Metformin as a Neuroprotective Therapy for Glaucoma

NCT05426044 | Recruiting Phase 2

• 1 other identifier: UW 21-586
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

Brief Summary

Glaucoma, a chronic degenerative disease of the optic nerve, is the leading cause of irreversible blindness worldwide. Although lowering the intraocular pressure (IOP) has been shown to be effective to slow optic nerve degeneration, a significant portion of glaucoma patients continue to develop progressive loss in vision despite adequate control of IOP. Development of neuroprotective therapy to prevent optic nerve degeneration by mechanisms other than IOP- lowering is critical to reduce the burden of glaucoma blindness. With 76 million glaucoma patients in 2020 worldwide, the need to investigate neuroprotection for glaucoma is pressing. While metformin is a widely adopted oral hypoglycemic medication for treatment of type 2 diabetes mellitus (DM), increasing evidence from clinical studies has shown that metformin can decrease the risk of many age-related diseases including neurodegenerative diseases. In a retrospective study of 150,016 patients with DM, those taking metformin at \>1500mg/day had a 25% reduced risk of development of open-angle glaucoma than those who took no metformin. Metformin has a high safety profile. The investigators aim to investigate whether metformin can be repurposed to a neuroprotective therapy for glaucoma patients in a randomized controlled trial. The investigators propose to conduct a 24-month, double-blind, placebo-controlled, parallel group, randomizing 125 primary open angle glaucoma patients who have progressive retinal nerve fiber layer (RNFL) and/or ganglion cell inner plexiform layer (GCIPL) thinning in at least one eye, as determined by optical coherence tomography Trend-based Progression Analysis (TPA) or Guided Progression Analysis (GPA), to receive metformin 1500mg/day or placebo. All patients will be followed up at 2-month intervals for IOP, RNFL thickness, and visual field (VF) measurements. The objectives are to compare (1) the rates of change of average RNFL thickness (primary outcome measure), and (2) the rates of change of VF mean deviation (MD) (secondary outcome measure) between treatment groups. The investigators hypothesize that patients treated with metformin have a slower rate of RNFL thinning, and a slower rate of VF MD decline compared with those treated with placebo at similar levels of IOP over the 24-month follow-up. The proposed study has the potential to mark a paradigm shift in the management of glaucoma patients by demonstrating that neuroprotection is attainable with metformin, which will alleviate the increasing burden of glaucoma blindness in China and other Asian countries where glaucoma patients with normal levels of IOP are prevalent. Furthermore, it will inform and impact the study design in future neuroprotection trials which can expedite the development of neuroprotective therapy for glaucoma.

Conditions

Glaucoma

Keywords

Metformin; Neuroprotection; Neuroenhancement

Outcome Measures

Primary Outcomes (2)

• Rates of RNFL/GCIPL thinning (Evaluation of Neuroprotection)

  For evaluation of neuroprotection, the rates of RNFL thinning between the metformin-treated group and the placebo-treated group will be compared using a linear mixed model after adjusting for clustering between fellow eyes and covariates (i.e. signal strength, baseline RNFL thickness, IOP during follow-up, age, and axial length) will be exported for the analysis.

  24 months

• Change in visual field sensitivity (Evaluation of Neuroenhancement)

  For evaluation of neuroenhancement, the change in VF sensitivity between baseline and one month will be determined from each treatment group using linear mixed modeling, after adjusting for clustering between fellow eyes and covariates. Only eyes with progressive RNFL/GCIPL thinning by TPA or GPA at the baseline will be included in the analysis.

  4 weeks

Secondary Outcomes (1)

• Rates of change of VF MD and VFI

  24 months

Other Outcomes (1)

• Risk factors associated with the rates of RNFL thinning and VF MD/VFI decline

  24 months

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Oral administration

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Metformin DRUG

Patients randomized to metformin treatment will take 750 mg Metformin Hydrochloride tablets once daily for 4 weeks; the dose will be increased to 750 mg twice daily for the rest of the study period.

Metformin

Placebo DRUG

Patients randomized to placebo group treatment will take identical-appearing placebo tablets once daily for 4 weeks; and twice daily for the rest of the study period.

Placebo

Eligibility Criteria

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

You may qualify if:

• age ≥18 years
• best corrected VA ≥20/40
• IOP ≤24mmHg at the screening and baseline visits
• progressive RNFL and/or GCIPL thinning by TPA or GPA over the past 3 years in at least one eye.

You may not qualify if:

• patients with DM, kidney or liver diseases
• pathological myopia
• cognitive impairment (e.g. Alzheimer's disease)
• diseases that may cause visual field loss or optic disc abnormalities other than glaucoma
• inability to perform reliable visual field
• suboptimal quality of OCT images.

Sponsors & Collaborators

• Christopher Kai Shun Leung: lead

Study Sites (1)

HKU Eye Centre

Wong Chuk Hang, Hong Kong

RECRUITING

MeSH Terms

Conditions

Glaucoma

Interventions

Metformin

Condition Hierarchy (Ancestors)

Ocular Hypertension; Eye Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Christopher LEUNG, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christopher LEUNG, MD

CONTACT

(852)3962-1405; cleung21@hku.hk

Nate CHAN

CONTACT

(852)3910-3906; natechan@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chairperson and Clinical Professor

Study Record Dates

• First Submitted: June 15, 2022
• First Posted: June 21, 2022
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)