Effects of Topical Insulin on Corneal Epithelium Healing After Corneal Crosslinking in Patients With Keratoconus

NCT06601101 | Recruiting Phase 3

• 2 other identifiers: 77229224.8.0000.5404Topical Insulin
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The cornea plays a fundamental role in vision, being a complex tissue essential for ocular health. In ophthalmological practice, there are situations such as corneal crosslinking, where damage to the corneal epithelium occurs. Crosslinking is a surgical procedure aimed at strengthening collagen bonds in the corneal stroma to prevent the progression of keratoconus, through the application of topical riboflavin followed by ultraviolet (UV-A) radiation. To enhance the effectiveness of riboflavin and UV-A radiation, the corneal epithelium needs to be removed, which can cause postoperative pain and discomfort, as well as increase the risk of complications such as infections, scarring, corneal opacities, perforations, and recurrent epithelial erosions. Several growth factors play a role in epithelial healing, and the discovery of insulin in the tear film and the presence of insulin and Insulin-Like Growth Factor (IGF-1) receptors in the cornea has raised the hypothesis that insulin may modulate the cornea's wound healing response. Since then, topical insulin has been used for various ocular pathologies, including dry eye disease, persistent epithelial defects, and neurotrophic ulcers. Based on this knowledge, studies have been developed, and promising results regarding the use of insulin in corneal healing have been reported, providing a scientific foundation for the realization of this project. The objective of this study is to evaluate the effect of insulin eye drops at a concentration of 50 IU/ml on epithelial healing in non-diabetic patients undergoing epithelial debridement for corneal crosslinking. To this end, a randomized, double-masked clinical trial will be conducted with two groups, one being the control group, in which researchers will compare the epithelial healing rate in mm²/h between the insulin group and the placebo group, as the primary outcome. Patients diagnosed with keratoconus and with an indication for the crosslinking procedure, will be invited to participate. As a result of the study, it is expected to assess and quantify the impact of topical insulin on epithelial defect closure in patients undergoing crosslinking, compared to placebo. Topical insulin may contribute to early epithelial defect closure, control of inflammation, and prevention of complications that could significantly impact visual quality.

Conditions

Keratoconus; Cornea Disease; Eye Diseases; Wound Heal

Keywords

Topical Insulin; Crosslinking

Outcome Measures

Primary Outcomes (1)

• Corneal Epithelial Healing Rate

  Epithelial healing rate, measured daily using images obtained with the Keratograph - OCULUS® and analyzed using ImageJ software (https://imagej.nih.gov/ij/)

  7 days

Secondary Outcomes (2)

• Endothelial cell count

  60 days

• Incidence of corneal haze

  60 days

Study Arms (2)

Group A

ACTIVE COMPARATOR

Insulin eye drops 50 IU/ml (1 drop every 6 hours)

Drug: Insulin

Group B

PLACEBO COMPARATOR

Placebo eye drops of 0.5% Methylcellulose (1 drop every 6 hours)

Drug: Placebo eye drops of 0.5% Methylcellulose

Interventions

Insulin DRUG

Insulin eye drops in the postoperative prescription for corneal crosslinking

Group A

Placebo eye drops of 0.5% Methylcellulose DRUG

Placebo eye drops of 0.5% Methylcellulose in the postoperative prescription for corneal crosslinking

Also known as: Placebo

Group B

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a diagnosis of keratoconus, indicated for corneal crosslinking

You may not qualify if:

• Diabetes Mellitus
• Severe dry eye
• Limbal Stem Cell Deficiency
• Glaucoma
• Insulin or methylcellulose allergy

Sponsors & Collaborators

• University of Campinas, Brazil: lead

Study Sites (1)

State University of Campinas

Campinas, São Paulo, 13.083-887, Brazil

RECRUITING

MeSH Terms

Conditions

Keratoconus; Corneal Diseases; Eye Diseases

Interventions

Insulin; Methylcellulose

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Cellulose; Glucans; Polysaccharides; Carbohydrates

Study Officials

• Monica Alves, PhD

  State University of Campinas (Unicamp)

  STUDY CHAIR

Central Study Contacts

Vitor Guimarães, MD

CONTACT

+55 64 99658-8797; vitorborgesguimaraes@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: After the assignment of interventions, the patient will be masked, and the research team conducting the postoperative examinations will also be masked. The assisting team performing the crosslinking will document in the research log which group the study participant belongs to. The researchers conducting the evaluations of the participants will only have access to this information at the end of the study for data analysis. In the case of suspected complications, an ophthalmologist independent of the cornea service will evaluate the patient and determine the most appropriate course of action.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: The participants will be distributed in blocks of four and stratified by gender: four small envelopes, two from each intervention group, will be sealed and placed in a larger envelope, totaling 10 larger envelopes. This ensures that in each block of four participants, two participants from each studied group will be included.

Study Record Dates

• First Submitted: September 15, 2024
• First Posted: September 19, 2024
• Study Start: August 1, 2024
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)