Trial Outcomes & Findings for Metformin for the Minimization of Geographic Atrophy Progression in Patients With AMD (NCT NCT02684578)
NCT ID: NCT02684578
Last Updated: 2023-06-09
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
66 participants
Primary outcome timeframe
0 months, 18 months
Results posted on
2023-06-09
Participant Flow
Unit of analysis: eyes
Participant milestones
| Measure |
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.
Metformin
|
Observation
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.
|
|---|---|---|
|
Overall Study
STARTED
|
32 53
|
34 57
|
|
Overall Study
COMPLETED
|
21 34
|
23 37
|
|
Overall Study
NOT COMPLETED
|
11 19
|
11 20
|
Reasons for withdrawal
| Measure |
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.
Metformin
|
Observation
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.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
10
|
7
|
|
Overall Study
Lost to Follow-up
|
0
|
3
|
|
Overall Study
Ineligible after reviewing baseline imaging
|
1
|
0
|
|
Overall Study
Missing follow-up data
|
0
|
1
|
Baseline Characteristics
Metformin for the Minimization of Geographic Atrophy Progression in Patients With AMD
Baseline characteristics by cohort
| Measure |
Metformin
n=53 eyes
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.
Metformin
|
Observe
n=57 eyes
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.
|
Total
n=110 eyes
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
78.5 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
79.3 years
STANDARD_DEVIATION 7.3 • n=7 Participants
|
78.9 years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
29 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
32 participants
n=5 Participants
|
34 participants
n=7 Participants
|
66 participants
n=5 Participants
|
|
Presence of GA in both eyes
|
27 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
History of cardiovascular diseases
|
19 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
History of respiratory diseases
|
6 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
History of hepatobiliary diseases
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
History of gastrointestinal diseases
|
7 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
History of genitourinary diseases
|
5 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
History of endocrine diseases
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
History of hematological diseases
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
History of musculoskeletal diseases
|
16 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
History of neoplasia
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
History of neurological diseases
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
History of psychological diseases
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
History of immunological diseases
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
History of dermatological diseases
|
2 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
History of allergies
|
9 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
History of ear, nose throat diseases
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
History of other diseases
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Number of eligible eyes
|
53 eyes
n=5 Participants
|
57 eyes
n=7 Participants
|
110 eyes
n=5 Participants
|
|
Best corrected visual acuity
|
58.5 number of letters read on ETDRS
STANDARD_DEVIATION 18.5 • n=5 Participants
|
57.0 number of letters read on ETDRS
STANDARD_DEVIATION 19.4 • n=7 Participants
|
57.7 number of letters read on ETDRS
STANDARD_DEVIATION 18.9 • n=5 Participants
|
|
Low luminance visual acuity
|
42.8 number of letters read on ETDRS
STANDARD_DEVIATION 16.4 • n=5 Participants
|
40.0 number of letters read on ETDRS
STANDARD_DEVIATION 17.9 • n=7 Participants
|
41.3 number of letters read on ETDRS
STANDARD_DEVIATION 17.2 • n=5 Participants
|
|
Geographic atrophy (GA) area
|
6.2 mm^2
STANDARD_DEVIATION 4.4 • n=32 eyes
|
8.7 mm^2
STANDARD_DEVIATION 6.1 • n=16 eyes
|
7.5 mm^2
STANDARD_DEVIATION 5.5 • n=48 eyes
|
|
Multifocal lesion
|
34 eyes
n=32 eyes
|
33 eyes
n=16 eyes
|
67 eyes
n=48 eyes
|
|
Foveal center point involvement
|
45 eyes
n=32 eyes
|
48 eyes
n=16 eyes
|
93 eyes
n=48 eyes
|
|
Fundus autofluorescence (FAF) Pattern, "None" or "Focal"
|
38 eyes
n=32 eyes
|
34 eyes
n=16 eyes
|
72 eyes
n=48 eyes
|
PRIMARY outcome
Timeframe: 0 months, 18 monthsThe 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).
Outcome measures
| Measure |
Metformin
n=34 eyes
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.
Metformin
|
Observation
n=37 eyes
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.
|
|---|---|---|
|
Fundus Autofluorescence Imaging to Measure the Rate of Change in Area of Geographic Atrophy
|
0.41 mm/year
Standard Deviation 0.05
|
0.35 mm/year
Standard Deviation 0.05
|
SECONDARY outcome
Timeframe: 0 months, 18 monthsBCVA is the best possible vision an eye can see with corrective lenses and is measured as then number of letters read on the ETDRS chart. Change = (Month 18 Score - Baseline Score).
Outcome measures
| Measure |
Metformin
n=21 Participants
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.
Metformin
|
Observation
n=23 Participants
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.
|
|---|---|---|
|
Change in Best Corrected Visual Acuity (BCVA)
|
-3.2 letters correctly read
Standard Error 0.9
|
-3.2 letters correctly read
Standard Error 1.3
|
SECONDARY outcome
Timeframe: 0 months, 18 monthsLLVA involves standard BCVA testing in low-light conditions, which is achieved by adding a neutral density filter in front of the eye being tested. LLVA is measured as the number of letters read on the ETDRS chart. This measure has been shown to correlate well with enlargement of GA. Change = (Month 18 Score - Baseline Score).
Outcome measures
| Measure |
Metformin
n=21 Participants
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.
Metformin
|
Observation
n=23 Participants
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.
|
|---|---|---|
|
Change in Low-luminance Visual Acuity (LLVA)
|
-2.1 letters correctly read
Standard Error 2.0
|
-6.3 letters correctly read
Standard Error 1.9
|
SECONDARY outcome
Timeframe: 0 months, 6 months, 12 months, 18 months, 24 monthsSubjects 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. This outcome measures the number of treatment arm patients who experienced adverse ocular events during 1 or more follow-up visits.
Outcome measures
| Measure |
Metformin
n=21 Participants
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.
Metformin
|
Observation
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.
|
|---|---|---|
|
Ocular Safety as Measured by the Presence of Novel Intraocular Inflammation Judged by the Investigator to be Due to the Study Drug Metformin
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: 0 months, 6 months, 12 months, 18 months, 24 monthsThese 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. This outcome measures the number of treatment arm patients who experienced side effects listed on Metformin drug label as "severe" during 1 or more follow-up visits.
Outcome measures
| Measure |
Metformin
n=21 Participants
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.
Metformin
|
Observation
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.
|
|---|---|---|
|
Systemic Safety as Measured by Presence of Side Effects Listed on Metformin Drug Label as "Severe"
|
0 Participants
|
—
|
Adverse Events
Metformin
Serious events: 5 serious events
Other events: 16 other events
Deaths: 0 deaths
Observation
Serious events: 3 serious events
Other events: 4 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Metformin
n=32 participants at risk
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.
Metformin
|
Observation
n=34 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
3.1%
1/32 • Number of events 2 • 24 months
|
2.9%
1/34 • Number of events 2 • 24 months
|
|
Gastrointestinal disorders
Constipation
|
3.1%
1/32 • Number of events 2 • 24 months
|
0.00%
0/34 • 24 months
|
|
Renal and urinary disorders
Acute kidney injury
|
3.1%
1/32 • Number of events 1 • 24 months
|
2.9%
1/34 • Number of events 2 • 24 months
|
|
Vascular disorders
Ascending thoracic aortic aneurysm without rupture
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
Vascular disorders
Deep vein thrombosis
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
Gastrointestinal disorders
Gastroenteritis
|
0.00%
0/32 • 24 months
|
2.9%
1/34 • Number of events 1 • 24 months
|
|
Gastrointestinal disorders
Infectious or inflammatory pancolitis
|
0.00%
0/32 • 24 months
|
2.9%
1/34 • Number of events 1 • 24 months
|
|
Gastrointestinal disorders
Small bowel obstruction
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
Other adverse events
| Measure |
Metformin
n=32 participants at risk
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.
Metformin
|
Observation
n=34 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal discomfort
|
15.6%
5/32 • Number of events 5 • 24 months
|
0.00%
0/34 • 24 months
|
|
Gastrointestinal disorders
Diarrhea
|
15.6%
5/32 • Number of events 5 • 24 months
|
2.9%
1/34 • Number of events 1 • 24 months
|
|
General disorders
Chest pain
|
6.2%
2/32 • Number of events 2 • 24 months
|
0.00%
0/34 • 24 months
|
|
Gastrointestinal disorders
Abdominal pain
|
3.1%
1/32 • Number of events 1 • 24 months
|
2.9%
1/34 • Number of events 1 • 24 months
|
|
General disorders
Fatigue
|
6.2%
2/32 • Number of events 2 • 24 months
|
0.00%
0/34 • 24 months
|
|
General disorders
Fall due to dizziness
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
General disorders
Nausea
|
3.1%
1/32 • Number of events 1 • 24 months
|
2.9%
1/34 • Number of events 2 • 24 months
|
|
Skin and subcutaneous tissue disorders
Rash on back and abdomen
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Leg pain
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
Eye disorders
Dry eyes
|
0.00%
0/32 • 24 months
|
2.9%
1/34 • Number of events 1 • 24 months
|
|
Eye disorders
Development of choroidal neovascularization
|
0.00%
0/32 • 24 months
|
5.9%
2/34 • Number of events 2 • 24 months
|
|
Eye disorders
Development of subretinal hemorrhage
|
3.1%
1/32 • Number of events 1 • 24 months
|
2.9%
1/34 • Number of events 1 • 24 months
|
|
General disorders
Common cold
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
General disorders
Cough
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
General disorders
Subjective complaint of elevated blood pressure
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
Gastrointestinal disorders
Constipation
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
Psychiatric disorders
Irritability and anxiety
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
General disorders
Heartburn
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
Gastrointestinal disorders
Increased lipase
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
|
Hepatobiliary disorders
Hepatic fibrosis of unknown origin
|
3.1%
1/32 • Number of events 1 • 24 months
|
0.00%
0/34 • 24 months
|
Additional Information
Dr. Jay Stewart
University of California, San Francisco
Phone: 628-206-3123
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place