Trial Outcomes & Findings for A Double-Blind, Placebo-Controlled Trial of Anti-Aging, Pro-Autophagy Effects of Metformin in Adults With Prediabetes (NCT NCT03309007)
NCT ID: NCT03309007
Last Updated: 2023-12-11
Results Overview
During the process of autophagy, autophagosomes engulf cytoplasmic components and concomitantly, the cytosolic form of LC3 (LC3-I) is conjugated to phosphatidyl ethanolamine, resulting in the autophagosomal membrane-bound form (LC3-II). LC3-II is a widely used marker to monitor autophagosome formation by quantitation of the number of LC3-labeled puncta (autophagosomes, or "dots") per cell detected by fluorescence microscopy. An increase in LC3 puncta formation denotes an increase in autophagic activity.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
25 participants
Primary outcome timeframe
Data will be collected at 0 and 12 weeks and analyzed within 8 weeks of sample collection.
Results posted on
2023-12-11
Participant Flow
Participant milestones
| Measure |
Metformin
Metformin started at 500 mg po twice daily (BID), and then titrated up to 1000 mg po q morning (AM) and 500 po q evening (PM) over the course of 1 month, as tolerated.
Metformin: Total daily dose titrated up to 1500 mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks.
|
Placebo Oral Tablet
Near-identical CaCO3 as a Placebo Oral Tablet will be started at 648 mg po BID, and then titrated up to 1296 mg po q AM and 648 mg po q PM over the course of 1 month, as tolerated.
Placebo Oral Tablet: Total daily dose titrated up to 1944 mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
12
|
|
Overall Study
COMPLETED
|
13
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Total 25 enrolled
Baseline characteristics by cohort
| Measure |
Metformin
n=13 Participants
Metformin 500 mg po BID titrated to 1000 q AM and 500 q PM over one month, as tolerated.
|
Placebo Oral Tablet
n=12 Participants
Placebo (CaCO3) 648 mg po BID titrated to 1296 qAM and 648 q PM over one month, as tolerated.
|
Total
n=25 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
|
10 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Age, Continuous
|
59.3 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
62.3 years
STANDARD_DEVIATION 7.4 • n=7 Participants
|
60.8 years
STANDARD_DEVIATION 9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants • Total 25 enrolled
|
0 Participants
n=7 Participants • Total 25 enrolled
|
1 Participants
n=5 Participants • Total 25 enrolled
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants • Total 25 enrolled
|
0 Participants
n=7 Participants • Total 25 enrolled
|
0 Participants
n=5 Participants • Total 25 enrolled
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants • Total 25 enrolled
|
0 Participants
n=7 Participants • Total 25 enrolled
|
0 Participants
n=5 Participants • Total 25 enrolled
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants • Total 25 enrolled
|
0 Participants
n=7 Participants • Total 25 enrolled
|
1 Participants
n=5 Participants • Total 25 enrolled
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants • Total 25 enrolled
|
12 Participants
n=7 Participants • Total 25 enrolled
|
23 Participants
n=5 Participants • Total 25 enrolled
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants • Total 25 enrolled
|
0 Participants
n=7 Participants • Total 25 enrolled
|
0 Participants
n=5 Participants • Total 25 enrolled
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants • Total 25 enrolled
|
0 Participants
n=7 Participants • Total 25 enrolled
|
0 Participants
n=5 Participants • Total 25 enrolled
|
|
Region of Enrollment
United States
|
13 participants
n=5 Participants
|
12 participants
n=7 Participants
|
25 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Data will be collected at 0 and 12 weeks and analyzed within 8 weeks of sample collection.During the process of autophagy, autophagosomes engulf cytoplasmic components and concomitantly, the cytosolic form of LC3 (LC3-I) is conjugated to phosphatidyl ethanolamine, resulting in the autophagosomal membrane-bound form (LC3-II). LC3-II is a widely used marker to monitor autophagosome formation by quantitation of the number of LC3-labeled puncta (autophagosomes, or "dots") per cell detected by fluorescence microscopy. An increase in LC3 puncta formation denotes an increase in autophagic activity.
Outcome measures
| Measure |
Metformin
n=13 Participants
Metformin started at 500 mg po twice daily (BID), and then titrated up to 1000 mg po q morning (AM) and 500 po q evening (PM) over the course of 1 month, as tolerated.
Metformin: Total daily dose titrated up to 1500 mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks.
|
Placebo Oral Tablet
n=12 Participants
Near-identical CaCO3 as a Placebo Oral Tablet will be started at 648 mg po BID, and then titrated up to 1296 mg po q AM and 648 mg po q PM over the course of 1 month, as tolerated.
Placebo Oral Tablet: Total daily dose titrated up to 1944 mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks.
|
|---|---|---|
|
Change in Leucocyte LC3 Score
|
0.1 Fold Change (Arbitrary Units)
Standard Deviation 3.4
|
-1.8 Fold Change (Arbitrary Units)
Standard Deviation 3.0
|
Adverse Events
Metformin
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo Oral Tablet
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=13 participants at risk
Metformin started at 500 mg po twice daily (BID), and then titrated up to 1000 mg po q morning (AM) and 500 po q evening (PM) over the course of 1 month, as tolerated.
Metformin: Total daily dose titrated up to 1500 mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks.
|
Placebo Oral Tablet
n=12 participants at risk
Near-identical CaCO3 as a Placebo Oral Tablet will be started at 648 mg po BID, and then titrated up to 1296 mg po q AM and 648 mg po q PM over the course of 1 month, as tolerated.
Placebo Oral Tablet: Total daily dose titrated up to 1944 mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
7.7%
1/13 • Number of events 1 • 12 weeks
|
0.00%
0/12 • 12 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place