The INCREASE Study - Delaying the Onset of Alzheimer's Symptomatic Expression

• Sponsor: Daniela Moga (Other)
• Overall Status: Completed
• CT.gov ID: NCT02849639
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 90
• Location: 1
• Arms: 2
• Actual Duration (Months): 48.6
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

The study will examine the impact on cognitive reserve of a pharmacist-physician patient-centered medication therapy management intervention to address inappropriate medication use as identified by the Beers 2015 list. By bolstering cognitive reserve, this project will directly address the National Alzheimer's Project Act 2015 priorities serving to delay onset of symptoms in preclinical dementia. The results of this study will provide valuable insights on how to expand this intervention to reduce the prevalence and associated healthcare costs of symptomatic Alzheimer's disease.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease; Dementia	Other: Placebo; Other: Medication Therapy Management (MTM); Drug: Scopolamine patch	Early Phase 1

Detailed Description

This is a 12-month, parallel arm, study to be conducted at the University of Kentucky. The study will involve assessing medication use and identifying any medicines that may be inappropriate for elderly adults.

At the beginning of the study, participants will be asked to undergo one amyloid-PET scan to detect early amyloid plaques in their brain which could increase the risk of Alzheimer's disease in the near future. In addition, 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.

Part of the study includes collecting information regarding participants memory and thinking abilities. Participants will be asked to complete questionnaires as well as memory and thinking tests.

A study doctor will review participants medical history and then perform routine medical (physical and neurological) examinations.

Two of the study visits will be conducted by phone to check up on the participants.

At the beginning, middle, and end of the study, participants will meet with a doctor and pharmacist to review and make any changes deemed appropriate to their current medicines. This will be done in order to try and eliminate medicines that are not recommended for the elderly. These visits are referred to as the Medication Therapy Management (MTM).

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: INtervention for Cognitive Reserve Enhancement in Delaying the Onset of Alzheimer's Symptomatic Expression: The INCREASE Study
• Actual Study Start Date: Apr 4, 2017
• Actual Primary Completion Date: Apr 21, 2021
• Actual Study Completion Date: Apr 21, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 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.	Other: Placebo; Participants will receive educational materials, but will not receive MTM.; Other Names: Control ; Drug: 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.; Other Names: Scopolamine Challenge
Active Comparator: 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.	Other: Medication Therapy Management (MTM); Participants will receive MTM in addition to the educational materials.; Other Names: Intervention ; Drug: 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.; Other Names: Scopolamine Challenge

Outcome Measures

Primary Outcome Measures

1. Medication Appropriateness Index [change from baseline to end of study, an average of 1 year]

   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.

2. Trail Making Test B With the Scopolamine Patch [baseline to end of study, an average of 1 year]

   End 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.

Secondary Outcome Measures

1. Cognitive Reserve: Montreal Cognitive Assessment [change from baseline to end of study, an average of 1 year]

   Change from baseline to end of study for Montreal Cognitive Assessment. Data analysis is currently underway for this secondary outcome.

2. Cognitive Reserve: California Verbal Learning Test [change from baseline to end of study, an average of 1 year]

   Change from baseline to end of study for California Verbal Learning test. Data analysis is currently underway for this secondary outcome.

3. Perceived Health Status [change from baseline to end of study, an average of 1 year]

   Change from baseline to end of study for Short Form Health Survey (SF-36). Data analysis is currently underway for this secondary outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years to 101 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Non-demented

• No previous reaction or contraindication to scopolamine patch, or medical condition warranting dose adjustment in scopolamine including but not limited to: open angle glaucoma, gastrointestinal or urinary outlet obstructions, seizures, or psychosis.

• No contraindications to Aβ-PET scan including hypersensitivity to PET ligand or radiation exposures in the past year that would exceed the acceptable safe annual exposure in combination with the Aβ PET

• Medically stable and able to complete all study activities, as determined by the investigator

• Reporting at least one potentially inappropriate medication as listed in the Beers 2015 criteria

• Living in the community

• Willing to participate in this intervention study

Exclusion Criteria:

• Allergy or other know intolerance to scopolamine patches

• Narrow-angle glaucoma

• Difficulty swallowing

• Stomach or bowel problems (e.g., blockage, muscle weakness, ulcerative colitis)

• Bleeding

• Acid reflux disease

• Myasthenia gravis

• Blockage of the urinary tract.

• Seizures

• Psychosis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kentucky	Lexington	Kentucky	United States	40536

Sponsors and Collaborators

• Daniela Moga
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Daniela Moga, MD, PhD, University of Kentucky

Study Documents (Full-Text)

• Study Protocol - Feb 27, 2018
• Statistical Analysis Plan - Dec 14, 2015
• Informed Consent Form - Nov 20, 2019

More Information

Publications

None provided.

• Responsible Party: Daniela Moga, Sponsor/PI, University of Kentucky
• ClinicalTrials.gov Identifier: NCT02849639
• Other Study ID Numbers: 16-0375-F2L INCREASE; 1R01AG054130-01
• First Posted: Jul 29, 2016
• Last Update Posted: Aug 22, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Daniela Moga, Sponsor/PI, University of Kentucky: deprescribing; medication therapy management
• Additional relevant MeSH terms: Alzheimer Disease; Scopolamine; Butylscopolammonium Bromide

Study Results

Participant Flow

Arm/Group Title	Placebo	Medication Therapy Management (MTM)
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	44	46
COMPLETED	41	44
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Placebo	Medication Therapy Management (MTM)	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	44	46	90
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.1 (6.6)	73.4 (5.6)	73.9 (6.0)
Sex: Female, Male (Count of Participants)
Female	23 52.3%	34 73.9%	57 63.3%
Male	21 47.7%	12 26.1%	33 36.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	44 100%	46 100%	90 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 4.5%	0 0%	2 2.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 4.5%	6 13%	8 8.9%
White	40 90.9%	40 87%	80 88.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Standardized Uptake Value ratio (Count of Participants)
SUVr<1.2	13 29.5%	14 30.4%	27 30%
1.2<=SUVr<1.4	17 38.6%	17 37%	34 37.8%
SUVr>=1.4	14 31.8%	15 32.6%	29 32.2%
Years of education (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	16.4 (2.6)	16.5 (3.0)	16.5 (2.8)
Total number of medications (medications) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [medications]	12.9 (4.8)	12.7 (5.0)	12.8 (4.8)
Number of medications on 2015 Beers list (medications) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [medications]	2.2 (1.2)	2.5 (1.2)	2.4 (1.2)
Medication appropriateness index (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	10.6 (7.4)	13.5 (9.4)	12.1 (8.5)

Outcome Measures

1. Primary Outcome

Title	Medication Appropriateness Index
Description	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.
Time Frame	change from baseline to end of study, an average of 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Medication Therapy Management (MTM)
Arm/Group Description	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.	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.
Measure Participants	41	44
Least Squares Mean (Standard Error) [units on a scale]	11.2 (0.6)	9.4 (0.6)

2. Primary Outcome

Title	Trail Making Test B With the Scopolamine Patch
Description	End 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.
Time Frame	baseline to end of study, an average of 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Medication Therapy Management (MTM)
Arm/Group Description	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.	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.
Measure Participants	40	42
Least Squares Mean (Standard Error) [z-scores]	-0.1 (0.14)	0.03 (0.14)

3. Secondary Outcome

Title	Cognitive Reserve: Montreal Cognitive Assessment
Description	Change from baseline to end of study for Montreal Cognitive Assessment. Data analysis is currently underway for this secondary outcome.
Time Frame	change from baseline to end of study, an average of 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Cognitive Reserve: California Verbal Learning Test
Description	Change from baseline to end of study for California Verbal Learning test. Data analysis is currently underway for this secondary outcome.
Time Frame	change from baseline to end of study, an average of 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Perceived Health Status
Description	Change from baseline to end of study for Short Form Health Survey (SF-36). Data analysis is currently underway for this secondary outcome.
Time Frame	change from baseline to end of study, an average of 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	1 year
Arm/Group Title	Placebo		Medication Therapy Management (MTM)
Arm/Group Description	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.		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.
All Cause Mortality
	Placebo		Medication Therapy Management (MTM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/44 (4.5%)		0/46 (0%)
Serious Adverse Events
	Placebo		Medication Therapy Management (MTM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/44 (20.5%)		7/46 (15.2%)
Cardiac disorders
Major cardiac event	2/44 (4.5%)	2	1/46 (2.2%)	1
Gastrointestinal disorders
GI emergencies	2/44 (4.5%)	2	1/46 (2.2%)	1
Infections and infestations
Infections	1/44 (2.3%)	1	4/46 (8.7%)	4
Injury, poisoning and procedural complications
Injurious fall	1/44 (2.3%)	1	1/46 (2.2%)	1
Surgical complications	0/44 (0%)	0	1/46 (2.2%)	1
Car accident	1/44 (2.3%)	1	0/46 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer	1/44 (2.3%)	1	0/46 (0%)	0
Vascular disorders
Stroke	1/44 (2.3%)	1	1/46 (2.2%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Medication Therapy Management (MTM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/44 (95.5%)		41/46 (89.1%)
Cardiac disorders
Cardiovascular	6/44 (13.6%)	6	5/46 (10.9%)	5
Ear and labyrinth disorders
Auditory	2/44 (4.5%)	2	1/46 (2.2%)	1
Eye disorders
Visual	3/44 (6.8%)	3	5/46 (10.9%)	5
Gastrointestinal disorders
GI	24/44 (54.5%)	26	27/46 (58.7%)	27
General disorders
Other	3/44 (6.8%)	3	3/46 (6.5%)	3
Immune system disorders
Allergies	1/44 (2.3%)	1	1/46 (2.2%)	1
Infections and infestations
Infections	9/44 (20.5%)	9	7/46 (15.2%)	8
Metabolism and nutrition disorders
Metabolic	5/44 (11.4%)	5	5/46 (10.9%)	6
Musculoskeletal and connective tissue disorders
Musculoskeletal	16/44 (36.4%)	16	21/46 (45.7%)	22
Nervous system disorders
Neurological	28/44 (63.6%)	32	29/46 (63%)	34
Renal and urinary disorders
Renal and GU	3/44 (6.8%)	4	3/46 (6.5%)	3
Respiratory, thoracic and mediastinal disorders
Pulmonary	3/44 (6.8%)	3	1/46 (2.2%)	1
Skin and subcutaneous tissue disorders
Skin	3/44 (6.8%)	3	5/46 (10.9%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.