Metformin as a Neuroprotective Therapy for Glaucoma

Sponsor
Christopher Kai Shun Leung
Study ID
NCT05426044
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

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.
  • 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.

Study Details

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.

Key Dates

First listed
Jun 21, 2022
Start date
Jun 1, 2025
Status verified
Nov 2025
Primary completion
Dec 31, 2027
Completion
Dec 31, 2027

Study Design

Enrollment
125 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Metformin
    Oral administration
  • Placebo Comparator: Placebo

Primary Outcome Measure

Rates of RNFL/GCIPL thinning (Evaluation of Neuroprotection) [ Time Frame: 24 months ]

Central Contacts

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