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Effect of Metformin on Visual Function in Patients With Glaucoma

Primary Purpose

Primary Open Angle Glaucoma

Status

Recruiting

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

Metformin

Placebos

About this trial

This is an interventional treatment trial for Primary Open Angle Glaucoma focused on measuring Primary Open Angle Glaucoma, Metformin, Visual function

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age between 18-65 years old;
The baseline value of intraocular pressure ≤ 21 mmHg in either eye whether untreated or treated by ≤ 2 eye drops (laser or filtering surgery should be performed over 3 months).
Over two times of experience of visual field examination (24-2 or 30-2 visual field examinations) in the past two years, or false positive/false negative ratio less than 33%;
Diagnosed POAG by Glaucoma specialists from Zhongshan Ophthalmic Center with open angle, and impairment in optic disc or visual field in one or both eyes.
Patient is at risk of glaucomatous progression, as determined by the documented presence of optic disc hemorrhage within 12 months in either eye, OR ≥2 of the following risk factors:
Vertical cup-to-disc ratio >0.8 in one or both eyes
Mean deviation in visual field worse than <10 dB in either eye (verified by the reading center)
Pseudoexfoliation in either eye
Family history (parent or sibling) of glaucoma
Hypertension
Systemic hypertension requiring medical treatment Migraine (defined by the International Headache Society with or without aura, Raynaud's syndrome, or both:
The main organs are functioning normally and meet the following criteria:
1. Blood sample should meet the following criteria: (no blood transfusion within 14 days) A. Hemoglobin (> 90g/L); B. Platelet count (>105*10e9/L)
2. Biochemical and urinary examinations should meet the following criteria:
1. . Urine bilirubin < 1.25 times ULN (Upper Limit of Normal);
2. . ALT and AST < 2.5 times ULN;
3. . CREA ≤ ULN;

Exclusion criteria:

Secondary open-angle glaucoma (such as pigmentation syndrome, trauma, etc.) or angle-closure glaucoma.
The best corrected visual acuity of either eye is less than 6/36;
The mean derivation of visual field in either eye is less than - 22dB.
Use of >2 topical (or any oral) IOP-lowering products at the baseline visit.
Any ocular pathology in either eye that may have interfered with the ability to obtain visual field, disc imaging, or accurate IOP readings such as uveitis, refractive opacification;
Eye drops such as neuroprotective therapies have been used in the past three weeks might affect this clinical study, for inclusion need 8 weeks of wash period.
Pregnant or nursing women;
Diabetes mellitus, definite impairment of liver and kidney function, or severe heart, liver or kidney diseases;
In the last three months, ophthalmic surgery (including cataract surgery) has been performed
Enrolled in other clinical study at the same time.
Could not complete the study according to the requirements in this research .
History of epilepsy or severe mental illness, including schizophrenia, bipolar disorder or severe depression

Sites / Locations

Zhongshan Ophthalmic CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Metformin

Placebo

Arm Description

Participants will receive Metformin for 12 months.

Participants will receive placebo for 12 months.

Outcomes

Primary Outcome Measures

Visual field

to measure the change in visual field loss

Secondary Outcome Measures

Changes in best corrected visual acuity (BCVA)

to measure the change in visual acuity

Changes in retinal RNFL thickness

to meausre the thickness of retinal RNFL by OCT

Changes in retinal cup/disk ratio

to measure the alterations in retina cup/disk ratio

Systemic safety as measured by presence of side effects listed on Metformin drug label as "severe"

These include: Infrequent side effects of Metformin (severe):Dyspnea; Rare side effects of Metformin (severe):Lactic acidosis; Hypoglycemia; Megaloblastic Anemia; Allergic reactions. The participants will be assessed for these side-effects at each follow-up ocular exam to confirm ocular and systematic safety of Metformin. Blood samples will be collected at 0 month, 6 months, and 12 months to value AMPK, methylation level and inflammatory responses. The Data Monitoring Committee for this study will also assess the safety of Metformin at different time points throughout the study.

Full Information

NCT ID

NCT04155164

First Posted

November 1, 2019

Last Updated

February 10, 2022

Sponsor

Zhongshan Ophthalmic Center, Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT04155164

Brief Title

Effect of Metformin on Visual Function in Patients With Glaucoma

Official Title

Effect of Metformin on Visual Function in Patients With Primary Open Angle Glaucoma: A Randomized Control Study

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Recruiting

Study Start Date

December 10, 2019 (Actual)

Primary Completion Date

May 2022 (Anticipated)

Study Completion Date

May 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Zhongshan Ophthalmic Center, Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to determine whether Metformin could prevent the progression of glaucoma in a safe and effective manner.

Detailed Description

Primary open-angle glaucoma (POAG) is a serious blinding disease characterized by irreversible damage to retinal ganglion cells (RGCs). At present, there is no effective treatment for the rescue of visual function loss caused by POAG. Metformin is the classic first-line therapy for diabetes. Recently, it has been found that Metformin may have other beneficial effects such as promoting weight loss and reversing age-related neurodegeneration. Importantly, retrospective case-control studies found that there were associations between Metformin treatment and a reduction in the incidence of glaucoma. Specifically, diabetic patients treated by Metformin had a 25% lower risk to develop open-angle glaucoma. In addition, previous animal experiments have preliminarily shown that Metformin can play a neuroprotective role by activating AMPK kinase, regulating methylation levels and promoting ganglion cell survival. Therefore, the investigators hypothesize that Metformin can prevent visual function deterioration via rescuing retinal ganglion cells. The main objective of this study is to assess the progression of visual field loss in patients with POAG after treatment with Metformin versus placebo. The secondary objectives include the followings: RNFL thickness, vision, cup/disk ratio, safety, and biochemical tests to determine the alteration of AMPK and methylation parameters associated to the use of Metformin. Approximately 40 study subjects will be randomized in a 1:1 ratio to each treatment group. The treatment group will be assigned to the study intervention (oral Metformin) for 12 months while the placebo group will receive placebo containing fructose and starch for 12 months. Throughout the 12-month study period, progression of visual function and systematic safety examinations will be measured. At 18 months, there will be one additional follow up visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Open Angle Glaucoma

Keywords

Primary Open Angle Glaucoma, Metformin, Visual function

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Participants and researchers are double-blind. After signing informed consent, subjects who meet the inclusion criteria will be randomly divided into the oral Metformin experimental group or the oral placebo control group at a ratio of 1:1. Random lists will be generated by independent statisticians. Randomized group will be sealed in a separate opaque envelope, showing only the research identification number. Participants and researchers (medical evaluators, outcome evaluators and data analysts) will be unaware of the grouping. During the period of treatment, if patient suffers from lactic acidosis, excessive ventilation, myalgia, the masking should be unveiled and his/her systematic and eye conditions should be assessed to choose the best treatment. The choice of remedial treatment plan is based on the consensus of doctors and patients. The changes of treatment methods and curative effect should be recorded in detail for future analysis

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Metformin

Arm Type

Experimental

Arm Description

Participants will receive Metformin for 12 months.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will receive placebo for 12 months.

Intervention Type

Drug

Intervention Name(s)

Metformin

Other Intervention Name(s)

Glucophage

Intervention Description

Participants will receive Metformin at 1000mg for 12 months.

Intervention Type

Drug

Intervention Name(s)

Placebos

Intervention Description

Placebo group will take Placebo at 1000mg for 12 months.

Primary Outcome Measure Information:

Title

Visual field

Description

to measure the change in visual field loss

Time Frame

0 months, 12 months

Secondary Outcome Measure Information:

Title

Changes in best corrected visual acuity (BCVA)

Description

to measure the change in visual acuity

Time Frame

0 months, 6 months, 12 months

Title

Changes in retinal RNFL thickness

Description

to meausre the thickness of retinal RNFL by OCT

Time Frame

0 months, 6 months, 12 months

Title

Changes in retinal cup/disk ratio

Description

to measure the alterations in retina cup/disk ratio

Time Frame

0 months, 6 months, 12 months

Title

Systemic safety as measured by presence of side effects listed on Metformin drug label as "severe"

Description

Time Frame

0 months, 6 months, 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age between 18-65 years old; The baseline value of intraocular pressure ≤ 21 mmHg in either eye whether untreated or treated by ≤ 2 eye drops (laser or filtering surgery should be performed over 3 months). Over two times of experience of visual field examination (24-2 or 30-2 visual field examinations) in the past two years, or false positive/false negative ratio less than 33%; Diagnosed POAG by Glaucoma specialists from Zhongshan Ophthalmic Center with open angle, and impairment in optic disc or visual field in one or both eyes. Patient is at risk of glaucomatous progression, as determined by the documented presence of optic disc hemorrhage within 12 months in either eye, OR ≥2 of the following risk factors: Vertical cup-to-disc ratio >0.8 in one or both eyes Mean deviation in visual field worse than <10 dB in either eye (verified by the reading center) Pseudoexfoliation in either eye Family history (parent or sibling) of glaucoma Hypertension Systemic hypertension requiring medical treatment Migraine (defined by the International Headache Society with or without aura, Raynaud's syndrome, or both: The main organs are functioning normally and meet the following criteria: Blood sample should meet the following criteria: (no blood transfusion within 14 days) A. Hemoglobin (> 90g/L); B. Platelet count (>105*10e9/L) Biochemical and urinary examinations should meet the following criteria: . Urine bilirubin < 1.25 times ULN (Upper Limit of Normal); . ALT and AST < 2.5 times ULN; . CREA ≤ ULN; Exclusion criteria: Secondary open-angle glaucoma (such as pigmentation syndrome, trauma, etc.) or angle-closure glaucoma. The best corrected visual acuity of either eye is less than 6/36; The mean derivation of visual field in either eye is less than - 22dB. Use of >2 topical (or any oral) IOP-lowering products at the baseline visit. Any ocular pathology in either eye that may have interfered with the ability to obtain visual field, disc imaging, or accurate IOP readings such as uveitis, refractive opacification; Eye drops such as neuroprotective therapies have been used in the past three weeks might affect this clinical study, for inclusion need 8 weeks of wash period. Pregnant or nursing women; Diabetes mellitus, definite impairment of liver and kidney function, or severe heart, liver or kidney diseases; In the last three months, ophthalmic surgery (including cataract surgery) has been performed Enrolled in other clinical study at the same time. Could not complete the study according to the requirements in this research . History of epilepsy or severe mental illness, including schizophrenia, bipolar disorder or severe depression

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Xialin Liu, Prof.

Phone

(020)66610720

liuxialin@gzzoc.com

First Name & Middle Initial & Last Name or Official Title & Degree

Tian Zhou, Dr

Phone

(020)66610720

zhoutian@gzzoc.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xialin Liu, Prof.

Organizational Affiliation

Zhongshan Ophthalmic Center, Sun Yat-sen University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Xing Liu, Prof.

Organizational Affiliation

Zhongshan Ophthalmic Center, Sun Yat-sen University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Zhongshan Ophthalmic Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tian Zhou, phD

zhoutian@gzzoc.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Effect of Metformin on Visual Function in Patients With Glaucoma

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