Numbers: 12022
Study First Received: March 27, 2012
Last Updated: December 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Inflammation

Additional relevant MeSH terms:
Diabetic Retinopathy
Inflammation
Retinal Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Pathologic Processes
Ophthalmic Solutions
Ketorolac
Ketorolac Tromethamine
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 01, 2014