Trial Outcomes & Findings for Pioglitazone Or Exercise to Treat Mild Cognitive Impairment (MCI) (NCT NCT00736996)
NCT ID: NCT00736996
Last Updated: 2016-01-15
Results Overview
Participants were administered a neuropsychological testing battery consisting of assessments in four cognitive domains: memory (Visual Reproduction II, Logical Memory II, Rey Auditory Verbal Learning Test), language (Boston Naming Test , Category Fluency), visuospatial (Block Design, Picture Completion), and executive function (Trail Making Test B, Digit Symbol Test). Raw test scores for these primary cognitive domain measures were transformed into age-adjusted scaled scores with a mean of 10 and a standard deviation (SD) of 3, with higher numbers indicating better cognitive performance, using the Mayo's Older American Normative Studies data. Cognitive domain scores were calculated as the arithmetic mean of the normatively derived scaled scores for all of the tests in that domain.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
78 participants
Primary outcome timeframe
Baseline to 6 months
Results posted on
2016-01-15
Participant Flow
Participant milestones
| Measure |
Pioglitazone
Pioglitazone: 45mg oral tablet daily for 6 months
|
Endurance Exercise Training
Endurance Exercise Training: Supervised, thrice-weekly, 45-75 minute sessions of treadmill walking, initially moderate intensity (50-60% of maximum heart rate), with progressive increases in intensity to the best of the subject's ability, up to 85% of maximal heart rate.
|
Placebo
Placebo: Matching oral tablet daily for 6 months
|
|---|---|---|---|
|
Overall Study
STARTED
|
25
|
26
|
27
|
|
Overall Study
COMPLETED
|
24
|
17
|
25
|
|
Overall Study
NOT COMPLETED
|
1
|
9
|
2
|
Reasons for withdrawal
| Measure |
Pioglitazone
Pioglitazone: 45mg oral tablet daily for 6 months
|
Endurance Exercise Training
Endurance Exercise Training: Supervised, thrice-weekly, 45-75 minute sessions of treadmill walking, initially moderate intensity (50-60% of maximum heart rate), with progressive increases in intensity to the best of the subject's ability, up to 85% of maximal heart rate.
|
Placebo
Placebo: Matching oral tablet daily for 6 months
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
9
|
2
|
Baseline Characteristics
Pioglitazone Or Exercise to Treat Mild Cognitive Impairment (MCI)
Baseline characteristics by cohort
| Measure |
Pioglitazone
n=24 Participants
Pioglitazone: 45mg oral tablet daily for 6 months
|
Endurance Exercise Training
n=17 Participants
Endurance Exercise Training: Supervised, thrice-weekly, 45-75 minute sessions of treadmill walking, initially moderate intensity (50-60% of maximum heart rate), with progressive increases in intensity to the best of the subject's ability, up to 85% of maximal heart rate.
|
Placebo
n=25 Participants
Placebo: Matching oral tablet daily for 6 months
|
Total
n=66 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
17 participants
n=7 Participants
|
25 participants
n=5 Participants
|
66 participants
n=4 Participants
|
|
Age, Continuous
|
65 years
STANDARD_DEVIATION 6 • n=5 Participants
|
64 years
STANDARD_DEVIATION 7 • n=7 Participants
|
68 years
STANDARD_DEVIATION 7 • n=5 Participants
|
65 years
STANDARD_DEVIATION 7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
35 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
20 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
61 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 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
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to 6 monthsParticipants were administered a neuropsychological testing battery consisting of assessments in four cognitive domains: memory (Visual Reproduction II, Logical Memory II, Rey Auditory Verbal Learning Test), language (Boston Naming Test , Category Fluency), visuospatial (Block Design, Picture Completion), and executive function (Trail Making Test B, Digit Symbol Test). Raw test scores for these primary cognitive domain measures were transformed into age-adjusted scaled scores with a mean of 10 and a standard deviation (SD) of 3, with higher numbers indicating better cognitive performance, using the Mayo's Older American Normative Studies data. Cognitive domain scores were calculated as the arithmetic mean of the normatively derived scaled scores for all of the tests in that domain.
Outcome measures
| Measure |
Pioglitazone
n=24 Participants
Pioglitazone: 45mg oral tablet daily for 6 months
|
Endurance Exercise Training
n=17 Participants
Endurance Exercise Training: Supervised, thrice-weekly, 45-75 minute sessions of treadmill walking, initially moderate intensity (50-60% of maximum heart rate), with progressive increases in intensity to the best of the subject's ability, up to 85% of maximal heart rate.
|
Placebo
n=25 Participants
Placebo: Matching oral tablet daily for 6 months
|
|---|---|---|---|
|
Change in Cognitive Performance
Memory domain
|
0.8 units on a scale
Interval -1.4 to 2.9
|
0.7 units on a scale
Interval -1.5 to 2.8
|
1.2 units on a scale
Interval -1.0 to 3.4
|
|
Change in Cognitive Performance
Language domain
|
0.4 units on a scale
Interval -1.8 to 2.6
|
0.6 units on a scale
Interval -1.6 to 2.8
|
0.4 units on a scale
Interval -1.9 to 2.6
|
|
Change in Cognitive Performance
Visuospatial domain
|
0.3 units on a scale
Interval -1.7 to 2.3
|
1.1 units on a scale
Interval -0.9 to 3.1
|
0.8 units on a scale
Interval -1.2 to 2.8
|
|
Change in Cognitive Performance
Executive function domain
|
1.0 units on a scale
Interval -0.9 to 3.0
|
0.7 units on a scale
Interval -1.2 to 2.6
|
0.9 units on a scale
Interval -1.1 to 2.9
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsChange in whole body glucose disposal rate (mg/kg/min) calculated during a single-stage (40 mU/m2/min), 3-hour hyperinsulinemic, euglycemic clamp
Outcome measures
| Measure |
Pioglitazone
n=24 Participants
Pioglitazone: 45mg oral tablet daily for 6 months
|
Endurance Exercise Training
n=17 Participants
Endurance Exercise Training: Supervised, thrice-weekly, 45-75 minute sessions of treadmill walking, initially moderate intensity (50-60% of maximum heart rate), with progressive increases in intensity to the best of the subject's ability, up to 85% of maximal heart rate.
|
Placebo
n=25 Participants
Placebo: Matching oral tablet daily for 6 months
|
|---|---|---|---|
|
Change in Insulin Resistance
|
1.7 mg/kg/min
Interval 0.9 to 2.4
|
0.7 mg/kg/min
Interval -0.1 to 1.6
|
0.1 mg/kg/min
Interval -0.6 to 0.8
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsPeak oxygen consumption (VO2 peak, ml/kg/min) was determined by open circuit spirometry during a standard treadmill stress test (modified Balke protocol).
Outcome measures
| Measure |
Pioglitazone
n=24 Participants
Pioglitazone: 45mg oral tablet daily for 6 months
|
Endurance Exercise Training
n=17 Participants
Endurance Exercise Training: Supervised, thrice-weekly, 45-75 minute sessions of treadmill walking, initially moderate intensity (50-60% of maximum heart rate), with progressive increases in intensity to the best of the subject's ability, up to 85% of maximal heart rate.
|
Placebo
n=25 Participants
Placebo: Matching oral tablet daily for 6 months
|
|---|---|---|---|
|
Change in Peak Oxygen Uptake (VO2 Peak)
|
0.9 ml/kg/min
Interval -4.6 to 6.4
|
3.2 ml/kg/min
Interval -2.3 to 8.7
|
1.3 ml/kg/min
Interval -4.1 to 6.7
|
Adverse Events
Pioglitazone
Serious events: 3 serious events
Other events: 18 other events
Deaths: 0 deaths
Endurance Exercise Training
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
Placebo
Serious events: 3 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pioglitazone
n=25 participants at risk
Pioglitazone: 45mg oral tablet daily for 6 months
|
Endurance Exercise Training
n=26 participants at risk
Endurance Exercise Training: Supervised, thrice-weekly, 45-75 minute sessions of treadmill walking, initially moderate intensity (50-60% of maximum heart rate), with progressive increases in intensity to the best of the subject's ability, up to 85% of maximal heart rate.
|
Placebo
n=27 participants at risk
Placebo: Matching oral tablet daily for 6 months
|
|---|---|---|---|
|
Cardiac disorders
Paroxysmal supraventricular tachycardia
|
4.0%
1/25 • Number of events 1 • 6 months
|
0.00%
0/26 • 6 months
|
0.00%
0/27 • 6 months
|
|
Cardiac disorders
Syncope
|
0.00%
0/25 • 6 months
|
0.00%
0/26 • 6 months
|
3.7%
1/27 • Number of events 1 • 6 months
|
|
Cardiac disorders
Atrial fibrillation
|
4.0%
1/25 • Number of events 1 • 6 months
|
0.00%
0/26 • 6 months
|
0.00%
0/27 • 6 months
|
|
Injury, poisoning and procedural complications
Hypoglycemia
|
0.00%
0/25 • 6 months
|
0.00%
0/26 • 6 months
|
3.7%
1/27 • Number of events 1 • 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.00%
0/25 • 6 months
|
3.8%
1/26 • Number of events 1 • 6 months
|
0.00%
0/27 • 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Kidney mass
|
0.00%
0/25 • 6 months
|
0.00%
0/26 • 6 months
|
3.7%
1/27 • Number of events 1 • 6 months
|
|
General disorders
Dehydration
|
4.0%
1/25 • Number of events 1 • 6 months
|
0.00%
0/26 • 6 months
|
0.00%
0/27 • 6 months
|
Other adverse events
| Measure |
Pioglitazone
n=25 participants at risk
Pioglitazone: 45mg oral tablet daily for 6 months
|
Endurance Exercise Training
n=26 participants at risk
Endurance Exercise Training: Supervised, thrice-weekly, 45-75 minute sessions of treadmill walking, initially moderate intensity (50-60% of maximum heart rate), with progressive increases in intensity to the best of the subject's ability, up to 85% of maximal heart rate.
|
Placebo
n=27 participants at risk
Placebo: Matching oral tablet daily for 6 months
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
12.0%
3/25 • Number of events 4 • 6 months
|
42.3%
11/26 • Number of events 11 • 6 months
|
22.2%
6/27 • Number of events 6 • 6 months
|
|
Cardiac disorders
Cardiovascular
|
16.0%
4/25 • Number of events 5 • 6 months
|
7.7%
2/26 • Number of events 2 • 6 months
|
14.8%
4/27 • Number of events 5 • 6 months
|
|
Skin and subcutaneous tissue disorders
Dermatologic
|
12.0%
3/25 • Number of events 4 • 6 months
|
3.8%
1/26 • Number of events 1 • 6 months
|
18.5%
5/27 • Number of events 5 • 6 months
|
|
Gastrointestinal disorders
Gastrointestinal
|
20.0%
5/25 • Number of events 6 • 6 months
|
23.1%
6/26 • Number of events 7 • 6 months
|
14.8%
4/27 • Number of events 4 • 6 months
|
|
General disorders
General
|
40.0%
10/25 • Number of events 10 • 6 months
|
19.2%
5/26 • Number of events 8 • 6 months
|
22.2%
6/27 • Number of events 6 • 6 months
|
|
Ear and labyrinth disorders
ENT
|
12.0%
3/25 • Number of events 4 • 6 months
|
3.8%
1/26 • Number of events 1 • 6 months
|
3.7%
1/27 • Number of events 1 • 6 months
|
|
Endocrine disorders
Endocrine
|
0.00%
0/25 • 6 months
|
11.5%
3/26 • Number of events 5 • 6 months
|
3.7%
1/27 • Number of events 2 • 6 months
|
|
Blood and lymphatic system disorders
Hematologic
|
8.0%
2/25 • Number of events 2 • 6 months
|
0.00%
0/26 • 6 months
|
3.7%
1/27 • Number of events 1 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary
|
8.0%
2/25 • Number of events 2 • 6 months
|
3.8%
1/26 • Number of events 1 • 6 months
|
11.1%
3/27 • Number of events 3 • 6 months
|
|
Renal and urinary disorders
Genitourinary
|
4.0%
1/25 • Number of events 1 • 6 months
|
7.7%
2/26 • Number of events 2 • 6 months
|
11.1%
3/27 • Number of events 4 • 6 months
|
|
Nervous system disorders
Neurologic
|
4.0%
1/25 • Number of events 1 • 6 months
|
3.8%
1/26 • Number of events 1 • 6 months
|
11.1%
3/27 • Number of events 3 • 6 months
|
|
Psychiatric disorders
Behavioral
|
0.00%
0/25 • 6 months
|
3.8%
1/26 • Number of events 1 • 6 months
|
3.7%
1/27 • Number of events 1 • 6 months
|
|
Infections and infestations
Infectious Disease
|
8.0%
2/25 • Number of events 2 • 6 months
|
0.00%
0/26 • 6 months
|
0.00%
0/27 • 6 months
|
|
Eye disorders
Opthalmologic
|
8.0%
2/25 • Number of events 2 • 6 months
|
0.00%
0/26 • 6 months
|
0.00%
0/27 • 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place