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

NCT ID: NCT02684578

Last Updated: 2023-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2022-10-31

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).

Detailed Description

This is a phase II, single-blind, randomized, evaluation of the safety and efficacy of metformin use to decrease geographic atrophy (GA) progression in non-diabetic patients with dry Age-related Macular Degeneration (AMD). Approximately 186 study subjects throughout four separate study sites will be randomized in a 1:1 ratio to the treatment group and the observation group. The treatment group will be assigned to the study intervention (oral Metformin) for 18 months while the observation group will receive no intervention for 18 months, instead continuing with standard of care ophthalmic exams and close monitoring of their disease. There will be one additional follow up visit at 24 months. Throughout the 24 month study period, the progression of subjects' GA or drusen growth will be measured via ocular imaging taken at standard of care follow-up examinations, including fundus autofluorescence imaging, optical coherence tomography (OCT), and fundus photography.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Metformin

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.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Observe

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Metformin

Intervention Type: DRUG

Other Intervention Names

Glucophage

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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):

1. Non-proliferative diabetic retinopathy involving 10 or more hemorrhages or microaneurysms, or active proliferative diabetic retinopathy

2. Branch or central retinal vein or artery occlusion

3. Macular hole

4. Pathologic myopia

5. Uveitis

6. Pseudovitelliform maculopathy

7. Intraoperative surgery within the last 90 days prior to study eye enrollment

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

San Francisco Veterans Affairs Medical Center

FED

Sponsor Role: collaborator

VA Palo Alto Health Care System

FED

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: collaborator

University of Illinois at Chicago

OTHER

Sponsor Role: collaborator

Retinal Consultants Medical Group

OTHER

Sponsor Role: collaborator

Retina Health Center

INDUSTRY

Sponsor Role: collaborator

California Retina Consultants

OTHER

Sponsor Role: collaborator

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jay M Stewart, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, Davis

Davis, California, United States

Palo Alto Veteran Affairs Medical Center

Palo Alto, California, United States

Retinal Consultants Medical Group

Sacramento, California, United States

San Francisco Veteran Affairs Medical Center

San Francisco, California, United States

University of California San Francisco

San Francisco, California, United States

California Retina Consultants

Santa Maria, California, United States

North Bay Vitreoretinal Consultants

Santa Rosa, California, United States

Retina Health Center

Fort Myers, Florida, United States

Northwestern University

Chicago, Illinois, United States

University of Illinois at Chicago

Chicago, Illinois, United States

Oregon Health and Science University

Portland, Oregon, United States

Austin Retina Associates

Austin, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

15-18258

Identifier Type: -

Identifier Source: org_study_id