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Effect of Metformin on Visual Function in Patients With Glaucoma

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ClinicalTrials.gov Identifier: NCT04155164
Recruitment Status : Not yet recruiting
First Posted : November 7, 2019
Last Update Posted : November 7, 2019
Sponsor:
Information provided by (Responsible Party):
Zhongshan Ophthalmic Center, Sun Yat-sen University

Tracking Information
First Submitted Date  ICMJE November 1, 2019
First Posted Date  ICMJE November 7, 2019
Last Update Posted Date November 7, 2019
Estimated Study Start Date  ICMJE November 2019
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2019)
Visual field [ Time Frame: 0 months, 12 months ]
to measure the change in visual field loss
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2019)
  • Changes in best corrected visual acuity (BCVA) [ Time Frame: 0 months, 6 months, 12 months ]
    to measure the change in visual acuity
  • Changes in retinal RNFL thickness [ Time Frame: 0 months, 6 months, 12 months ]
    to meausre the thickness of retinal RNFL by OCT
  • Changes in retinal cup/disk ratio [ Time Frame: 0 months, 6 months, 12 months ]
    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" [ Time Frame: 0 months, 6 months, 12 months ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Metformin on Visual Function in Patients With Glaucoma
Official Title  ICMJE Effect of Metformin on Visual Function in Patients With Primary Open Angle Glaucoma: A Randomized Control Study
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes 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

Primary Purpose: Treatment
Condition  ICMJE Primary Open Angle Glaucoma
Intervention  ICMJE
  • Drug: Metformin
    Participants will receive Metformin at 1000mg for 12 months.
    Other Name: Glucophage
  • Drug: Placebos
    Placebo group will take Placebo at 1000mg for 12 months.
Study Arms  ICMJE
  • Experimental: Metformin
    Participants will receive Metformin for 12 months.
    Intervention: Drug: Metformin
  • Placebo Comparator: Placebo
    Participants will receive placebo for 12 months.
    Intervention: Drug: Placebos
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: November 4, 2019)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Xialin Liu, Prof. (020)66610720 liuxialin@gzzoc.com
Contact: Tian Zhou, Dr (020)66610720 zhoutian@gzzoc.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04155164
Other Study ID Numbers  ICMJE 2019KYPJ130
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Zhongshan Ophthalmic Center, Sun Yat-sen University
Study Sponsor  ICMJE Zhongshan Ophthalmic Center, Sun Yat-sen University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Xialin Liu, Prof. Zhongshan Ophthalmic Center, Sun Yat-sen University
Principal Investigator: Xing Liu, Prof. Zhongshan Ophthalmic Center, Sun Yat-sen University
PRS Account Zhongshan Ophthalmic Center, Sun Yat-sen University
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP