Topical Insulin Drops for the Treatment of Neurotrophic Keratopathy.

NCT05321251 | Withdrawn Phase 2 DMC

• 1 other identifier: Pro00107280
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

Brief Summary

Many diseases can affect corneal nerves. Corneas that lack normal sensation are considered neurotrophic. Neurotrophic corneas are predisposed to persistent epithelial defects, recurrent erosions, and corneal ulcers. These can lead to a variety of complications, from subjective pain, discomfort, and blurry vision, to corneal perforation and endophthalmitis. Neurotrophic corneas and the persistent epithelial defects associated with them can be very difficult to treat. Non-invasive measures include topical drops (artificial tears, antibiotics, or steroids), bandage contact lens, and punctal plugs. More invasive surgical treatments include membrane grafts, tarsorrhaphy, and keratoplasty. Despite these treatments, many neurotrophic corneas still do not heal. This study aims to test the efficacy of topical insulin in the treatment of neurotrophic keratopathy.

Conditions

Neurotrophic Keratitis

Keywords

topical insulin; neurotrophic keratopathy; neurotrophic keratitis; tarsorrhaphy

Outcome Measures

Primary Outcomes (1)

• Time to re-epithelialization of neurotrophic ulcer

  Time taken for re-epithelialization of the neurotrophic ulcer which will be defined as \<0.5 mm of the remaining epithelial defect

  3 months

Study Arms (2)

Topical insulin

EXPERIMENTAL

Topical insulin (Humulin R) will be compounded under sterile conditions at a local pharmacy at a concentration of 25 IU / ml in sterile balanced saline solution (0.9%). Topical insulin will be administered four times per day to the affected eye. A bottle of topical insulin can be used for 14 days. Any remaining topical insulin will be discarded as waste after 14 days.

Drug: Insulin

Tarsorrhaphy

ACTIVE COMPARATOR

Patients in this group will receive a temporary, central tarsorrhaphy and will not use additional eye drops.

Procedure: Tarsorrhaphy

Interventions

Insulin DRUG

see arm description

Topical insulin

Tarsorrhaphy PROCEDURE

see arm description

Tarsorrhaphy

Eligibility Criteria

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

You may qualify if:

• Diagnosis of neurotrophic keratitis with persistent epithelial defect that has been refractory to conventional treatments for at least 2 weeks
• years or older
• Able to provide informed consent
• Failed other conventional treatments for neurotrophic keratitis
• Understanding and accepting of use of topical insulin alone

You may not qualify if:

• Less than 18 years old
• Pregnant or breastfeeding women
• Unable to provide informed consent
• Unable to comply with tests/follow-up
• Lid function abnormalities (e.g., lagophthalmos, entropion, ectropion, or abnormal orbicularis function from cranial nerve 7 palsy or Bell's palsy)
• Patients who require ongoing topical treatment (e.g. topical ganciclovir)

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (6)

University of Alberta

Edmonton, Alberta, T6G 2C8, Canada

Location

University of British Columbia

Vancouver, British Columbia, Canada

Location

Dalhousie University

Halifax, Nova Scotia, Canada

Location

Precision Cornea Clinic

Ottawa, Ontario, Canada

Location

University of Toronto

Toronto, Ontario, Canada

Location

University of Montreal

Montreal, Quebec, Canada

Location

Related Publications (6)

• Galvis V, Nino CA, Tello A, Grice JM, Gomez MA. Topical insulin in neurotrophic keratopathy after resection of acoustic neuroma. Arch Soc Esp Oftalmol (Engl Ed). 2019 Feb;94(2):100-104. doi: 10.1016/j.oftal.2018.06.003. Epub 2018 Jul 17. English, Spanish.

  PMID: 30025986 BACKGROUND

• Bastion ML, Ling KP. Topical insulin for healing of diabetic epithelial defects?: A retrospective review of corneal debridement during vitreoretinal surgery in Malaysian patients. Med J Malaysia. 2013 Jun;68(3):208-16.

  PMID: 23749008 BACKGROUND

• Fai S, Ahem A, Mustapha M, Mohd Noh UK, Bastion MC. Randomized Controlled Trial of Topical Insulin for Healing Corneal Epithelial Defects Induced During Vitreoretinal Surgery in Diabetics. Asia Pac J Ophthalmol (Phila). 2017 Sep-Oct;6(5):418-424. doi: 10.22608/APO.201780. Epub 2017 Aug 22.

  PMID: 28828764 BACKGROUND

• Tong CM, Iovieno A, Yeung SN. Topical insulin for neurotrophic corneal ulcers. Can J Ophthalmol. 2020 Oct;55(5):e170-e172. doi: 10.1016/j.jcjo.2020.04.001. Epub 2020 May 13. No abstract available.

  PMID: 32416928 BACKGROUND

• Diaz-Valle D, Burgos-Blasco B, Gegundez-Fernandez JA, Garcia-Caride S, Puebla-Garcia V, Pena-Urbina P, Benitez-Del-Castillo JM. Topical insulin for refractory persistent corneal epithelial defects. Eur J Ophthalmol. 2021 Sep;31(5):2280-2286. doi: 10.1177/1120672120958307. Epub 2020 Sep 21.

  PMID: 32951459 BACKGROUND

• Wang AL, Weinlander E, Metcalf BM, Barney NP, Gamm DM, Nehls SM, Struck MC. Use of Topical Insulin to Treat Refractory Neurotrophic Corneal Ulcers. Cornea. 2017 Nov;36(11):1426-1428. doi: 10.1097/ICO.0000000000001297.

  PMID: 28742619 RESULT

MeSH Terms

Interventions

Insulin

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Christopher J Rudnisky, MD MPH

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Treatment will be randomized / assigned randomly, but neither the patients, care providers, or investigators will be masked to treatment once it is being provided.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a randomized controlled trial for the treatment of neurotrophic keratitis. Topical insulin drops will be compared to the current gold standard treatment temporary tarsorrhaphy. Patients will be recruited in Vancouver, Edmonton, Toronto, Montreal, and Halifax. Patients with neurotrophic corneal ulcers will be identified through the Ophthalmology on call resident clinics in each location. They will be directly referred to a physician in their city who is participating in this study. At least 12 patients will be enrolled in each group (as per power calculation): topical insulin drops or tarsorrhaphy.

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 11, 2022
• Study Start: June 1, 2022
• Primary Completion: October 18, 2023
• Study Completion: October 18, 2023
• Last Updated: February 5, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)