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
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|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single-arm prospective open-label interventional study|
|Masking:||None (Open Label)|
|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|
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
- Rate of hypoglycemia [ Time Frame: 1 year ]Monitor blood glucose levels in patients
- Rate of hypokalemia [ Time Frame: 1 year ]Monitor serum potassium levels in patients
- Rates of other reported adverse events [ Time Frame: 1 year ]Monitor any adverse event in patients
- Snellen chart visual acuity expressed in logMAR [ Time Frame: 1 year ]Monitor visual acuity in patients
- Intraocular pressure (IOP) [ Time Frame: 1 year ]Monitor IOP in patients
- Average RNFL and GCC thickness on SD-OCT [ Time Frame: 1 year ]Monitor RNFL and GCC thickness in patients
- Mean deviation on visual field (VF) [ Time Frame: 1 year ]Monitor mean deviation on VF in patients
- PERG P50 implicit time [ Time Frame: 1 year ]Monitor P50 implicit time
- P50-N95 amplitude on PERG [ Time Frame: 1 year ]Monitor P50-N95 amplitude via PERG
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
|Centre Hospitalier de l'Université de Montréal|
|Montréal, Quebec, Canada, H2X 3E4|
|Principal Investigator:||Qianqian Wang, MD, FRCSC||Département d'ophtalmologie, Centre hospitalier de l'Université de Montréal|