The Role of Prostaglandins in the Progression of Diabetic Retinopathy

NCT01609881 | Withdrawn Phase 1

• 1 other identifier: 12022
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Objective of the research study:

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

Conditions

Inflammation

Keywords

Inflammation

Outcome Measures

Primary Outcomes (1)

• Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail

  Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail

  3 days

Secondary Outcomes (2)

• Primary Outcome

  7 days

• Secondary Outcome

  14 days

Study Arms (2)

Acuvail

OTHER

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

Placebo

PLACEBO COMPARATOR

Placebo using artificial tear drops

Other: Placebo

Interventions

Acuvail DRUG

Dosing of drug 3 days prior to surgery

Also known as: Ketorolac 0.45%

Acuvail

Placebo OTHER

Artificial tears qid for 3 days preoperatively

Also known as: tears

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt Eye Institute

Nashville, Tennessee, 37232-8808, United States

Location

Related Publications (3)

• Schoenberger SD, Kim SJ, Shah R, Sheng J, Cherney E. Reduction of interleukin 8 and platelet-derived growth factor levels by topical ketorolac, 0.45%, in patients with diabetic retinopathy. JAMA Ophthalmol. 2014 Jan;132(1):32-7. doi: 10.1001/jamaophthalmol.2013.6203.

  PMID: 24336915 DERIVED

• Schoenberger SD, Kim SJ, Sheng J, Calcutt MW. Reduction of vitreous prostaglandin E2 levels after topical administration of ketorolac 0.45%. JAMA Ophthalmol. 2014 Feb;132(2):150-4. doi: 10.1001/jamaophthalmol.2013.5692.

  PMID: 24264034 DERIVED

• Schoenberger SD, Kim SJ, Sheng J, Rezaei KA, Lalezary M, Cherney E. Increased prostaglandin E2 (PGE2) levels in proliferative diabetic retinopathy, and correlation with VEGF and inflammatory cytokines. Invest Ophthalmol Vis Sci. 2012 Aug 27;53(9):5906-11. doi: 10.1167/iovs.12-10410.

  PMID: 22871833 DERIVED

MeSH Terms

Conditions

Inflammation

Interventions

Ketorolac

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Stephen J Kim, MD

  Vanderbilt Eye Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Ophthalmology

Study Record Dates

• First Submitted: March 27, 2012
• First Posted: June 1, 2012
• Study Start: March 1, 2012
• Primary Completion: October 19, 2016
• Study Completion: October 19, 2016
• Last Updated: February 23, 2017

Record last verified: 2017-02

Locations

US (1)