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

INtervention for Cognitive Reserve Enhancement in Delaying the Onset of Alzheimer's Symptomatic Expression: The INCREASE Study

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.

Study Overview

• Status: Completed
• Conditions: Dementia; Alzheimer's Disease
• Intervention / Treatment: Other: Placebo; Drug: Scopolamine patch; Other: Medication Therapy Management (MTM)

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 Type: Interventional
• Enrollment (Actual): 90
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 101 years (Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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.	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; Other: Medication Therapy Management (MTM); Participants will receive MTM in addition to the educational materials.; Other Names: Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication Appropriateness Index	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.	change from baseline to end of study, an average of 1 year
Trail Making Test B With the Scopolamine Patch	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.	baseline to end of study, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Reserve: Montreal Cognitive Assessment	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.	change from baseline to end of study, an average of 1 year
Cognitive Reserve: California Verbal Learning Test	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	change from baseline to end of study, an average of 1 year
Perceived Health Status	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 .	change from baseline to end of study, an average of 1 year

Collaborators and Investigators

• Sponsor: Daniela Moga
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Daniela Moga, MD, PhD, University of Kentucky

Publications and helpful links

General Publications

• Moga DC, Beech BF, Abner EL, Schmitt FA, El Khouli RH, Martinez AI, Eckmann L, Huffmyer M, George R, Jicha GA. INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer's Symptomatic Expression (INCREASE), a randomized controlled trial: rationale, study design, and protocol. Trials. 2019 Dec 30;20(1):806. doi: 10.1186/s13063-019-3993-0.
• Moga DC, Abner EL, Schmitt FA, Eckmann L, Huffmyer M, Martinez AI, Beech BF, George R, El Khouli RH, Ali D, Jicha GA. Intervention for Cognitive Reserve Enhancement in Delaying the Onset of Alzheimer's Symptomatic Expression (INCREASE) Study: Results from a Randomized Controlled Study of Medication Therapy Management Targeting a Delay in Prodromal Dementia Symptom Progression. J Prev Alzheimers Dis. 2022;9(4):646-654. doi: 10.14283/jpad.2022.55.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2017
• Primary Completion (Actual): April 21, 2021
• Study Completion (Actual): April 21, 2021

Study Registration Dates

• First Submitted: July 15, 2016
• First Submitted That Met QC Criteria: July 28, 2016
• First Posted (Estimated): July 29, 2016

Study Record Updates

• Last Update Posted (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: deprescribing; medication therapy management
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Antiemetics; Gastrointestinal Agents; Adjuvants, Anesthesia; Mydriatics; Scopolamine; Butylscopolammonium Bromide
• Other Study ID Numbers: 16-0375-F2L INCREASE; 1R01AG054130-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No