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

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ClinicalTrials.gov Identifier: NCT02684578
Recruitment Status : Recruiting
First Posted : February 18, 2016
Last Update Posted : January 29, 2019
Sponsor:
Collaborators:
San Francisco Veterans Affairs Medical Center
VA Palo Alto Health Care System
University of California, Davis
University of California, Los Angeles
University of California, Irvine
University of California, San Diego
Northwestern University
University of Illinois at Chicago
Retinal Consultants Medical Group
Retina Health Center
California Retina Consultants
Oregon Health and Science University
Information provided by (Responsible Party):
University of California, San Francisco

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).

Condition or disease Intervention/treatment Phase
Age-Related Macular Degeneration Macular Degeneration, Age-Related Dry Macular Degeneration Geographic Atrophy Drug: Metformin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 186 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: METforMIN: Metformin Administration for the Minimization of Geographic Atrophy Progression in Patients With Age-related Macular Degeneration
Study Start Date : April 2016
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Metformin
This arm will be receiving the study drug, Metformin, for the duration of the 18 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 18 month study, subjects assigned to this arm will have 3 follow-up exams after the initial enrollment exam, at 6 month intervals.
Drug: Metformin
Other Name: Glucophage

No Intervention: Observe
This arm will maintain standard of care for dry AMD, which is observation. During the 18 month study, subjects assigned to this arm will have 3 follow-up exams after the initial enrollment exam, at 6 month intervals.



Primary Outcome Measures :
  1. Fundus autoflorescence imaging to measure the rate of change in area of geographic atrophy or drusen growth [ Time Frame: 0 months, 6 months, 12 months, 18 months, 24 months ]

Secondary Outcome Measures :
  1. Changes in best corrected visual acuity (BCVA) [ Time Frame: 0 months, 6 months, 12 months, 18 months, 24 months ]
  2. Changes in normal luminance minus low-luminance visual acuity [ Time Frame: 0 months, 6 months, 12 months, 18 months, 24 months ]
    This measure has been shown to correlate well with enlargement of GA

  3. Changes in scores over the study period on the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) [ Time Frame: 0 months, 18 months ]
    The changes in patients' scores from time of enrollment to final follow-up exam will be compared between the two study arms

  4. Ocular safety as measured by the presence of novel intraocular inflammation judged by the investigator to be due to the study drug metformin [ Time Frame: 0 months, 6 months, 12 months, 18 months, 24 months ]
    Subjects assigned to the Metformin study arm will be assessed at each follow-up eye exam to confirm ocular safety of metformin. The Data Safety and Management Board for this study will also assess the safety of metformin at different time points throughout the study. They will formally meet to discuss study subject safety at 25% enrollment and 75% enrollment. The potential for ocular side effects due to metformin is thought to be very low, due to the large number of diabetic patients who take this drug and are followed closely for diabetic retinopathy or other ocular disease.

  5. Systemic safety as measured by presence of side effects listed on Metformin drug label as "severe" [ Time Frame: 0 months, 6 months, 12 months, 18 months, 24 months ]

    These include:

    Infrequent side effects of metformin (severe):

    • Trouble Breathing

    Rare side effects of metformin (severe):

    • Increased Blood Acidity due to High Levels of Lactic Acid (Lactic acidosis)
    • Low Blood Sugar
    • Megaloblastic Anemia
    • Reaction due to an Allergy

    Subjects assigned to the Metformin study arm will be assessed for these side-effects at each follow-up eye exam to confirm ocular safety of metformin. The Data Safety and Management Board for this study will also assess the safety of metformin at different time points throughout the study. They will formally meet to discuss study subject safety at 25% enrollment and 75% enrollment.




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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02684578


Contacts
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Contact: Jay M Stewart, MD 415-206-3123 eyestudy@ucsf.edu

Locations
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United States, California
University of California, Davis Recruiting
Davis, California, United States, 95616
Contact: Angela Beliveau, MPH    916-734-6814      
University of California, Irvine Recruiting
Irvine, California, United States, 92697
Contact: Rosie Magallon    949-824-8297      
Palo Alto Veteran Affairs Medical Center Recruiting
Palo Alto, California, United States, 94304
Contact: Lo-Shan Leung, MD    650-493-5000 ext 11-65751      
Retinal Consultants Medical Group Recruiting
Sacramento, California, United States, 95819
Contact: Whitney Lewis    916-453-5429      
San Francisco Veteran Affairs Medical Center Recruiting
San Francisco, California, United States, 94121
Contact: Melissa Neuwelt, MD    415-206-3123      
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Catherine Psaras, BA    415-206-3123    eyestudy@ucsf.edu   
Principal Investigator: Jay M Stewart, MD         
California Retina Consultants Recruiting
Santa Maria, California, United States, 93454
Contact: Tammy Lauinger    805-922-2068      
North Bay Vitreoretinal Consultants Recruiting
Santa Rosa, California, United States, 95403
Contact: Thomas Schlesinger, MD PhD    707-575-5353      
United States, Florida
Retina Health Center Recruiting
Fort Myers, Florida, United States, 33907
Contact: Wendy Nelson    239-337-3337 ext 213      
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Nikki Seddon    312-695-0252      
University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60612
Contact: Jie Sun    312-355-1862      
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Jennifer Maykoski    503-494-3064      
Contact: Shelley Hanel    503-494-1986      
United States, Texas
Austin Retina Associates Recruiting
Austin, Texas, United States, 78705
Contact: Gopal Karsaliya    877-925-7649      
Sponsors and Collaborators
University of California, San Francisco
San Francisco Veterans Affairs Medical Center
VA Palo Alto Health Care System
University of California, Davis
University of California, Los Angeles
University of California, Irvine
University of California, San Diego
Northwestern University
University of Illinois at Chicago
Retinal Consultants Medical Group
Retina Health Center
California Retina Consultants
Oregon Health and Science University
Investigators
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Principal Investigator: Jay M Stewart, MD University of California, San Francisco

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02684578     History of Changes
Other Study ID Numbers: 15-18258
First Posted: February 18, 2016    Key Record Dates
Last Update Posted: January 29, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Macular Degeneration
Geographic Atrophy
Atrophy
Retinal Degeneration
Retinal Diseases
Eye Diseases
Pathological Conditions, Anatomical
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs