Clinical trial NCT02684578: Metformin for the Minimization of Geographic Atrophy Progression in Patients With AMD
Official title: METforMIN: Metformin Administration for the Minimization of Geographic Atrophy Progression in Patients With Age-related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Age-Related Macular Degeneration
Macular Degeneration, Age-Related
Dry Macular Degeneration
Geographic Atrophy
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: San Francisco Veterans Affairs Medical Center
name: VA Palo Alto Health Care System
name: University of California, Davis
name: University of California, San Diego
name: Northwestern University
name: University of Illinois at Chicago
name: Retinal Consultants Medical Group
name: Retina Health Center
name: California Retina Consultants
name: Oregon Health and Science University
First posted: 2016-02-18
Enrollment: 66
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Fundus Autofluorescence Imaging to Measure the Rate of Change in Area of Geographic Atrophy
timeFrame: 0 months, 18 months
Secondary outcomes:
measure: Change in Best Corrected Visual Acuity (BCVA)
timeFrame: 0 months, 18 months
measure: Change in Low-luminance Visual Acuity (LLVA)
timeFrame: 0 months, 18 months
measure: Ocular Safety as Measured by the Presence of Novel Intraocular Inflammation Judged by the Investigator to be Due to the Study Drug Metformin
timeFrame: 0 months, 6 months, 12 months, 18 months, 24 months
measure: Systemic Safety as Measured by Presence of Side Effects Listed on Metformin Drug Label as "Severe"
timeFrame: 0 months, 6 months, 12 months, 18 months, 24 months
Other outcomes:
Locations:
city: Davis
country: United States
facility: University of California, Davis
state: California
city: Palo Alto
country: United States
facility: Palo Alto Veteran Affairs Medical Center
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group
state: California
city: San Francisco
country: United States
facility: San Francisco Veteran Affairs Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Maria
country: United States
facility: California Retina Consultants
state: California
city: Santa Rosa
country: United States
facility: North Bay Vitreoretinal Consultants
state: California
city: Fort Myers
country: United States
facility: Retina Health Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
Study officials:
affiliation: University of California, San Francisco
name: Jay M Stewart, MD
role: PRINCIPAL_INVESTIGATOR
References: