INflammatory MediatorS in the PathophysIology of Diabetic REtinopathy Study

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

164 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-09

Study Completion Date

2026-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The central hypothesis is that inflammation mediators are biomarkers of both systemic diabetes and Diabetic Retinopathy (DR) progression in the aqueous and that sustained topical ketorolac application reduces/suppresses those inflammatory mediators thereby reducing the progression of Diabetic Retinopathy.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Topic Ketorolac Added to Panphotocoagulation in Proliferative Diabetic Retinopathy

NCT00907114

Proliferative Diabetic Retinopathy Macular Edema

COMPLETED PHASE2

Octreotide Acetate in Microspheres in Patients With Diabetic Retinopathy

NCT00131144

Diabetic Retinopathy

COMPLETED PHASE3

Aflibercept Injection for Proliferative Diabetic Retinopathy

NCT01805297

Vitreous Hemorrhage

COMPLETED PHASE2

An Investigator-Initiated Study to Assess the Association of Diabetic Retinopathy Severity Scale (DRSS) With Level of Decreased Corneal Sensitivity

NCT05566717

Diabetic Retinopathy Neurotrophic Keratitis

UNKNOWN

Octreotide Acetate in Microspheres in Patients With Diabetic Retinopathy

NCT00130845

Diabetic Retinopathy

COMPLETED PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Study goals include confirming inflammation mediators are biomarkers of both systemic diabetes and DR progression in the aqueous. Like the vitreous humor, the aqueous reflects localized ocular inflammation, however, is technically easier to collect with less risk. The investigators will also determine the long-term effects of sustained ketorolac application on intraocular cytokine levels, DR progression, and diabetic macular edema (DME) incidence. The proposal is the first to use a cornea-permeable Nonsteroidal anti-inflammatory drug (NSAID) for the treatment of DR.

It is believed local inflammation control in the eye will transform future treatment options for diabetic patients facing blindness. Tracking and inhibiting local inflammatory mediators through all DR stages has the capacity to reduce or prevent disability in millions of patients per year.

164 adult type II diabetic mellitus (T2DM) patients, aged 18 years or greater will be enrolled to measure aqueous PGE2 and inflammatory cytokines. Because the pathophysiology of type I disease and the population it effects are different, type I diabetic patients will be excluded. Diabetic retinopathy is broadly categorized as nonproliferative (NPDR) and proliferative (PDR). The international Clinical Disease Severity Scale is a standard classification system consisting of two categories and five stages: the nonproliferative category, stage 1-4 and proliferative category, stage 5. Stage 1 is characterized as "no apparent retinopathy." The nonproliferative stage is further grouped into stage 2 (mild), stage 3 (moderate), and stage 4 (severe). Stage 5 is final stage, PDR.

Of the 164 patients enrolled for aqueous PGE2 and inflammatory cytokine measurements, the diabetic participants corresponding to stages 1, 3, and 5 will be classified as patients with no DR (23 patients), with PDR (23 patients), and with moderate NPDR (118 patients). The 118 participants with moderate NPDR will be randomized for Aim 2 described below.

In addition, 100 age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole will be enrolled as controls.

Aim 1 of this project is to measure aqueous PGE2 and inflammatory cytokines during DR progression.

Aim 2 of this project is two-fold:

1. Investigate the long-term effects of daily topical application of ketorolac on PGE2 and cytokine levels.
2. Determine how topical application of ketorolac influences DR progression and development of DME.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Diabetic Retinopathy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a 2 aim, randomized and double-masked Phase I study on topical Ketorolac for the prevention of diabetic retinopathy.

164 adult type II diabetic patients, aged 18 years or greater will be enrolled in addition to 100 age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole will also be enrolled.

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

At the baseline visit, only patients from the moderate NPDR group will be randomized into one of 2 groups, using a red cap database for randomization in a block manner to ensure near equal randomization in both groups.

A report is generated every 4 months for assessment of the number of patients in each randomized category.

Patients in this group will have both eyes randomized to either Acuvail or placebo-control (preservative-free artificial tear) in double-masked fashion.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Adult Type II Diabetics - Moderate NPDR - Ketorolac

59 Adult type II diabetic patients with baseline moderate non-proliferative diabetic retinopathy and HbA1c ≥ 8 randomized to Ketorolac treatment.

Group Type EXPERIMENTAL

Ketorolac 0.45% ophthalmic solution

Intervention Type DRUG

Ketorolac 0.45% ophthalmic solution 1 drop instilled in both eyes twice daily for 3 years in double-masked fashion.

Aqueous PGE2 and inflammatory cytokines measurements

Intervention Type OTHER

After topical anesthetic, antibiotic and 5% povidone-iodine application, a 30 gauge needle on a 1 ml tuberculin syringe will be inserted into the anterior chamber and used to collect 0.1 ml of aqueous fluid from each eye. Aqueous PGE2 and Inflammatory cytokines will be measured

Adult Type II Diabetics - Moderate NPDR - Placebo

59 Adult type II diabetic patients with baseline moderate non-proliferative diabetic retinopathy randomized to placebo treatment.

Group Type PLACEBO_COMPARATOR

Placebo - Preservative-free artificial tears

Intervention Type DRUG

Preservative free artificial tears ophthalmic solution 1 drop instilled in both eyes twice daily for 3 years in double-masked fashion.

Aqueous PGE2 and inflammatory cytokines measurements

Intervention Type OTHER

After topical anesthetic, antibiotic and 5% povidone-iodine application, a 30 gauge needle on a 1 ml tuberculin syringe will be inserted into the anterior chamber and used to collect 0.1 ml of aqueous fluid from each eye. Aqueous PGE2 and Inflammatory cytokines will be measured

Adult Type II Diabetics - No Diabetic Retinopathy (DR)

23 Adult type II diabetic patients with no diabetic retinopathy as a control group.

Group Type OTHER

Aqueous PGE2 and inflammatory cytokines measurements

Intervention Type OTHER

After topical anesthetic, antibiotic and 5% povidone-iodine application, a 30 gauge needle on a 1 ml tuberculin syringe will be inserted into the anterior chamber and used to collect 0.1 ml of aqueous fluid from each eye. Aqueous PGE2 and Inflammatory cytokines will be measured

Adult Type 2 Diabetics-Proliferative Diabetic Retinopathy(PDR)

23 Adult type II diabetic patients with proliferative diabetic retinopathy as a control group.

Group Type OTHER

Aqueous PGE2 and inflammatory cytokines measurements

Intervention Type OTHER

After topical anesthetic, antibiotic and 5% povidone-iodine application, a 30 gauge needle on a 1 ml tuberculin syringe will be inserted into the anterior chamber and used to collect 0.1 ml of aqueous fluid from each eye. Aqueous PGE2 and Inflammatory cytokines will be measured

Age-matched Non-diabetics

We will also enroll 100 age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole. Removed aqueous fluid that is typically discarded will instead be collected and stored at -80° C. Aqueous fluid will be tested for inflammatory markers as detailed below to provide a reference level for cross-comparison analysis.

Group Type OTHER

Aqueous PGE2 and inflammatory cytokines measurements

Intervention Type OTHER

After topical anesthetic, antibiotic and 5% povidone-iodine application, a 30 gauge needle on a 1 ml tuberculin syringe will be inserted into the anterior chamber and used to collect 0.1 ml of aqueous fluid from each eye. Aqueous PGE2 and Inflammatory cytokines will be measured

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Ketorolac 0.45% ophthalmic solution

Ketorolac 0.45% ophthalmic solution 1 drop instilled in both eyes twice daily for 3 years in double-masked fashion.

Intervention Type DRUG

Placebo - Preservative-free artificial tears

Preservative free artificial tears ophthalmic solution 1 drop instilled in both eyes twice daily for 3 years in double-masked fashion.

Intervention Type DRUG

Aqueous PGE2 and inflammatory cytokines measurements

After topical anesthetic, antibiotic and 5% povidone-iodine application, a 30 gauge needle on a 1 ml tuberculin syringe will be inserted into the anterior chamber and used to collect 0.1 ml of aqueous fluid from each eye. Aqueous PGE2 and Inflammatory cytokines will be measured

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Acuvail Refresh

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Inclusion Criteria:

* Aim 1 Diabetic Arm Inclusion Criteria: Adult patients age 18 years or greater with type II diabetes.
* Aim 1 Nondiabetic Control Arm Inclusion Criteria: age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole.
* Aim 2 Inclusion Criteria: Adult patients age 18 years or older with type II diabetes, with baseline moderate NPDR and HbA1c ≥ 8.

Exclusion Criteria:

* Aim 1 Diabetic Arm Exclusion Criteria: Patients with a history of previous vitrectomy in either eye; prior intravitreal injection within 3 months; co-existent macular, retinovascular, or inflammatory disease; history of ocular trauma; aphakia; presence of an anterior chamber intraocular lens; current use of prescription systemic NSAIDs or regular use of nonprescription NSAIDs including aspirin (defined as 4 days or more a week for at least 2 weeks a month); blood pressure \> 180/110 mmHg; risk for corneal melting; and inability to comply with follow-up.
* Aim 1 Nondiabetic Control Arm Exclusion Criteria: Patients who are unable to comply with testing and follow-up.
* Aim 2 Exclusion Criteria: Patients with a history of previous vitrectomy in either eye; prior intravitreal injection within 3 months; co-existent macular, retinovascular, or inflammatory disease; history of ocular trauma; aphakia; presence of an anterior chamber intraocular lens; current use of prescription systemic NSAIDs or regular use of nonprescription NSAIDs including aspirin (defined as 4 days or more a week for at least 2 weeks a month); blood pressure \> 180/110 mmHg; risk for corneal melting; and inability to comply with follow-up.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No