Trial Outcomes & Findings for Effect of Insulin Sensitizer Metformin on AD Biomarkers (NCT NCT01965756)
NCT ID: NCT01965756
Last Updated: 2017-09-21
Results Overview
Alzheimer's Disease Assessment Scale- Cognitive Sub scale (ADAS-COG). Three trials of 10 words each (30 words total)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
16 weeks (total) - measured at baseline, week 8 (crossover), and week 16
Results posted on
2017-09-21
Participant Flow
Participant milestones
| Measure |
Metformin, Then Placebo (Treatment Sequence A, 0 to 16 Weeks)
Participants first received metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached. After 8 weeks, subjects were switched to matching placebo for an additional 8 weeks.
|
Placebo, Then Metformin (Treatment Sequence B, 0 to 16 Weeks)
Participants first received placebo for 8 weeks. After 8 weeks, subjects were switched to metformin, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Insulin Sensitizer Metformin on AD Biomarkers
Baseline characteristics by cohort
| Measure |
Metformin, Then Placebo
n=10 Participants
Participants first received metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached. After 8 weeks, subjects were switched to matching placebo for an additional 8 weeks.
|
Placebo, Then Metformin
n=10 Participants
Participants first received placebo for 8 weeks. After 8 weeks, subjects were switched to metformin, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Age, Continuous
|
69.1 years
STANDARD_DEVIATION 7.40 • n=5 Participants
|
71.1 years
STANDARD_DEVIATION 6.57 • n=7 Participants
|
70.1 years
STANDARD_DEVIATION 6.89 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 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
|
|
Region of Enrollment
United States
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
HbA1c
|
5.5 percentage
STANDARD_DEVIATION 0.221 • n=5 Participants
|
5.37 percentage
STANDARD_DEVIATION 0.236 • n=7 Participants
|
5.44 percentage
STANDARD_DEVIATION 0.232 • n=5 Participants
|
|
Plasma Glucose
|
90.5 mg/dL
STANDARD_DEVIATION 8.77 • n=5 Participants
|
90.9 mg/dL
STANDARD_DEVIATION 14.1 • n=7 Participants
|
90.7 mg/dL
STANDARD_DEVIATION 11.4 • n=5 Participants
|
|
Clinical Dementia Rating - Global (Composite) Score
|
0.5 units on a scale
STANDARD_DEVIATION 0 • n=5 Participants
|
0.8 units on a scale
STANDARD_DEVIATION 0.789 • n=7 Participants
|
0.658 units on a scale
STANDARD_DEVIATION .579 • n=5 Participants
|
PRIMARY outcome
Timeframe: 16 weeks (total) - measured at baseline, week 8 (crossover), and week 16Alzheimer's Disease Assessment Scale- Cognitive Sub scale (ADAS-COG). Three trials of 10 words each (30 words total)
Outcome measures
| Measure |
Metformin, Then Placebo
n=10 Participants
Participants first received metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached. After 8 weeks, subjects were switched to matching placebo for an additional 8 weeks.
|
Placebo, Then Metformin
n=10 Participants
Participants first received placebo for 8 weeks. After 8 weeks, subjects were switched to metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached.
|
|---|---|---|
|
Word List Memory Total - ADAS-cog
Baseline
|
14.35 Words recalled
Standard Deviation 3.96
|
14.7 Words recalled
Standard Deviation 3.33
|
|
Word List Memory Total - ADAS-cog
Week 8
|
15.1 Words recalled
Standard Deviation 4.48
|
14.67 Words recalled
Standard Deviation 3.74
|
|
Word List Memory Total - ADAS-cog
Week 16
|
14.71 Words recalled
Standard Deviation 5.29
|
15.5 Words recalled
Standard Deviation 5.72
|
SECONDARY outcome
Timeframe: 16 weeks- measured at baseline, week 8 (crossover), and week 16Standard Trails-B assessment, in which subject is asked to begin at Number 1 and draw a line to Letter A, then to Number 2, then to Letter B, then so forth until he/she reaches the END, without lifting their pencil. They should draw the line as fast as possible, and are timed (in seconds).
Outcome measures
| Measure |
Metformin, Then Placebo
n=10 Participants
Participants first received metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached. After 8 weeks, subjects were switched to matching placebo for an additional 8 weeks.
|
Placebo, Then Metformin
n=10 Participants
Participants first received placebo for 8 weeks. After 8 weeks, subjects were switched to metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached.
|
|---|---|---|
|
Trails-B
Baseline
|
164.28 Seconds
Standard Deviation 101.22
|
186.7 Seconds
Standard Deviation 83.42
|
|
Trails-B
Week 8
|
164 Seconds
Standard Deviation 95.72
|
170.86 Seconds
Standard Deviation 88.2
|
|
Trails-B
Week 16
|
170.5 Seconds
Standard Deviation 99.99
|
161.8 Seconds
Standard Deviation 91.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and 8 weeksPopulation: CSF was only collected from all participants at baseline and again at week 8 (total of two lumbar punctures). This was pre-specified in the protocol, to ensure adequate tolerability for subjects (total of two lumbar punctures, rather than three). Thus, there is a maximum of 10 data points for each category: 10 for MET--\>PBO, and 10 for PBO--\>MET
Outcome measures
| Measure |
Metformin, Then Placebo
n=10 Participants
Participants first received metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached. After 8 weeks, subjects were switched to matching placebo for an additional 8 weeks.
|
Placebo, Then Metformin
n=10 Participants
Participants first received placebo for 8 weeks. After 8 weeks, subjects were switched to metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached.
|
|---|---|---|
|
Cerebrospinal Fluid Amyloid Beta Concentration
Baseline
|
254.90 pg/mL
Standard Deviation 90.38
|
409.01 pg/mL
Standard Deviation 145.46
|
|
Cerebrospinal Fluid Amyloid Beta Concentration
Week 8
|
266.73 pg/mL
Standard Deviation 26.70
|
424.45 pg/mL
Standard Deviation 117.39
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and 8 weeksPopulation: CSF was only collected from all participants at baseline and again at week 8 (total of two lumbar punctures). This was pre-specified in the protocol, to ensure adequate tolerability for subjects (total of two lumbar punctures, rather than three). Thus, there is a maximum of 10 data points for each category: 10 for MET--\>PBO, and 10 for PBO--\>MET
Outcome measures
| Measure |
Metformin, Then Placebo
n=10 Participants
Participants first received metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached. After 8 weeks, subjects were switched to matching placebo for an additional 8 weeks.
|
Placebo, Then Metformin
n=10 Participants
Participants first received placebo for 8 weeks. After 8 weeks, subjects were switched to metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached.
|
|---|---|---|
|
Cerebrospinal Fluid Total Tau Concentration
Week 8
|
588.53 pg/mL
Standard Deviation 180.02
|
554.47 pg/mL
Standard Deviation 356.44
|
|
Cerebrospinal Fluid Total Tau Concentration
Baseline
|
554.05 pg/mL
Standard Deviation 217.29
|
556.14 pg/mL
Standard Deviation 361.57
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and 8 weeksPopulation: CSF was only collected from all participants at baseline and again at week 8 (total of two lumbar punctures). This was pre-specified in the protocol, to ensure adequate tolerability for subjects (total of two lumbar punctures, rather than three). Thus, there is a maximum of 10 data points for each category: 10 for MET--\>PBO, and 10 for PBO--\>MET
Outcome measures
| Measure |
Metformin, Then Placebo
n=10 Participants
Participants first received metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached. After 8 weeks, subjects were switched to matching placebo for an additional 8 weeks.
|
Placebo, Then Metformin
n=10 Participants
Participants first received placebo for 8 weeks. After 8 weeks, subjects were switched to metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached.
|
|---|---|---|
|
Cerebrospinal Fluid Phosphorylated Tau Concentration
Baseline
|
63.44 pg/mL
Standard Deviation 26.95
|
64.62 pg/mL
Standard Deviation 23.94
|
|
Cerebrospinal Fluid Phosphorylated Tau Concentration
Week 8
|
68.12 pg/mL
Standard Deviation 15.56
|
64.10 pg/mL
Standard Deviation 26.17
|
Adverse Events
Metformin
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Metformin
n=20 participants at risk
This group includes subjects treated with metformin for the first 8 weeks of the study, as well as subjects treated with metformin during the second 8 weeks of the study.
|
Placebo
n=20 participants at risk
This group includes subjects treated with placebo for the first 8 weeks of the study, as well as subjects treated with placebo during the second 8 weeks of the study.
|
|---|---|---|
|
Blood and lymphatic system disorders
Elevated plasma lactate level
|
10.0%
2/20 • Number of events 2 • 2 years, 5 months
|
0.00%
0/20 • 2 years, 5 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place