GlaucomaPhase 1NCT04118920
Safety of Topical Insulin Drops for Open-angle Glaucoma
A Phase 1 study testing Topical insulin (4 units), Topical insulin (20 units) and Artificial tears in people with Glaucoma, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Glaucoma
- What is being tested?
- Topical insulin (4 units), Topical insulin (20 units) and Artificial tears
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteCanada
- Study dates
- 27 Mar 2023to Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18-75 years
- Capable to provide informed consent
- Diagnosed of moderate primary open-angle glaucoma
- Moderate glaucoma is defined as:
- Vertical cup-to-disc ratio of 0.7-0.85 and (or)
- Moderate VF defect not within 10° of fixation (e.g. mean deviation (MD) from -6 to -12 dB on Humphrey Visual Field 24-2)
Show all 9Show fewer
- 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.
- Patients with non-restrictive diets (see exclusion criteria for a list of diets considered restrictive).
- Normal serum potassium level (3.5-5.0mEq/L or 3.5-5.0 mMol/L) and HbA1C (≤5.7%) at baseline.
Who cannot join
- Younger than 18 years of age or older than 75 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.)
- History of cataract surgery (complicated or uncomplicated) within 3 months of the study
- Any other intraocular surgery within 6 months of the initiation of the study
- Visual acuity of no light perception (NLP)
Show all 29Show fewer
- Unable to provide informed consent
- Unable to complete the tests and follow-ups required by the study
- Diagnosis of glucose intolerance, type 1 or 2 diabetes mellitus (HbA1C > 5.7%26)
- Diagnosis of conditions leading to baseline increased risk of hypokalemia and hypoglycemia such as:
- Chronic kidney disease (with or without dialysis)
- Cardiovascular disease, history of arrythmias
- Cirrhosis or other inflammatory liver diseases (hepatitis B and C)
- Inflammatory bowel disease
- Active or chronic infections causing potassium wasting: HIV, tuberculosis, hepatitis, and sepsis as a result of these infections
- Metabolic disorders predisposing to hypokalemia such as: renal tubular acidosis, primary hyperaldosteronism, Cushing's disease
- Potomania or other alcohol abuse
- Hyperhidrosis
- Polyuria
- Nephropathies such as tubulointerstitial diseases or tubular injuries causing salt-wasting
- Any hematologic or inflammatory conditions requiring plasmapheresis
- Any known insulin-secreting tumors
- Patients with restrictive diets
- Patients at risk of malnutrition due to disability limiting daily dietary intake of nutrients and electrolytes ("tea-and-toast diet")
- Veganism
- Medically recommended low-potassium diet (such as chronic kidney disease)
- Eating disorders with risks of malnutrition, such as anorexia nervosa and bulimia
- Use of medications predisposing a patient to the risk of hypokalemia such as high dose diuretics and laxatives
- History of hypersensitivity to insulin or any of the ingredients in the formulation
Trial locations and contacts
1 site in 1 country.
Canada1 site
Centre Hospitalier de l'Université de Montréal
Montreal, Quebec, H2X 3E4
About this study
Official title: Safety of Topical Insulin Eye Drops for the Treatment of Open-angle Glaucoma
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.
Read more
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.
Read the detailed description
Glaucoma: a major health care challenge of the 21st century
Glaucoma is a leading cause of irreversible blindness worldwide and is expected to affect 76 million people by the year 2020. In glaucoma, there is a permanent loss of retinal ganglion cells (RGCs), the long-projecting central nervous system (CNS) neurons that convey visual information from the retina to the brain via their axons. Clinically, such changes translate into a progressive damage of visual field and sometimes result in a complete loss of vision. Currently, intraocular pressure (IOP) reduction remains the sole target of proven glaucoma therapies, consisting of a wide range of eye drops, systemic medications, laser procedures and incisional surgeries. However, many patients continue to lose vision even when these therapies are implemented, exemplifying the unmet need for novel therapies that sustain RGC survival and stimulate their regeneration.
Dendrite pathology: an early sign of neuronal damage in glaucoma Dendrites are specialized processes that determine how neurons receive and integrate information within neuronal circuits. Dendrite retraction and synapse disassembly are early signs of pathology in several psychiatric and neurodegenerative disorders. Dendritic pathology occurs prior to soma or axon loss and correlates with substantial functional deficits. In mammals, CNS neurons have a limited capacity to regenerate after injury. While a large number of studies have focused on axonal regeneration, the ability of mammalian neurons to regrow dendrites and reestablish functional synapses has been largely ignored. This is a critical issue because pathological disconnection from pre-synaptic targets leads to persistent functional impairment and accrued neuronal death, contributing to vision loss in glaucoma.
The role of insulin in dendrite regeneration Aberrant or insufficient insulin signaling, even in the absence of diabetes, has been associated with neurodegeneration in diseases characterized by dendritic pathology, notably Alzheimer's and Parkinson's disease, as well as glaucoma. Traditionally viewed solely as a peripherally acting hormone, insulin crosses the blood-brain-barrier readily and can influence a number of physiological brain processes including neuronal survival, neurotransmission, and cognitive performance. Using a model of optic nerve transection (axotomy), members of our team (Agostinone et al. Brain 2018) showed that insulin administered as eye drops or systemically after dendrites had retracted, promoted robust dendritic growth that restored arbor area and complexity. Remarkably, insulin rescued excitatory postsynaptic sites and light-triggered retinal responses while promoting robust cell survival. This study provides the first evidence of successful dendrite regeneration in mammalian neurons. Unpublished data (manuscript in preparation) from a mouse glaucoma model by our colleagues at the CHUM (Agostinone et al., in preparation) also showed that insulin stimulates similar dendrite regeneration after ocular hypertension damage. These results confirm that injured murine RGCs can effectively regenerate dendrites and validate insulin as a powerful strategy to restore dendritic morphology in glaucoma, providing the basis for need of further investigation of insulin use as glaucoma treatment in humans.
Currently, insulin is approved for subcutaneous or intravenous use as a treatment for diabetes mellitus. Adverse events of systemic insulin include hypoglycemia, hypokalemia,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 mentioned briefly, if at all, in most of these studies, indicating the necessity of better characterizing the safety profile of such off-label use of insulin prior to implementing its use as neuroprotective and regenerative treatment for glaucoma.
Experimental nature of the medication / treatment:
Topical application of insulin with concentrations of 100 U/ml (Humulin R U-100, Eli Lilly Canada, St-Laurent, Quebec, Canada) and 500 U/ml (Entuzity, Eli Lilly Canada, St-Laurent, Quebec, Canada) once per day to eyes diagnosed with open angle glaucoma. Both products of insulin are approved by Health Canada for subcutaneous and intravenous use for the treatment of diabetes mellitus. The proposed route of administration and indication of insulin use in this current study are therefore of off-label nature, for which the investigators will request a non-objection letter from Health Canada.
Hypothesis of the study: Topical ocular insulin (up to 500 U/ml) at once per day dosing is safe in patients with open angle glaucoma.
Objectives: To document and to report any ocular and/or systemic adverse events associated with topical insulin eye drops.
- Conditions
- Glaucoma
- Being tested
- Topical insulin (4 units), Topical insulin (20 units), Artificial tears
- Keywords
- Topical insulin, Dendrite regeneration
- Medical subject headings
- Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Topical insulin (4 units)Drug
Also called Humulin R (100 units/mL)
N=6: 100 U/ml; 4 units of insulin per application; 40 microliters per drop
Topical insulin (20 units)Drug
Also called Entuzity (500 units/mL)
N=6: 500 U/ml; 20 units of insulin per application; 40 microliters per drop
Artificial tearsDrug
Also called Refresh Plus Artificial Tears
N=3, 40 microliters per drop
| Study group | Role | What they receive |
|---|---|---|
| Topical insulin | Experimental | Patients will receive topical insulin eye drops. Receives: Drug: Topical insulin (4 units); Drug: Topical insulin (20 units) |
| Topical artificial tears | Sham comparator | Patients will receive topical artificial tears. Receives: Drug: Artificial tears |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of hypoglycemia
Monitor blood glucose levels in patients
Measured: 6 months
Rate of hypokalemia
Monitor serum potassium levels in patients
Measured: 6 months
Rates of other reported adverse events
Monitor any adverse event in patients
Measured: 6 months
Ocular tolerability of the instilled drops
Monitor the ocular tolerability of insulin drops on patients with a visual analog scale of ocular tolerability
Measured: 6 months
Secondary outcomes (7)
Snellen chart visual acuity expressed in logMAR
Monitor visual acuity in patients
Measured: 6 months
Intraocular pressure (IOP)
Monitor IOP in patients
Measured: 6 months
Average retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness on spectral domain optical coherence tomography (SD-OCT)
Monitor RNFL and GCC thickness in patients
Measured: 6 months
Perfusion density (PD) on optical coherence tomography-angiography (OCT-A)
Monitor PD on OCT-A
Measured: 6 months
Flow index (FI) on OCT-A
Monitor FI on OCT-A
Measured: 6 months
Visual field index (VFI) on Swedish Interactive Thresholding Algorithm (SITA) 24-2 visual field
Monitor VFI on patients' visual fields
Measured: 6 months
Mean deviation (MD) and pattern standard deviation (PSD) on SITA 24-2 visual field
Monitor MD and PSD on patients' visual fields
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2019
- Study start27 Mar 2023
- Primary completion20 Aug 2024
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for GlaucomaStudies of the same condition, open and under way.
- More trials run by Centre hospitalier de l'Université de Montréal (CHUM)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single-arm prospective open-label interventional study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Qianqian Wang, MD, FRCSC, Principal investigator, Département d'ophtalmologie, Centre hospitalier de l'Université de Montréal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04118920
- Sponsor's protocol ID
- CE19.154
- Status last verified
- Aug 2024
- First submitted
- 2 Oct 2019
- Last updated
- 21 Aug 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006 Mar;90(3):262-7. doi: 10.1136/bjo.2005.081224.
PubMed 16488940Agostinone J, Di Polo A. Retinal ganglion cell dendrite pathology and synapse loss: Implications for glaucoma. Prog Brain Res. 2015;220:199-216. doi: 10.1016/bs.pbr.2015.04.012. Epub 2015 Jun 30.
PubMed 26497792Canadian Ophthalmological Society Glaucoma Clinical Practice Guideline Expert Committee; Canadian Ophthalmological Society. Canadian Ophthalmological Society evidence-based clinical practice guidelines for the management of glaucoma in the adult eye. Can J Ophthalmol. 2009;44 Suppl 1:S7-93. doi: 10.3129/cjo44s1. No abstract available. English, French.
PubMed 19492005Schwartz M, London A. Glaucoma as a neuropathy amenable to neuroprotection and immune manipulation. Prog Brain Res. 2008;173:375-84. doi: 10.1016/S0079-6123(08)01126-6.
PubMed 18929122Frankfort BJ, Khan AK, Tse DY, Chung I, Pang JJ, Yang Z, Gross RL, Wu SM. Elevated intraocular pressure causes inner retinal dysfunction before cell loss in a mouse model of experimental glaucoma. Invest Ophthalmol Vis Sci. 2013 Jan 28;54(1):762-70. doi: 10.1167/iovs.12-10581.
PubMed 23221072Pang JJ, Frankfort BJ, Gross RL, Wu SM. Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice. Proc Natl Acad Sci U S A. 2015 Feb 24;112(8):2593-8. doi: 10.1073/pnas.1419921112. Epub 2015 Feb 9.
PubMed 25675503Hilliard MA. Axonal degeneration and regeneration: a mechanistic tug-of-war. J Neurochem. 2009 Jan;108(1):23-32. doi: 10.1111/j.1471-4159.2008.05754.x. Epub 2008 Nov 15.
PubMed 19054282Kleinridders A. Deciphering Brain Insulin Receptor and Insulin-Like Growth Factor 1 Receptor Signalling. J Neuroendocrinol. 2016 Nov;28(11):10.1111/jne.12433. doi: 10.1111/jne.12433.
PubMed 27631195Ghasemi R, Haeri A, Dargahi L, Mohamed Z, Ahmadiani A. Insulin in the brain: sources, localization and functions. Mol Neurobiol. 2013 Feb;47(1):145-71. doi: 10.1007/s12035-012-8339-9. Epub 2012 Sep 7.
PubMed 22956272Agostinone J, Alarcon-Martinez L, Gamlin C, Yu WQ, Wong ROL, Di Polo A. Insulin signalling promotes dendrite and synapse regeneration and restores circuit function after axonal injury. Brain. 2018 Jul 1;141(7):1963-1980. doi: 10.1093/brain/awy142.
PubMed 29931057Bartlett JD, Turner-Henson A, Atchison JA, Woolley TW, Pillion DJ. Insulin administration to the eyes of normoglycemic human volunteers. J Ocul Pharmacol. 1994 Winter;10(4):683-90. doi: 10.1089/jop.1994.10.683.
PubMed 7714412Bartlett JD, Slusser TG, Turner-Henson A, Singh KP, Atchison JA, Pillion DJ. Toxicity of insulin administered chronically to human eye in vivo. J Ocul Pharmacol. 1994 Spring;10(1):101-7. doi: 10.1089/jop.1994.10.101.
PubMed 8207318Wang 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.
PubMed 28742619Fai 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.
PubMed 28828764Bastion 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.
PubMed 23749008
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Topical Insulin Eye Drops for the Treatment of Open-angle Glaucoma
- ClinicalTrials.gov ID
- NCT04118920
- Acronym / sponsor ID
- CE19.154
- Conditions
- Glaucoma
- Keywords
- Topical insulin, Dendrite regeneration
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- Study start
- 27 Mar 2023 (actual)
- Primary completion
- 20 Aug 2024 (actual)
- Study completion
- Dec 2024 (estimated)
- First posted
- 8 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Glaucoma: a major health care challenge of the 21st century
Glaucoma is a leading cause of irreversible blindness worldwide and is expected to affect 76 million people by the year 2020. In glaucoma, there is a permanent loss of retinal ganglion cells (RGCs), the long-projecting central nervous system (CNS) neurons that convey visual information from the retina to the brain via their axons. Clinically, such changes translate into a progressive damage of visual field and sometimes result in a complete loss of vision. Currently, intraocular pressure (IOP) reduction remains the sole target of proven glaucoma therapies, consisting of a wide range of eye drops, systemic medications, laser procedures and incisional surgeries. However, many patients continue to lose vision even when these therapies are implemented, exemplifying the unmet need for novel therapies that sustain RGC survival and stimulate their regeneration.
Dendrite pathology: an early sign of neuronal damage in glaucoma Dendrites are specialized processes that determine how neurons receive and integrate information within neuronal circuits. Dendrite retraction and synapse disassembly are early signs of pathology in several psychiatric and neurodegenerative disorders. Dendritic pathology occurs prior to soma or axon loss and correlates with substantial functional deficits. In mammals, CNS neurons have a limited capacity to regenerate after injury. While a large number of studies have focused on axonal regeneration, the ability of mammalian neurons to regrow dendrites and reestablish functional synapses has been largely ignored. This is a critical issue because pathological disconnection from pre-synaptic targets leads to persistent functional impairment and accrued neuronal death, contributing to vision loss in glaucoma.
The role of insulin in dendrite regeneration Aberrant or insufficient insulin signaling, even in the absence of diabetes, has been associated with neurodegeneration in diseases characterized by dendritic pathology, notably Alzheimer's and Parkinson's disease, as well as glaucoma. Traditionally viewed solely as a peripherally acting hormone, insulin crosses the blood-brain-barrier readily and can influence a number of physiological brain processes including neuronal survival, neurotransmission, and cognitive performance. Using a model of optic nerve transection (axotomy), members of our team (Agostinone et al. Brain 2018) showed that insulin administered as eye drops or systemically after dendrites had retracted, promoted robust dendritic growth that restored arbor area and complexity. Remarkably, insulin rescued excitatory postsynaptic sites and light-triggered retinal responses while promoting robust cell survival. This study provides the first evidence of successful dendrite regeneration in mammalian neurons. Unpublished data (manuscript in preparation) from a mouse glaucoma model by our colleagues at the CHUM (Agostinone et al., in preparation) also showed that insulin stimulates similar dendrite regeneration after ocular hypertension damage. These results confirm that injured murine RGCs can effectively regenerate dendrites and validate insulin as a powerful strategy to restore dendritic morphology in glaucoma, providing the basis for need of further investigation of insulin use as glaucoma treatment in humans.
Currently, insulin is approved for subcutaneous or intravenous use as a treatment for diabetes mellitus. Adverse events of systemic insulin include hypoglycemia, hypokalemia,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 mentioned briefly, if at all, in most of these studies, indicating the necessity of better characterizing the safety profile of such off-label use of insulin prior to implementing its use as neuroprotective and regenerative treatment for glaucoma.
Experimental nature of the medication / treatment:
Topical application of insulin with concentrations of 100 U/ml (Humulin R U-100, Eli Lilly Canada, St-Laurent, Quebec, Canada) and 500 U/ml (Entuzity, Eli Lilly Canada, St-Laurent, Quebec, Canada) once per day to eyes diagnosed with open angle glaucoma. Both products of insulin are approved by Health Canada for subcutaneous and intravenous use for the treatment of diabetes mellitus. The proposed route of administration and indication of insulin use in this current study are therefore of off-label nature, for which the investigators will request a non-objection letter from Health Canada.
Hypothesis of the study: Topical ocular insulin (up to 500 U/ml) at once per day dosing is safe in patients with open angle glaucoma.
Objectives: To document and to report any ocular and/or systemic adverse events associated with topical insulin eye drops.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Single-arm prospective open-label interventional study
| Arm | Type | Receives |
|---|---|---|
| Topical insulin | Experimental | Drug: Topical insulin (4 units), Drug: Topical insulin (20 units)Patients will receive topical insulin eye drops. |
| Topical artificial tears | Sham comparator | Drug: Artificial tearsPatients will receive topical artificial tears. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18-75 years
- Capable to provide informed consent
- Diagnosed of moderate primary open-angle glaucoma
- Moderate glaucoma is defined as:
- 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.
Key exclusion criteria (29 listed)
- Younger than 18 years of age or older than 75 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.)
- History of cataract surgery (complicated or uncomplicated) within 3 months of the study
- Any other intraocular surgery within 6 months of the initiation of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Topical insulin (4 units)Also: Humulin R (100 units/mL)N=6: 100 U/ml; 4 units of insulin per application; 40 microliters per drop | Drug | Topical insulin |
| Topical insulin (20 units)Also: Entuzity (500 units/mL)N=6: 500 U/ml; 20 units of insulin per application; 40 microliters per drop | Drug | Topical insulin |
| Artificial tearsAlso: Refresh Plus Artificial TearsN=3, 40 microliters per drop | Drug | Topical artificial tears |
Primary outcome
Rate of hypoglycemia
Time frame: 6 months
Monitor blood glucose levels in patients
Rate of hypokalemia
Time frame: 6 months
Monitor serum potassium levels in patients
Rates of other reported adverse events
Time frame: 6 months
Monitor any adverse event in patients
Ocular tolerability of the instilled drops
Time frame: 6 months
Monitor the ocular tolerability of insulin drops on patients with a visual analog scale of ocular tolerability
7 secondary outcomes
Snellen chart visual acuity expressed in logMAR
Time frame: 6 months
Intraocular pressure (IOP)
Time frame: 6 months
Average retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness on spectral domain optical coherence tomography (SD-OCT)
Time frame: 6 months
Perfusion density (PD) on optical coherence tomography-angiography (OCT-A)
Time frame: 6 months
Flow index (FI) on OCT-A
Time frame: 6 months
Visual field index (VFI) on Swedish Interactive Thresholding Algorithm (SITA) 24-2 visual field
Time frame: 6 months
Mean deviation (MD) and pattern standard deviation (PSD) on SITA 24-2 visual field
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
- Background: PubMed 16488940Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006 Mar;90(3):262-7. doi: 10.1136/bjo.2005.081224.
- Background: PubMed 26497792Agostinone J, Di Polo A. Retinal ganglion cell dendrite pathology and synapse loss: Implications for glaucoma. Prog Brain Res. 2015;220:199-216. doi: 10.1016/bs.pbr.2015.04.012. Epub 2015 Jun 30.
- Background: PubMed 19492005Canadian Ophthalmological Society Glaucoma Clinical Practice Guideline Expert Committee; Canadian Ophthalmological Society. Canadian Ophthalmological Society evidence-based clinical practice guidelines for the management of glaucoma in the adult eye. Can J Ophthalmol. 2009;44 Suppl 1:S7-93. doi: 10.3129/cjo44s1. No abstract available. English, French.
- Background: PubMed 18929122Schwartz M, London A. Glaucoma as a neuropathy amenable to neuroprotection and immune manipulation. Prog Brain Res. 2008;173:375-84. doi: 10.1016/S0079-6123(08)01126-6.
- Background: PubMed 23221072Frankfort BJ, Khan AK, Tse DY, Chung I, Pang JJ, Yang Z, Gross RL, Wu SM. Elevated intraocular pressure causes inner retinal dysfunction before cell loss in a mouse model of experimental glaucoma. Invest Ophthalmol Vis Sci. 2013 Jan 28;54(1):762-70. doi: 10.1167/iovs.12-10581.
- Background: PubMed 25675503Pang JJ, Frankfort BJ, Gross RL, Wu SM. Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice. Proc Natl Acad Sci U S A. 2015 Feb 24;112(8):2593-8. doi: 10.1073/pnas.1419921112. Epub 2015 Feb 9.
- Background: PubMed 19054282Hilliard MA. Axonal degeneration and regeneration: a mechanistic tug-of-war. J Neurochem. 2009 Jan;108(1):23-32. doi: 10.1111/j.1471-4159.2008.05754.x. Epub 2008 Nov 15.
- Background: PubMed 27631195Kleinridders A. Deciphering Brain Insulin Receptor and Insulin-Like Growth Factor 1 Receptor Signalling. J Neuroendocrinol. 2016 Nov;28(11):10.1111/jne.12433. doi: 10.1111/jne.12433.
- Background: PubMed 22956272Ghasemi R, Haeri A, Dargahi L, Mohamed Z, Ahmadiani A. Insulin in the brain: sources, localization and functions. Mol Neurobiol. 2013 Feb;47(1):145-71. doi: 10.1007/s12035-012-8339-9. Epub 2012 Sep 7.
- Background: PubMed 29931057Agostinone J, Alarcon-Martinez L, Gamlin C, Yu WQ, Wong ROL, Di Polo A. Insulin signalling promotes dendrite and synapse regeneration and restores circuit function after axonal injury. Brain. 2018 Jul 1;141(7):1963-1980. doi: 10.1093/brain/awy142.
- Background: PubMed 7714412Bartlett JD, Turner-Henson A, Atchison JA, Woolley TW, Pillion DJ. Insulin administration to the eyes of normoglycemic human volunteers. J Ocul Pharmacol. 1994 Winter;10(4):683-90. doi: 10.1089/jop.1994.10.683.
- Background: PubMed 8207318Bartlett JD, Slusser TG, Turner-Henson A, Singh KP, Atchison JA, Pillion DJ. Toxicity of insulin administered chronically to human eye in vivo. J Ocul Pharmacol. 1994 Spring;10(1):101-7. doi: 10.1089/jop.1994.10.101.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Qianqian Wang, MD, FRCSC principal investigator
Département d'ophtalmologie, Centre hospitalier de l'Université de Montréal
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Topical insulin (4 units), Topical insulin (20 units) and Artificial tears in people with Glaucoma, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of hypoglycemia (time frame: 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04118920, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2024.