Trial Outcomes & Findings for The INCREASE Study - Delaying the Onset of Alzheimer's Symptomatic Expression (NCT NCT02849639)
NCT ID: NCT02849639
Last Updated: 2023-07-19
Results Overview
Change from baseline to end of study. The Medication Appropriateness Index (MAI) rates medications as "appropriate", "marginally appropriate", or "inappropriate" based on ten criteria. All medications reported by study participants were evaluated by the study team and assigned a medication-specific MAI. As an outcome measure, the total MAI was obtained by adding the medication specific MAIs for all medications reported by the participant. Minimum score for one medication is 0 (appropriate) and the maximum is 18 (inappropriate for all criteria). Total MAI depends on the number of medications taken by participant. A decrease in MAI from baseline to end of study indicates improvement in medication appropriateness.
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
90 participants
Primary outcome timeframe
change from baseline to end of study, an average of 1 year
Results posted on
2023-07-19
Participant Flow
Participant milestones
| Measure |
Placebo
Participants enrolled into this arm will only receive educational materials, but will not receive specific recommendations to make changes to the medications they are taking.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Placebo: Participants will receive educational materials, but will not receive MTM.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
Medication Therapy Management (MTM)
Participants enrolled into this arm will receive educational materials and will have their medications assessed; recommendations for changes in the medications taken will be made when appropriate.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Medication Therapy Management (MTM): Participants will receive MTM in addition to the educational materials.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
|---|---|---|
|
Overall Study
STARTED
|
44
|
46
|
|
Overall Study
COMPLETED
|
41
|
44
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The INCREASE Study - Delaying the Onset of Alzheimer's Symptomatic Expression
Baseline characteristics by cohort
| Measure |
Placebo
n=44 Participants
Participants enrolled into this arm will only receive educational materials, but will not receive specific recommendations to make changes to the medications they are taking.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Placebo: Participants will receive educational materials, but will not receive MTM.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
Medication Therapy Management (MTM)
n=46 Participants
Participants enrolled into this arm will receive educational materials and will have their medications assessed; recommendations for changes in the medications taken will be made when appropriate.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Medication Therapy Management (MTM): Participants will receive MTM in addition to the educational materials.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
Total
n=90 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
74.1 years
STANDARD_DEVIATION 6.6 • n=93 Participants
|
73.4 years
STANDARD_DEVIATION 5.6 • n=4 Participants
|
73.9 years
STANDARD_DEVIATION 6.0 • n=27 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=93 Participants
|
34 Participants
n=4 Participants
|
57 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
33 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
44 Participants
n=93 Participants
|
46 Participants
n=4 Participants
|
90 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
40 Participants
n=93 Participants
|
40 Participants
n=4 Participants
|
80 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Standardized Uptake Value ratio
SUVr<1.2
|
13 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
27 Participants
n=27 Participants
|
|
Standardized Uptake Value ratio
1.2<=SUVr<1.4
|
17 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
34 Participants
n=27 Participants
|
|
Standardized Uptake Value ratio
SUVr>=1.4
|
14 Participants
n=93 Participants
|
15 Participants
n=4 Participants
|
29 Participants
n=27 Participants
|
|
Years of education
|
16.4 years
STANDARD_DEVIATION 2.6 • n=93 Participants
|
16.5 years
STANDARD_DEVIATION 3.0 • n=4 Participants
|
16.5 years
STANDARD_DEVIATION 2.8 • n=27 Participants
|
|
Total number of medications
|
12.9 medications
STANDARD_DEVIATION 4.8 • n=93 Participants
|
12.7 medications
STANDARD_DEVIATION 5.0 • n=4 Participants
|
12.8 medications
STANDARD_DEVIATION 4.8 • n=27 Participants
|
|
Number of medications on 2015 Beers list
|
2.2 medications
STANDARD_DEVIATION 1.2 • n=93 Participants
|
2.5 medications
STANDARD_DEVIATION 1.2 • n=4 Participants
|
2.4 medications
STANDARD_DEVIATION 1.2 • n=27 Participants
|
|
Medication appropriateness index
|
10.6 units on a scale
STANDARD_DEVIATION 7.4 • n=93 Participants
|
13.5 units on a scale
STANDARD_DEVIATION 9.4 • n=4 Participants
|
12.1 units on a scale
STANDARD_DEVIATION 8.5 • n=27 Participants
|
PRIMARY outcome
Timeframe: change from baseline to end of study, an average of 1 yearChange from baseline to end of study. The Medication Appropriateness Index (MAI) rates medications as "appropriate", "marginally appropriate", or "inappropriate" based on ten criteria. All medications reported by study participants were evaluated by the study team and assigned a medication-specific MAI. As an outcome measure, the total MAI was obtained by adding the medication specific MAIs for all medications reported by the participant. Minimum score for one medication is 0 (appropriate) and the maximum is 18 (inappropriate for all criteria). Total MAI depends on the number of medications taken by participant. A decrease in MAI from baseline to end of study indicates improvement in medication appropriateness.
Outcome measures
| Measure |
Placebo
n=41 Participants
Participants enrolled into this arm will only receive educational materials, but will not receive specific recommendations to make changes to the medications they are taking.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Placebo: Participants will receive educational materials, but will not receive MTM.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
Medication Therapy Management (MTM)
n=44 Participants
Participants enrolled into this arm will receive educational materials and will have their medications assessed; recommendations for changes in the medications taken will be made when appropriate.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Medication Therapy Management (MTM): Participants will receive MTM in addition to the educational materials.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
|---|---|---|
|
Medication Appropriateness Index
|
11.2 units on a scale
Standard Error 0.6
|
9.4 units on a scale
Standard Error 0.6
|
PRIMARY outcome
Timeframe: baseline to end of study, an average of 1 yearEnd of study for Trail Making Test B with the scopolamine patch. The mean and standard used to compute the TMTB z-scores were taken from a sample of cognitively intact older adult research volunteers (Weintraub et al. 2009; mean = 90.3, SD = 50) (22). Z-scores were then multiplied by -1 to facilitate interpretation, since higher TMTB scores are worse. For the z-score, we converted time in seconds to units of standard deviations from a mean of 0, where 0 represents the mean performance of cognitively intact (normal) older adult research volunteers enrolled in longitudinal studies at Alzheimer's Disease Research Centers in the United States. Scores that are at least 1.5 standard deviations below the mean are indicative of potential cognitive impairment.
Outcome measures
| Measure |
Placebo
n=40 Participants
Participants enrolled into this arm will only receive educational materials, but will not receive specific recommendations to make changes to the medications they are taking.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Placebo: Participants will receive educational materials, but will not receive MTM.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
Medication Therapy Management (MTM)
n=42 Participants
Participants enrolled into this arm will receive educational materials and will have their medications assessed; recommendations for changes in the medications taken will be made when appropriate.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Medication Therapy Management (MTM): Participants will receive MTM in addition to the educational materials.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
|---|---|---|
|
Trail Making Test B With the Scopolamine Patch
|
-0.1 z-scores
Standard Error 0.14
|
0.03 z-scores
Standard Error 0.14
|
SECONDARY outcome
Timeframe: change from baseline to end of study, an average of 1 yearPopulation: MoCA (Z score, NACC UDS norms), challenged condition
Change from baseline to end of study for Montreal Cognitive Assessment. Z score is based on the NACC cognitively normal population (https://files.alz.washington.edu/documentation/weintraub-2018-v3.pdf), Z score = 0 corresponds mean MoCA score for cognitively normal older adults; higher Z scores are better; typical neuropsych interpretation of z scores is that -1.5 indicates impaired performance on that test.
Outcome measures
| Measure |
Placebo
n=41 Participants
Participants enrolled into this arm will only receive educational materials, but will not receive specific recommendations to make changes to the medications they are taking.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Placebo: Participants will receive educational materials, but will not receive MTM.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
Medication Therapy Management (MTM)
n=44 Participants
Participants enrolled into this arm will receive educational materials and will have their medications assessed; recommendations for changes in the medications taken will be made when appropriate.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Medication Therapy Management (MTM): Participants will receive MTM in addition to the educational materials.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
|---|---|---|
|
Cognitive Reserve: Montreal Cognitive Assessment
|
-0.15 z-score
Standard Error 0.12
|
-0.31 z-score
Standard Error 0.13
|
SECONDARY outcome
Timeframe: change from baseline to end of study, an average of 1 yearPopulation: CVLT Long Delay (Z score), challenged condition
Change from baseline to end of study for California Verbal Learning test. Z scores (higher scores are better; Z score = 0 corresponds mean CVLT score for cognitively normal older adults; typical neuropsych interpretation of z scores is that -1.5 indicates impaired performance on that test) are adjusted for age and sex and are based on the normative population used to develop norms for CVLT-II; "individuals sampled to create the normative data were tested cross-sectionally, demographically matched to the most recent U.S. Censuses, and screened for self-reported neurological, psychiatric, or debilitating medical illnesses." Delis, D. C., Kramer, J. H., Kaplan, E., \& Ober, B. A. (1987-2000). California Verbal Learning Test--Second Edition (CVLT -II) \[Database record\]. APA PsycTests. https://doi.org/10.1037/t15072-000
Outcome measures
| Measure |
Placebo
n=41 Participants
Participants enrolled into this arm will only receive educational materials, but will not receive specific recommendations to make changes to the medications they are taking.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Placebo: Participants will receive educational materials, but will not receive MTM.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
Medication Therapy Management (MTM)
n=44 Participants
Participants enrolled into this arm will receive educational materials and will have their medications assessed; recommendations for changes in the medications taken will be made when appropriate.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Medication Therapy Management (MTM): Participants will receive MTM in addition to the educational materials.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
|---|---|---|
|
Cognitive Reserve: California Verbal Learning Test
|
-0.10 z-score
Standard Error 0.15
|
-0.083 z-score
Standard Error 0.14
|
SECONDARY outcome
Timeframe: change from baseline to end of study, an average of 1 yearPopulation: SF-36 Mental Component Score (T score), challenged condition
Change from baseline to end of study for Short Form Health Survey (SF-36). T scores have a mean of 50 and SD of 10; higher scores are better; mean = 50 represents expected mean in general US adult population, with no available clinically relevant thresholds .
Outcome measures
| Measure |
Placebo
n=41 Participants
Participants enrolled into this arm will only receive educational materials, but will not receive specific recommendations to make changes to the medications they are taking.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Placebo: Participants will receive educational materials, but will not receive MTM.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
Medication Therapy Management (MTM)
n=44 Participants
Participants enrolled into this arm will receive educational materials and will have their medications assessed; recommendations for changes in the medications taken will be made when appropriate.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Medication Therapy Management (MTM): Participants will receive MTM in addition to the educational materials.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
|---|---|---|
|
Perceived Health Status
|
41.4 t-score
Standard Error 1.2
|
41.2 t-score
Standard Error 1.3
|
Adverse Events
Placebo
Serious events: 9 serious events
Other events: 42 other events
Deaths: 2 deaths
Medication Therapy Management (MTM)
Serious events: 7 serious events
Other events: 41 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=44 participants at risk
Participants enrolled into this arm will only receive educational materials, but will not receive specific recommendations to make changes to the medications they are taking.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Placebo: Participants will receive educational materials, but will not receive MTM.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
Medication Therapy Management (MTM)
n=46 participants at risk
Participants enrolled into this arm will receive educational materials and will have their medications assessed; recommendations for changes in the medications taken will be made when appropriate.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Medication Therapy Management (MTM): Participants will receive MTM in addition to the educational materials.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Injurious fall
|
2.3%
1/44 • Number of events 1 • 1 year
|
2.2%
1/46 • Number of events 1 • 1 year
|
|
Infections and infestations
Infections
|
2.3%
1/44 • Number of events 1 • 1 year
|
8.7%
4/46 • Number of events 4 • 1 year
|
|
Cardiac disorders
Major cardiac event
|
4.5%
2/44 • Number of events 2 • 1 year
|
2.2%
1/46 • Number of events 1 • 1 year
|
|
Vascular disorders
Stroke
|
2.3%
1/44 • Number of events 1 • 1 year
|
2.2%
1/46 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
GI emergencies
|
4.5%
2/44 • Number of events 2 • 1 year
|
2.2%
1/46 • Number of events 1 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer
|
2.3%
1/44 • Number of events 1 • 1 year
|
0.00%
0/46 • 1 year
|
|
Injury, poisoning and procedural complications
Surgical complications
|
0.00%
0/44 • 1 year
|
2.2%
1/46 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Car accident
|
2.3%
1/44 • Number of events 1 • 1 year
|
0.00%
0/46 • 1 year
|
Other adverse events
| Measure |
Placebo
n=44 participants at risk
Participants enrolled into this arm will only receive educational materials, but will not receive specific recommendations to make changes to the medications they are taking.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Placebo: Participants will receive educational materials, but will not receive MTM.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
Medication Therapy Management (MTM)
n=46 participants at risk
Participants enrolled into this arm will receive educational materials and will have their medications assessed; recommendations for changes in the medications taken will be made when appropriate.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Medication Therapy Management (MTM): Participants will receive MTM in addition to the educational materials.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
|
|---|---|---|
|
Nervous system disorders
Neurological
|
63.6%
28/44 • Number of events 32 • 1 year
|
63.0%
29/46 • Number of events 34 • 1 year
|
|
Gastrointestinal disorders
GI
|
54.5%
24/44 • Number of events 26 • 1 year
|
58.7%
27/46 • Number of events 27 • 1 year
|
|
Infections and infestations
Infections
|
20.5%
9/44 • Number of events 9 • 1 year
|
15.2%
7/46 • Number of events 8 • 1 year
|
|
Immune system disorders
Allergies
|
2.3%
1/44 • Number of events 1 • 1 year
|
2.2%
1/46 • Number of events 1 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
36.4%
16/44 • Number of events 16 • 1 year
|
45.7%
21/46 • Number of events 22 • 1 year
|
|
Cardiac disorders
Cardiovascular
|
13.6%
6/44 • Number of events 6 • 1 year
|
10.9%
5/46 • Number of events 5 • 1 year
|
|
Renal and urinary disorders
Renal and GU
|
6.8%
3/44 • Number of events 4 • 1 year
|
6.5%
3/46 • Number of events 3 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin
|
6.8%
3/44 • Number of events 3 • 1 year
|
10.9%
5/46 • Number of events 5 • 1 year
|
|
General disorders
Other
|
6.8%
3/44 • Number of events 3 • 1 year
|
6.5%
3/46 • Number of events 3 • 1 year
|
|
Metabolism and nutrition disorders
Metabolic
|
11.4%
5/44 • Number of events 5 • 1 year
|
10.9%
5/46 • Number of events 6 • 1 year
|
|
Eye disorders
Visual
|
6.8%
3/44 • Number of events 3 • 1 year
|
10.9%
5/46 • Number of events 5 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary
|
6.8%
3/44 • Number of events 3 • 1 year
|
2.2%
1/46 • Number of events 1 • 1 year
|
|
Ear and labyrinth disorders
Auditory
|
4.5%
2/44 • Number of events 2 • 1 year
|
2.2%
1/46 • Number of events 1 • 1 year
|
Additional Information
Daniela C Moga MD PhD, Associate Professor
University of Kentucky
Phone: 859-323-9682
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place