Ketorolac Eye Drops for Diabetic Retinopathy

(INSPIRE Trial)

Overseen By Crystal Nicholson

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stephen J. Kim, MD

Must not be taking: NSAIDs, Aspirin

Disqualifiers: Vitrectomy, Macular disease, Hypertension, others

Compensation: Varies

Number of Visits: 4

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ketorolac eye drops (ketorolac 0.45% ophthalmic solution) to determine if they can slow the progression of diabetic retinopathy, a serious eye condition caused by diabetes that can lead to vision loss. Researchers aim to discover if ketorolac can reduce inflammation associated with both diabetes and the eye disease. The trial includes different groups, such as individuals with type II diabetes who have moderate diabetic retinopathy and those without the condition. Individuals with type II diabetes and frequent blood sugar levels of 8% or higher may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

If you are currently using prescription systemic NSAIDs or regularly using nonprescription NSAIDs like aspirin, you will need to stop taking them to participate in this trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ketorolac 0.45% eye drops are generally safe. One study found that these eye drops reached high levels in the eye, indicating effectiveness without preservatives. This is important because preservatives can sometimes cause irritation. Another study found that ketorolac eye drops reduced inflammation and pain after cataract surgery, suggesting they are well-tolerated by most people.

Although this trial is in its early stages, ketorolac eye drops have been approved for other eye conditions. They have already passed safety checks for those uses, indicating general safety for the eyes. However, always consult the study team or a healthcare provider for personal advice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for diabetic retinopathy?

Unlike the standard treatments for diabetic retinopathy, which often include laser therapy or anti-VEGF injections, Ketorolac eye drops offer a non-invasive approach. Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) that works by reducing inflammation, potentially addressing some underlying issues of diabetic retinopathy without the need for injections or surgery. Researchers are excited because this could mean easier and less invasive management of diabetic retinopathy, with the possibility of reducing inflammation directly in the eyes through simple, regular eye drop application.

What evidence suggests that ketorolac eye drops might be an effective treatment for diabetic retinopathy?

Research has shown that ketorolac 0.45% eye drops can reduce swelling and pain after cataract surgery in people with diabetes, potentially improving vision. Studies have found that this treatment significantly lowers signs of inflammation. In diabetes, inflammation can worsen eye conditions like diabetic retinopathy. By reducing inflammation, ketorolac may help slow the progression of diabetic retinopathy. In this trial, some participants will receive ketorolac treatment, while others will receive a placebo of preservative-free artificial tears. This makes ketorolac a promising option for managing eye health in people with diabetes. ^{1 3 4 5 6}

Who Is on the Research Team?

Stephen J Kim, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with type II diabetes and moderate Diabetic Retinopathy (DR), specifically those with an HbA1c ≥ 8. It's also for age-matched non-diabetics needing vitrectomy surgery without inflammation. Excluded are individuals with ocular trauma, certain eye conditions, high blood pressure, or using NSAIDs regularly.

Inclusion Criteria

I am an adult with type II diabetes.

I am 18 or older with type II diabetes, moderate NPDR, and HbA1c ≥ 8.

I am of similar age, don't have diabetes, and need surgery for a non-inflammatory eye condition.

Exclusion Criteria

I have a disease affecting the macula, blood vessels in the eye, or eye inflammation.

Aim 1 Diabetic Arm: Inability to comply with follow-up

Aim 2: Inability to comply with follow-up

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily topical application of ketorolac or placebo to study its effects on PGE2 and cytokine levels, and DR progression

1 year

Visits every 4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression of DR and DME

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Ketorolac 0.45% ophthalmic solution
• Placebo - Preservative-free artificial tears

Trial Overview The study tests if topical ketorolac eye drops can reduce inflammatory mediators in the eyes of diabetic patients and slow DR progression compared to placebo (artificial tears). Measurements of PGE2 and cytokines in the aqueous part of the eye will help assess this.

How Is the Trial Designed?

Group I: Age-matched Non-diabetics Experimental Treatment 1 Intervention

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 II: Adult Type II Diabetics - No Diabetic Retinopathy (DR) Experimental Treatment 1 Intervention

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

Group III: Adult Type II Diabetics - Moderate NPDR - Ketorolac Experimental Treatment 2 Interventions

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

Group IV: Adult Type 2 Diabetics-Proliferative Diabetic Retinopathy(PDR) Experimental Treatment 1 Intervention

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

Group V: Adult Type II Diabetics - Moderate NPDR - Placebo Placebo Group 2 Interventions

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

Who Is Running the Clinical Trial?

Stephen J. Kim, MD

Lead Sponsor

Trials

1

Recruited

160+

Allergan

Industry Sponsor

Trials

782

Recruited

277,000+

Brent Saunders

Allergan

Chief Executive Officer since 2015

JD and MBA from Temple University

Dr. David Nicholson

Allergan

Chief Medical Officer since 2015

MD from Harvard Medical School

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3699301/

Prophylactic postoperative ketorolac improves outcomes in ... Conclusion. Prophylactic postoperative ketorolac 0.4% may have a role in reducing the frequency and severity of CME in diabetic eyes post-cataract surgery.

2. withpower.com withpower.com/trial/phase-1-retinal-diseases-10-2020-9a5ed

Ketorolac Eye Drops for Diabetic Retinopathy (INSPIRE Trial) Ketorolac 0.45% eye drops have been shown to reduce inflammation and pain after cataract surgery, and they may help improve visual function in diabetic patients ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02646072

Effect of Preoperative Topical Ketorolac on Aqueous ... To compare aqueous levels of inflammatory cytokines in diabetic and non diabetic patients treated with preoperative topical ketorolac tromethamine 0.45%.

4. researchgate.net researchgate.net/publication/51459975_Ketorolac_045_Ophthalmic_Solution

Ketorolac 0.45% Ophthalmic Solution | Request PDF Compared with placebo, topical ketorolac 0.45% ophthalmic solution significantly increased the proportion of patients who were pain-free on the day after ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10347851/

The effect of topical ketorolac tromethamine on macular ... Based on our findings, topical ketorolac tromethamine 0.5% is not effective in the prevention of post-phacoemulsification macular thickening in diabetic ...

6. jamanetwork.com jamanetwork.com/journals/jamaophthalmology/fullarticle/1790181

Topical Ketorolac in Diabetic Retinopathy Ketorolac tromethamine, 0.45%, is preservative free and achieves 2.5-fold higher vitreous levels than older formulations. Its excellent safety, enhanced ...