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Safety of Topical Insulin Drops for Open-angle Glaucoma

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ClinicalTrials.gov Identifier: NCT04118920
Recruitment Status : Suspended (Pending regulatory authority clearance)
First Posted : October 8, 2019
Last Update Posted : August 20, 2021
Sponsor:
Information provided by (Responsible Party):
Centre hospitalier de l'Université de Montréal (CHUM)

Brief Summary:

Glaucoma, a leading cause of irreversible blindness worldwide, is characterized by a permanent loss of retinal ganglion cells (RGCs), a group of central nervous system (CNS) neurons that convey visual information from the retina to the brain via their long axons. Clinically, axonal damage in RGC results in a loss of visual field and may lead to blindness. Currently, reducing eye pressure remains the sole target of proven glaucoma therapies. However, many patients continue to lose vision even when standard interventions are implemented, accentuating the unmet need for novel therapies.

Dendrites are processes that determine how neurons receive and integrate information. Dendrite retraction and synapse breakdown are early signs of several neurodegenerative disorders. In mammals, CNS neurons have an extremely limited capacity to regenerate after injury. To date, the ability of mammalian neurons to regrow dendrites and reestablish functional synapses has been largely ignored.

Insufficient insulin signaling has been implicated in diseases characterized by dendritic pathology, notably Alzheimer's disease and glaucoma. A versatile hormone, insulin readily crosses the blood-brain-barrier and influences numerous brain processes. In a mouse model of optic nerve transection, our team showed that insulin administration after optic nerve injury promoted robust dendritic regrowth, RGCs survival and retinal responses rescue, providing the first evidence of successful dendrite regeneration in mammalian neurons. Our research validates insulin as a powerful medication to restore dendritic function in glaucoma, forming the basis for using insulin as glaucoma treatment in humans.

Currently, insulin is approved for diabetes. Adverse events of systemic insulin include hypoglycemia, hypokalemia, lipodystrophy, allergies, weight gain, peripheral edema and drug interactions. Experimental use of ocular topical insulin have been tested in small cohorts of healthy individuals and diabetic patients, reporting no significant adverse events. However, these protocols varied in insulin posology and adverse events were only touched upon briefly, indicating the necessity to better characterize the safety profile of such off-label use of insulin before its application as a neuroprotective and regenerative treatment for glaucoma.

In this study, the investigators hypothesize that topical ocular insulin (up to 500 U/ml) at once per day dosing is safe in patients with open angle glaucoma.


Condition or disease Intervention/treatment Phase
Glaucoma Drug: Topic insulin (4 units) Drug: Topic insulin (20 units) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single-arm prospective open-label interventional study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety of Topical Insulin Eye Drops for the Treatment of Open-angle Glaucoma
Estimated Study Start Date : January 2022
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Glaucoma

Arm Intervention/treatment
Experimental: Topical insulin
Patients will receive topical insulin eye drops.
Drug: Topic insulin (4 units)
N=6: 100 U/ml; 4 units of insulin per application; 40 microliters per drop

Drug: Topic insulin (20 units)
N=6: 500 U/ml; 20 units of insulin per application; 40 microliters per drop




Primary Outcome Measures :
  1. Rate of hypoglycemia [ Time Frame: 1 year ]
    Monitor blood glucose levels in patients

  2. Rate of hypokalemia [ Time Frame: 1 year ]
    Monitor serum potassium levels in patients

  3. Rates of other reported adverse events [ Time Frame: 1 year ]
    Monitor any adverse event in patients


Secondary Outcome Measures :
  1. Snellen chart visual acuity expressed in logMAR [ Time Frame: 1 year ]
    Monitor visual acuity in patients

  2. Intraocular pressure (IOP) [ Time Frame: 1 year ]
    Monitor IOP in patients

  3. Average RNFL and GCC thickness on SD-OCT [ Time Frame: 1 year ]
    Monitor RNFL and GCC thickness in patients

  4. Mean deviation on visual field (VF) [ Time Frame: 1 year ]
    Monitor mean deviation on VF in patients

  5. PERG P50 implicit time [ Time Frame: 1 year ]
    Monitor P50 implicit time

  6. P50-N95 amplitude on PERG [ Time Frame: 1 year ]
    Monitor P50-N95 amplitude via PERG



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

* Please note that this study is only open to patients who are Quebec residents and who are already followed at the Centre Hospitalier de l'Université de Montréal (CHUM).

Inclusion Criteria:

  • Age of 18 years or older
  • Capable to provide informed consent
  • Diagnosed of terminal open angle glaucoma (visual acuity ≤ 20/200 and / or visual field of 20 degrees or less)
  • Only one eye per patient will be selected as the study eye - if both eyes meet the inclusion criteria, the eye with the worse acuity and /or visual field will be selected. The contralateral eye will be left untouched.

Exclusion Criteria:

  • Younger than 18 years of age
  • Pregnant or breastfeeding woman
  • Presence of any ocular pathologies other than glaucoma that contributes to the severe vision loss (retinopathy / maculopathy, non-glaucomatous optic neuropathy, severe uveitis, keratopathy, etc.)
  • Diagnosis of glucose intolerance, type 1 or 2 diabetes mellitus (HbA1C > 5.7%)
  • Visual acuity of no light perception (NLP)
  • Unable to provide informed consent
  • Unable to complete the tests and follow-ups required by the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04118920


Locations
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Canada, Quebec
Centre Hospitalier de l'Université de Montréal
Montréal, Quebec, Canada, H2X 3E4
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
Investigators
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Principal Investigator: Qianqian Wang, MD, FRCSC Département d'ophtalmologie, Centre hospitalier de l'Université de Montréal
Publications:
SA J. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics. 2005;4(4):287-91.
Information for the Physician: Humulin R Regular Insulin Human Injection, USP, (rDNA origin) 100 units per ml (U-100). In: Administration FaD, editor.: Lilly USA; 2011.

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Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier: NCT04118920    
Other Study ID Numbers: CE19.154
First Posted: October 8, 2019    Key Record Dates
Last Update Posted: August 20, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Centre hospitalier de l'Université de Montréal (CHUM):
Topical insulin
Dendrite regeneration
Additional relevant MeSH terms:
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Glaucoma
Glaucoma, Open-Angle
Ocular Hypertension
Eye Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs