Brain Safe: Consumer Intervention to Reduce Exposure to Drugs Linked to Alzheimer's Disease

This study is an RCT to evaluate the effectiveness of Brain Safe on reducing anticholinergic exposure. Over 42 months, the trial will enroll 700 community-dwelling older adults who were prescribed one or more strong anticholinergics. Participants will be randomized to use the Brain Safe app or an attention control medication list app for 12 months, with monthly usage reminders.

Study Overview

• Status: Recruiting
• Conditions: Dementia; Alzheimer Disease
• Intervention / Treatment: Other: Brain Safe App; Other: Attention Control App

Detailed Description

This study is a randomized clinical trial (RCT) of the efficacy of a direct-to-consumer intervention called Brain Safe to primarily reduce older adults' exposure to prescription anticholinergics and secondarily improve cognitive function and health-related quality of life. Over 42 months, the trial will enroll 700 community-dwelling older adults who were prescribed one or more strong anticholinergics. Participants will be randomized to use the Brain Safe app or an attention control medication list app for 12 months, with monthly usage reminders.

The primary objective is to test the effect of Brain Safe on anticholinergic exposure at 12 months. We hypothesize that anticholinergic exposure will be lower among those randomized to the Brain Safe intervention compared to those randomized to the attention control app at 12 months. Our primary, powered outcome is the total standard daily dose (TSDD) measure of anticholinergic exposure at 12 months, which is calculated over the preceding 6 months of prescription data. We will electronically capture prescription data monthly and compute TSDD at baseline, 6, and 12 months.

The secondary objective is to test the effect of Brain Safe on: (a) cognitive function and (b) health-related quality of life at 12 months. We hypothesize older adults randomized to Brain Safe will have higher (a) cognitive function, measured by using an objective, performance-based composite, and (b) health-related quality of life (HRQOL), compared to those randomized to the attention control app, at 12 months.

Exploratory objectives are to test the effect of Brain Safe on anticholinergic exposure, cognitive function, and HRQOL at 6 months. This aim will explore the presence of early effects of Brain Safe at 6 months.

• Study Type: Interventional
• Enrollment (Estimated): 700
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Christian Vallejo, BS; Phone Number: 317-274-9212; Email: cvallej@regenstrief.org
• Study Contact Backup: Name: Kimberly Trowbridge; Phone Number: 317-274-9314; Email: kisutrow@regenstrief.org

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • IU Health
      • Contact: Jose Azar, MD
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Richard John Holden
      • Contact: Richard J Holden, PhD; Phone Number: 317-278-5323; Email: rjholden@iu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 1 primary care visit at Eskenazi Health or IU Health in past 12 months
• Age ≥ 60 years
• Written informed consent and HIPAA authorization for the release of personal health information.
• English-speaking
• At least one prescription for a strong anticholinergic medication with Anticholinergic Cognitive Burden (ACB) score 2 or 3 in prior 12 months, and currently using it
• Community-dwelling in Central Indiana
• Not cognitively impaired
• Not terminally ill
• Not sensory impaired (after correction)

Exclusion Criteria:

• Permanent resident of an extended care facility (nursing home); independent or assisted senior care living is allowed if managing own medications.
• Diagnosis of Alzheimer's disease or related dementia (ADRD), determined by International Classification of Diseases (ICD)-9/ICD-10 codes or current use of a medication for ADRD
• Diagnosis of schizophrenia, bipolar disorder, or schizoaffective disorder defined by ICD-9/ICD-10 codes
• Involvement in another clinical trial that would prevent or interfere with study objectives
• Sensory or other impairment prohibiting the use of a mobile touchscreen device or other study activity (after correction)
• Not currently using anticholinergic medication

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
Experimental: Brain Safe App; 1)Brain Safe App provides conversation starters for older adult patients on target anticholinergics. The conversation starters assist the patient to have discussions with their physicians regarding reduction in exposure to prescription anticholinergics. 2) Provides anticholinergic risk assessment.	Other: Brain Safe App; The Brain Safe app includes the medication list, a personalized risk calculator, multimedia educational content, and a conversation starter/doctor's report.
Sham Comparator: Attention Control App; 1) Attention Control App provides a medication list for older patients to use but lacks the conversation starters for patient to use with there physicians aimed at reduction in exposure to prescription anticholinergics.2) No anticholinergic risk assessment.	Other: Attention Control App; The attention control app, called Med Safe, includes only the medication list feature.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total standardized daily dose (TSDD) - from medical records	Total standardized daily dose (TSDD), the cumulative anticholinergic burden computed from medical record medication data over the prior 6 months	12 months
Total standardized daily dose (TSDD) - self-report medication inventory	Total standardized daily dose (TSDD), the cumulative anticholinergic burden computed from self-reported medication inventory data in the Brain Safe or attention control app	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Choice reaction time (CRT)	Computer-based assessment of choice reaction time (CRT), used with simple reaction time (SRT) to assess executive function	12 months
Simple Reaction Time (SRT)	Computer-based test, used with Choice Reaction Time (CRT) test to compute a score, to assess executive function	12 months
Digit-Symbol Substitution Test (DSST)	Paper-based digit-symbol substitution test, from WAIS-IV ( Wechsler Adult Intelligence Scale-IV) Coding, used to assess processing speed	12 months
Hopkins Verbal Learning Test (HVLT)	Paper-based list learning and recall test, used to assess memory.	12 months
Trail Making Test (TMT) Parts A and B	Paper-based test, used to assess executive function	12 months
Health Utilities Index (HUI) Mark 3	Self-reported measure of health-related quality of life, producing a single score on a standardized utility values range from -0.36 for the HUI-3, respectively, to 1.00 with higher scores indicating better outcome	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication perceptions	9-item standardized survey of medication perceptions; developed in-house based on combination of Health Belief Model questionnaires and revised Patients' Attitudes Towards Deprescribing Questionnaire; responses on 5-point agreement scale from strongly agree to strongly disagree, items analyzed separately and as subscale averages (range 1-5, higher indicating more disagreement/less agreement)	12 months
Self-reported deprescribing behavior	4-item standardized survey of self-reported deprescribing behaviors, developed in-house, responses on 5-point agreement scale from strongly agree to strongly disagree, items analyzed separately (range 1-5, higher indicating more disagreement/less agreement)	12 months
System Usability Scale	10-item standardized survey of user-reported technology usability, based on revised System Usability Scale, with scale score computed ranging from 0-100, with 100 indicating highest possible perceived usability	12 months
Satisfaction with technology: 3-item standardized survey	3-item standardized survey of user-reported satisfaction with technology, based on satisfaction items from Technology Acceptance Model questionnaires, responses on 5-point agreement scale from strongly agree to strongly disagree, items analyzed separately and as scale average (range 1-5, higher indicating more disagreement/less agreement)	12 months
Technology use	Usage logs of technology use over time	12 months

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Richard J Holden, PhD, Indiana University School of Medicine

Publications and helpful links

General Publications

• Abebe E, Campbell NL, Clark DO, Tu W, Hill JR, Harrington AB, O'Neal G, Trowbridge KS, Vallejo C, Yang Z, Bo N, Knight A, Alamer KA, Carter A, Valenzuela R, Adeoye P, Boustani MA, Holden RJ. Reducing anticholinergic medication exposure among older adults using consumer technology: Protocol for a randomized clinical trial. Res Social Adm Pharm. 2021 May;17(5):986-992. doi: 10.1016/j.sapharm.2020.10.010. Epub 2020 Oct 22.
• Hill JR, Harrington AB, Adeoye P, Campbell NL, Holden RJ. Going Remote-Demonstration and Evaluation of Remote Technology Delivery and Usability Assessment With Older Adults: Survey Study. JMIR Mhealth Uhealth. 2021 Mar 4;9(3):e26702. doi: 10.2196/26702.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2019
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: October 2, 2019
• First Submitted That Met QC Criteria: October 9, 2019
• First Posted (Actual): October 10, 2019

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: cognitive function; aging; brain; anticholinergic
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 1811254189; R01AG056926 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make individual participant data (IPD) available to other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No