Trial Outcomes & Findings for Metformin in Amnestic Mild Cognitive Impairment (NCT NCT00620191)
NCT ID: NCT00620191
Last Updated: 2020-10-23
Results Overview
The Selective Reminding Test measures verbal learning and delayed recall through a multiple-trial list-learning paradigm. Patients are presented aurally with a list of 12 words for trial 1 and are asked to recall as many as possible. For trials 2-6, there is a selective presentation of only those words not recalled on the previous trial. Trial 7 is similar to the other trials but is assessed after an 11-minute delay. The score for the selective reminding test is the unweighted average of seven individual study results (min=0 and max=84) Higher scores indicate a better cognitive performance. The total recall score from the first visit was subtracted from that of the last visit to calculate the change in score (total words recalled).
COMPLETED
PHASE2
80 participants
12 months
2020-10-23
Participant Flow
Recruitment was completed in 32 months (2.5 subjects a month) \[38\]; 1426 subjects were screened by telephone and 331 were screened in person.
1426 screened by telephone and 1095 excluded; 331 deemed eligible for in-person screen; 224 of those were excluded; 87 met eligibility criteria, 7 declined randomization, 80 were randomized
Participant milestones
| Measure |
Placebo
placebo identical to metformin.
placebo: placebo identical to metformin 2 tablets twice a day titrated from one table once a day
|
Metformin
metformin 1000 mg twice a day
metformin: metformin 1000 mg twice a day titrated from 500 mg once a day
|
|---|---|---|
|
Overall Study
STARTED
|
40
|
40
|
|
Overall Study
3 Month Follow-up
|
39
|
39
|
|
Overall Study
6 Month Follow-up
|
38
|
36
|
|
Overall Study
9 Month Follow-up
|
37
|
34
|
|
Overall Study
COMPLETED
|
33
|
32
|
|
Overall Study
NOT COMPLETED
|
7
|
8
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Metformin in Amnestic Mild Cognitive Impairment
Baseline characteristics by cohort
| Measure |
Placebo
n=40 Participants
placebo identical to metformin.
placebo: placebo identical to metformin 2 tablets twice a day titrated from one table once a day. Participants remained on the maximum number of tolerated tablets (0,1,2,3,4).
|
Metformin
n=40 Participants
metformin 1000 mg twice a day
metformin: metformin 1000 mg twice a day titrated from 500 mg once a day.Participants remained on the maximum number of tolerated tablets (0,1,2,3,4).
|
Total
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.1 Years
STANDARD_DEVIATION 7.9 • n=5 Participants
|
65.3 Years
STANDARD_DEVIATION 7.0 • n=7 Participants
|
64.5 Years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
13 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
27 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
15 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
13 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
40 participants
n=5 Participants
|
40 participants
n=7 Participants
|
80 participants
n=5 Participants
|
|
APOE Epsilon 4
ApoE Epsilon 4 positive
|
11 participants
n=5 Participants
|
10 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
APOE Epsilon 4
ApoE epsilon 4 negative
|
29 participants
n=5 Participants
|
30 participants
n=7 Participants
|
59 participants
n=5 Participants
|
|
Body Mass Index
|
31.3 kg/m⌃2
STANDARD_DEVIATION 4.7 • n=5 Participants
|
30.9 kg/m⌃2
STANDARD_DEVIATION 4.1 • n=7 Participants
|
31.1 kg/m⌃2
STANDARD_DEVIATION 4.4 • n=5 Participants
|
|
Hemoglobin A1c
|
6.1 percent HbA1c
STANDARD_DEVIATION 0.5 • n=5 Participants
|
6.1 percent HbA1c
STANDARD_DEVIATION 0.8 • n=7 Participants
|
6.1 percent HbA1c
STANDARD_DEVIATION 0.6 • n=5 Participants
|
|
Fasting insulin
|
13.4 IU/dl
STANDARD_DEVIATION 7.6 • n=5 Participants
|
16.3 IU/dl
STANDARD_DEVIATION 9.5 • n=7 Participants
|
14.7 IU/dl
STANDARD_DEVIATION 8.6 • n=5 Participants
|
|
Systolic blood pressure
|
132.1 mmHg
STANDARD_DEVIATION 12.4 • n=5 Participants
|
130.8 mmHg
STANDARD_DEVIATION 10.9 • n=7 Participants
|
131.4 mmHg
STANDARD_DEVIATION 11.6 • n=5 Participants
|
|
Total Cholesterol
|
208.2 mg/dl
STANDARD_DEVIATION 46.7 • n=5 Participants
|
204.2 mg/dl
STANDARD_DEVIATION 43.6 • n=7 Participants
|
206.2 mg/dl
STANDARD_DEVIATION 44.9 • n=5 Participants
|
|
High Density lipoprotein
|
58.3 mg/dl
STANDARD_DEVIATION 17.7 • n=5 Participants
|
51.5 mg/dl
STANDARD_DEVIATION 14.1 • n=7 Participants
|
54.8 mg/dl
STANDARD_DEVIATION 16.2 • n=5 Participants
|
|
Score of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)
|
14.6 score
STANDARD_DEVIATION 6.1 • n=5 Participants
|
12.0 score
STANDARD_DEVIATION 4.0 • n=7 Participants
|
13.3 score
STANDARD_DEVIATION 5.3 • n=5 Participants
|
|
Selective Reminding Test Total Recall score
|
36.1 score
STANDARD_DEVIATION 9.5 • n=5 Participants
|
34.2 score
STANDARD_DEVIATION 7.9 • n=7 Participants
|
35.2 score
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Education in Years
|
13.1 Years
STANDARD_DEVIATION 4.5 • n=5 Participants
|
13.8 Years
STANDARD_DEVIATION 3.4 • n=7 Participants
|
13.4 Years
STANDARD_DEVIATION 4.0 • n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsThe Selective Reminding Test measures verbal learning and delayed recall through a multiple-trial list-learning paradigm. Patients are presented aurally with a list of 12 words for trial 1 and are asked to recall as many as possible. For trials 2-6, there is a selective presentation of only those words not recalled on the previous trial. Trial 7 is similar to the other trials but is assessed after an 11-minute delay. The score for the selective reminding test is the unweighted average of seven individual study results (min=0 and max=84) Higher scores indicate a better cognitive performance. The total recall score from the first visit was subtracted from that of the last visit to calculate the change in score (total words recalled).
Outcome measures
| Measure |
Placebo
n=40 Participants
Placebo identical to metformin.
placebo: placebo identical to metformin 2 tablets twice a day titrated from one tablet once a day. Participants remained on the highest tolerated dose (0,1,2,3,4 tablets).
|
Metformin
n=40 Participants
Metformin 1000 mg twice a day
metformin: metformin 1000 mg twice a day titrated from 500 mg once a day. Participants remained on the highest tolerated dose (0,1,2,3,4 tablets of 500 mg each).
|
|---|---|---|
|
Change in Total Recall Score in the Selective Reminding Test
|
5.7 score on a scale
Standard Deviation 8.7
|
9.4 score on a scale
Standard Deviation 8.5
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: Analyses used an intent to treat approach with last observation carried forward
The ADAS-cog is an aggregate for several cognitive tests intended to provide a global cognitive score and consists of 11 tasks. The tasks (and corresponding score range)) are Word Recall (0-10), Naming (0-4), Commands (0-5), Constructional Praxis (0-5) Ideational Praxis (0-5), Orientation (0-8), Word Recognition (0-12), Language (0-5), Word Finding Difficulty (0-5), and Remembering Test Instructions (1-5). The range of aggregate scores (sum of scores) is 1 to 69, with higher scores meaning worse cognitive performance. The change was calculated subtracting the baseline score from the final visit score.
Outcome measures
| Measure |
Placebo
n=40 Participants
Placebo identical to metformin.
placebo: placebo identical to metformin 2 tablets twice a day titrated from one tablet once a day. Participants remained on the highest tolerated dose (0,1,2,3,4 tablets).
|
Metformin
n=40 Participants
Metformin 1000 mg twice a day
metformin: metformin 1000 mg twice a day titrated from 500 mg once a day. Participants remained on the highest tolerated dose (0,1,2,3,4 tablets of 500 mg each).
|
|---|---|---|
|
Change in Score of the Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog)
|
-1.98 score
Standard Deviation 5.5
|
0.0 score
Standard Deviation 3.3
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Out of 40 persons recruited in the imaging sub study, 33 underwent a 12 month scan (18 in the placebo group, 15 in the metformin group).
Change in relative glucose uptake (rCMRgl) in the posterior cingulate-precuneus measured with subscale (ADAS-Cog) from brain \[18\]F-labeled 2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET). The unit for rCMRgl is %. The results presented are absolute differences in rCMRgl, presented in % units; the change was calculated subtracting the baseline rCMRgl from the follow-up rCMRgl
Outcome measures
| Measure |
Placebo
n=18 Participants
Placebo identical to metformin.
placebo: placebo identical to metformin 2 tablets twice a day titrated from one tablet once a day. Participants remained on the highest tolerated dose (0,1,2,3,4 tablets).
|
Metformin
n=15 Participants
Metformin 1000 mg twice a day
metformin: metformin 1000 mg twice a day titrated from 500 mg once a day. Participants remained on the highest tolerated dose (0,1,2,3,4 tablets of 500 mg each).
|
|---|---|---|
|
Change in Relative Glucose Uptake (rCMRg) in the Posterior Cingulate-precuneus.
|
0.0 percentage of rCMRgl
Standard Deviation 6.0
|
2.0 percentage of rCMRgl
Standard Deviation 6.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 monthsChange in plasma Amyloid beta-42 from baseline to 12 months
Outcome measures
| Measure |
Placebo
n=40 Participants
Placebo identical to metformin.
placebo: placebo identical to metformin 2 tablets twice a day titrated from one tablet once a day. Participants remained on the highest tolerated dose (0,1,2,3,4 tablets).
|
Metformin
n=40 Participants
Metformin 1000 mg twice a day
metformin: metformin 1000 mg twice a day titrated from 500 mg once a day. Participants remained on the highest tolerated dose (0,1,2,3,4 tablets of 500 mg each).
|
|---|---|---|
|
Change in Plasma Amyloid Beta-42
|
-4.40 pg/ml
Standard Deviation 23.51
|
0.69 pg/ml
Standard Deviation 18.5
|
Adverse Events
Placebo
Metformin
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=40 participants at risk
Matching placebo
placebo: matching identical to metformin 2 tablets twice a day titrated from one table once a day
|
Metformin
n=40 participants at risk
metformin 1000 mg twice a day
metformin: metformin 1000 mg twice a day titrated from 500 mg once a day
|
|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal symptoms
|
0.00%
0/40 • 12 months
The adverse event data were collected during the 12 months of the duration of the trial
|
7.5%
3/40 • Number of events 3 • 12 months
The adverse event data were collected during the 12 months of the duration of the trial
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place