Metformin for the Minimization of Geographic Atrophy Progression in Patients With AMD

NCT02684578 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 15-18258
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this study is to determine whether metformin, an FDA-approved drug for the treatment of type II diabetes, is a safe and effective treatment to decrease the progression of geographic atrophy in non-diabetic patients with Age-related Macular Degeneration (AMD).

Conditions

Age-Related Macular Degeneration; Macular Degeneration, Age-Related; Dry Macular Degeneration; Geographic Atrophy

Outcome Measures

Primary Outcomes (1)

• Fundus Autofluorescence Imaging to Measure the Rate of Change in Area of Geographic Atrophy

  The primary efficacy endpoint was the annualized growth rate of the square root of geographic atrophy (GA) area in mm/year in the study eye as imaged by fundus autofluorescence (FAF) imaging. Change = (Month 18 GA Area - Baseline GA Area).

  0 months, 18 months

Secondary Outcomes (4)

• Change in Best Corrected Visual Acuity (BCVA)

  0 months, 18 months

• Change in Low-luminance Visual Acuity (LLVA)

  0 months, 18 months

• Ocular Safety as Measured by the Presence of Novel Intraocular Inflammation Judged by the Investigator to be Due to the Study Drug Metformin

  0 months, 6 months, 12 months, 18 months, 24 months

• Systemic Safety as Measured by Presence of Side Effects Listed on Metformin Drug Label as "Severe"

  0 months, 6 months, 12 months, 18 months, 24 months

Study Arms (2)

Metformin

EXPERIMENTAL

This arm will be receiving the study drug, Metformin, for the duration of the 24 month study. They will begin this drug on a low dose of Metformin, increasing the dosage in a step-wise fashion to avoid unwanted gastrointestinal discomfort, a common side effect when patients begin taking Metformin. During the 24 month study, subjects assigned to this arm will have 4 follow-up exams after the initial enrollment exam, at 6 month intervals.

Drug: Metformin

Observe

NO INTERVENTION

This arm will maintain standard of care for dry AMD, which is observation. During the 24 month study, subjects assigned to this arm will have 4 follow-up exams after the initial enrollment exam, at 6 month intervals.

Interventions

Metformin DRUG

Also known as: Glucophage

Metformin

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be \>/= 55 years of age
• Subject must have evidence of advanced dry AMD, defined by the characteristic presence of drusen and/or pigmentary changes as well as geographic atrophy
• Subject must have clear ocular media and adequate pupillary dilation
• Subject must be able to swallow capsules
• Study eye must have best corrected visual acuity (BCVA) of 20/20-20/400
• Subject must be willing and able to pay for monthly prescription of Metformin HCl for 18 months in the event that their insurance carrier will not cover the cost of the drug

You may not qualify if:

• Subjects with insufficient baseline size of geographic atrophy, less than 1.25 mm2 (0.5 Macular Photocoagulation Study Disc Areas). GA is defined as one or more well-defined and often circular patches of partial or complete depigmentation of the RPE, typically with exposure of underlying choroidal blood vessels. Even if much of the RPE appears to be preserved and large choroidal vessels are not visible, a round patch of RPE partial depigmentation may be classified as early GA. The GA in the study eye must be able to be photographed in its entirety, and it must not be contiguous with any areas of peripapillary atrophy, which can complicate area measurements.
• Subjects who are already taking metformin for another purpose
• Subjects with type 1 or 2 diabetes
• Subjects with compromised kidney function:
• Serum creatinine ≥1.5 mg/dL for males and ≥1.4 mg/dL for females
• Subjects with moderate to severe heart failure (Class III or IV, New York Heart Association Functional Classifications)
• Subjects with Child's class C cirrhosis
• Evidence of retinal atrophy due to causes other than atrophic AMD.
• Subjects who have had anti-VEGF injections or active choroidal neovascularization in the study eye during the last 12 months
• Current evidence or history of ocular disorders in the study eye that in the opinion of the investigator confounds study outcome measures, including (but not limited to):
• Non-proliferative diabetic retinopathy involving 10 or more hemorrhages or microaneurysms, or active proliferative diabetic retinopathy
• Branch or central retinal vein or artery occlusion
• Macular hole
• Pathologic myopia
• Uveitis

Sponsors & Collaborators

• University of California, San Francisco: lead
• San Francisco Veterans Affairs Medical Center: collaborator
• VA Palo Alto Health Care System: collaborator
• University of California, Davis: collaborator
• University of California, San Diego: collaborator
• Northwestern University: collaborator
• University of Illinois at Chicago: collaborator
• Retinal Consultants Medical Group: collaborator
• Retina Health Center: collaborator
• California Retina Consultants: collaborator
• Oregon Health and Science University: collaborator

Study Sites (12)

University of California, Davis

Davis, California, 95616, United States

Location

Palo Alto Veteran Affairs Medical Center

Palo Alto, California, 94304, United States

Location

Retinal Consultants Medical Group

Sacramento, California, 95819, United States

Location

San Francisco Veteran Affairs Medical Center

San Francisco, California, 94121, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

California Retina Consultants

Santa Maria, California, 93454, United States

Location

North Bay Vitreoretinal Consultants

Santa Rosa, California, 95403, United States

Location

Retina Health Center

Fort Myers, Florida, 33907, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Austin Retina Associates

Austin, Texas, 78705, United States

Location

MeSH Terms

Conditions

Macular Degeneration; Geographic Atrophy

Interventions

Metformin

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Dr. Jay Stewart
• Organization: University of California, San Francisco

jay.stewart@ucsf.edu

628-206-3123

Study Officials

• Jay M Stewart, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2016
• First Posted: February 18, 2016
• Study Start: April 1, 2016
• Primary Completion: April 1, 2022
• Study Completion: October 1, 2022
• Last Updated: June 9, 2023
• Results First Posted: June 9, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)