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Alzheimer DiseaseNCT04121858

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

A study testing Brain Safe App in people with Alzheimer Disease and Dementia, run by Indiana University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Alzheimer Disease, Dementia
What is being tested?
Brain Safe App
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
706 participants
Where
2 sitesUnited States
Study dates
16 Oct 2019to 27 Feb 2025
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 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
Show all 9Show fewer
  • Not cognitively impaired
  • Not terminally ill
  • Not sensory impaired (after correction)

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Indiana University

    Indianapolis, Indiana, 46202

  • IU Health

    Indianapolis, Indiana, 46202

Other trials in United States

About this study

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.

Read the 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.

Being tested
Brain Safe App, Attention Control App
Keywords
anticholinergic, cognitive function, brain, aging
Medical subject headings
Alzheimer Disease, Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Brain Safe AppOther

    The Brain Safe app includes the medication list, a personalized risk calculator, multimedia educational content, and a conversation starter/doctor's report.

  • Attention Control AppOther

    The attention control app, called Med Safe, includes only the medication list feature.

Study groups in NCT04121858
Study groupRoleWhat they receive
Brain Safe AppExperimental1)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.
Receives: Other: Brain Safe App
Attention Control AppSham comparator1) 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.
Receives: Other: Attention Control App

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Total Standardized Daily Dose (TSDD) - From Medical Records

    To calculate the Total Standardized Daily Dose (TSDD), we first calculated the Standardized Daily Dose (SDD) for each anticholinergic medication with an ACB Score of 2 or 3. SDD was calculated by multiplying the strength by the units per dose and frequency per day and number of refills. The product was divided by the minimum effective daily dose (where available) or the minimum effective geriatric dose to standardize the quantity across multiple classes of medications. The SDD for all anticholinergics with an ACB score 2 or 3 was then summed for each participant for each 6-month period, and divided by the number of days in the relevant six month period to arrive at a TSDD.

    Range: The minimum possible value is 0 (optimal outcome; indicating zero exposure to ACB 2 or 3 medications). There is no fixed theoretical maximum score(higher value more exposure), as the upper limit is mathematically determined by the total volume and combination of medications a participant is prescribed.

    Measured: Baseline, 6 months, 12 Months

  2. Log Transformed Total Standardized Daily Dose (TSDD) - From Medical Records

    Construct: Measures natural log-transformed average daily exposure to medications with an Anticholinergic Cognitive Burden (ACB) score of 2 or 3 to normalize data distribution.How Computed: Medication Standardized Daily Dose (SDD) = (strength × units/dose × frequency/day × refills) / minimum effective daily or geriatric dose. The SDD for all eligible drugs is summed over 6 months, divided by the number of days in that period to find raw TSDD, and natural log-transformed ($\ln(x+1)$ or similar) for the final score.Scale Range: Minimum value is 0 (representing 0 raw TSDD, or zero exposure). There is no fixed theoretical maximum, as it is mathematically determined by the volume of medications prescribed.Interpretation: A value of 0 is the optimal outcome (no exposure). Higher values represent greater exposure (worse outcome).

    Measured: Baseline, 6, and 12 Months

Secondary outcomes (8)
  1. Overall Cognitive Score

    An overall cognitive score evaluating three domains: memory/new learning, executive function, and processing speed. Calculated by taking the mean of standardized Z-scores from the following specific tests: Hopkins Verbal Learning Test-Revised (HVLT-R) total and delayed recall; Trail Making Test Parts A and B; Phonetic Fluency; Semantic Fluency (adjusted); and Symbol Digit Modalities Test (correct).

    A Z-score of 0 represents the baseline study population mean.

    Standardized scores theoretically range from -3.0 to +3.0. Higher positive Z-scores (standard deviations above the mean) represent better cognitive performance (better outcome). Lower negative Z-scores represent worse cognitive performance (worse outcome). No clinical threshold is defined. Z-scores were derived using baseline means, with timed tests (e.g., Trails) inverted prior to averaging so higher always means better performance.

    Measured: Baseline, 6 months, and 12 months

  2. Choice Reaction Time (CRT)

    Computer-based assessment of Choice Reaction Time (CRT). It is used to evaluate executive function, attention, and psychomotor speed by measuring the time elapsed between the presentation of one of multiple possible stimuli and the participant's correct response.

    The final score represents the average response time (in milliseconds/seconds) across all valid test trials.

    The minimum value is 0. There is no fixed theoretical maximum, as the upper limit is bounded only by the participant's maximum delay.

    Lower values represent faster reaction times, indicating better executive functioning and psychomotor speed (a better outcome). Higher values indicate slower reaction times (a worse outcome).

    Measured: Baseline

  3. Health Utilities Index (HUI) Mark 3

    The Health Utilities Index Mark 3 (HUI3) is a self-reported, multi-attribute health status classification system used to measure overall health-related quality of life and functional capacity.

    The score is calculated using responses across eight dimensions of health (vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain). These subscales are combined using a mathematically weighted scoring algorithm to compute a single total utility index score.

    The total utility score ranges from a minimum of -0.36 (representing a health state considered worse than death) to a maximum of 1.00 (representing perfect health). A score of 0.00 represents death.

    Higher values represent a better health-related quality of life (a better outcome). Lower values represent worse health status (a worse outcome).

    Measured: Baseline, 6 months, and 12 months

  4. Hopkins Verbal Learning Test (HVLT) Total Recall

    Hopkins Verbal Learning Test (HVLT) Total Recall. It is a paper-based list learning and recall assessment used to evaluate verbal memory and new learning capacity.

    Participants are read a list of 12 words and asked to freely recall as many as possible across three consecutive learning trials. The total recall score is calculated by summing the number of correctly recalled words across all three trials.

    The total recall score ranges from a minimum of 0 to a maximum of 36.

    Higher values represent a greater number of words correctly recalled, indicating better memory and verbal learning function (a better outcome). Lower scores indicate worse memory function (a worse outcome).

    Measured: Baseline, 6 months, and 12 months

  5. Hopkins Verbal Learning Test (HVLT) Delayed Recall

    Hopkins Verbal Learning Test (HVLT) Delayed Recall. It is a paper-based assessment used to evaluate delayed verbal memory retention and recall capacity.

    After a standard delay interval (typically 20 to 25 minutes) following the initial learning trials, participants are asked to freely recall the original list of 12 words. The delayed recall score is the total number of words correctly recalled from memory.

    The score ranges from a minimum of 0 to a maximum of 12.

    Higher values represent a greater number of words retained and recalled after the delay, indicating better memory retention (a better outcome). Lower scores indicate worse memory retention (a worse outcome).

    Measured: Baseline, 6 months, 12 months

  6. Trail Making Test (TMT) Parts A

    Number Correct Line Segments. This is a performance-based metric derived from the Trail Making Test (TMT) used to assess visual search, scanning, processing speed, and executive function, particularly when a participant is unable to complete the full timed test.

    The score is calculated by counting the total number of correct line segments a participant successfully draws connecting the sequences of encircled numbers (or numbers and letters) within the allotted test parameters.

    The score ranges from a minimum of 0 to a maximum of 25.

    Higher values represent a greater number of correctly drawn segments, indicating better cognitive processing speed and executive functioning (a better outcome). Lower values indicate worse cognitive performance (a worse outcome).

    Measured: Baseline, 6 months, and 12 months

  7. Trail Making Test (TMT) Parts B

    Number Correct Line Segments (TMT Part B). This is a performance-based metric derived from the Trail Making Test Part B used to assess executive function, cognitive flexibility, and visual-motor tracking. It is particularly useful for quantifying performance when a participant is unable to complete the full timed test.

    The score is calculated by counting the total number of correct line segments a participant successfully draws connecting the 25 encircled numbers and letters in an alternating sequence (1, A, 2, B, 3, C...) within the allotted test parameters.

    The score ranges from a minimum of 0 to a maximum of 25.

    Higher values represent a greater number of correctly drawn segments, indicating better cognitive flexibility and executive functioning (a better outcome). Lower values indicate worse cognitive performance (a worse outcome).

    Measured: Baseline, 6 months, and 12 months

  8. Digit-Symbol Substitution Test (DSST) Number of Correct Responses

    Digit-Symbol Substitution Test (DSST), utilizing the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding subtest. It is a paper-based assessment used to evaluate processing speed, visual-motor coordination, and sustained attention.

    Participants are provided a key pairing numbers (1 through 9) with simple geometric symbols. They are given a strict time limit (120 seconds) to draw the correct corresponding symbols beneath a series of randomized numbers. The final score is the total number of correctly drawn symbols within the time limit.

    The score ranges from a minimum of 0 to a maximum of 135 (the maximum possible items on the WAIS-IV Coding form).

    Higher values represent a greater number of correctly matched symbols, indicating faster processing speed and better cognitive performance (a better outcome). Lower scores indicate slower processing speed (a worse outcome).

    Measured: Baseline, 6 months, and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Oct 2019
  2. Study start16 Oct 2019
  3. Primary completion27 Feb 2025
  4. Study completion27 Feb 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Double blind
Who is masked
Investigator, Outcomes assessor
Enrolment
706 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04121858
Sponsor's protocol ID
1811254189
Other IDs
R01AG056926
Status last verified
May 2026
First submitted
2 Oct 2019
Last updated
20 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: There is no plan to make individual participant data (IPD) available to other researchers

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.

    PubMed 33773639
  • 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.

    PubMed 33606655

Questions about this trial

What is this clinical trial studying?

A study testing Brain Safe App in people with Alzheimer Disease and Dementia, run by Indiana University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Total Standardized Daily Dose (TSDD) - From Medical Records (time frame: Baseline, 6 months, 12 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04121858, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026.

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