Reducing Risk of Dementia Through Deprescribing

NCT04270474 | Active Not Recruiting DMC

• 2 other identifiers: 1706800075R01AG061452
• Study Type: interventional
• Target: 344
• Locations: 1 country
• Sites: 2

Brief Summary

A cluster-randomized controlled trial (RCT) called "Reducing Risk of Dementia through Deprescribing" (R2D2) to evaluate the impact of a deprescribing intervention on important cognitive and safety outcomes.

Conditions

Dementia; Alzheimer Disease, Late Onset

Keywords

deprescribing; anticholinergics; dementia; cognition

Outcome Measures

Primary Outcomes (3)

• Change in Cognitive Composite Score

  Cognitive composite scores will be collected from participants at baseline, 6, 12, 18 and 24 months and changes in the composite scores over time will be compared between the intervention and usual care groups. An overall cognitive composite score including measures of information processing speed, memory, and executive function will be conducted at each time point from the average of each measure's z-score, constructed by subtracting the mean baseline scores and dividing by the baseline standard deviation. The z-score transformation of the cognitive composite score will have a mean of 0 and standard deviation of 1 at baseline, with higher scores representing improvement in cognition.

  Baseline, 6, 12, 18, and 24 months

• Change in Patient Reported Outcome Measurement Information System (PROMIS)

  Participant self-reported, 4-item scales evaluating depression, anxiety, pain, and insomnia will be collected for each participant at each time point. Each PROMIS measure raw score can be converted to a T-score where 50 represents the general population norm for that symptom and each 10-point deviation represents one standard deviation (SD) from the population norm. Changes in the T-scores over time will be compared between the intervention and usual care groups.

  Baseline, 6, 12, 18, and 24 months

• Change in Health Utilities Index (HUI)

  Participant self-reported measure of health-related quality of life, evaluating domains including vision, hearing, speech, ambulation, dexterity, emotion, cognitive function and pain. These attributes produce a single score on a standardized utility measure with individual health domain scores ranging from 0.00 (maximum impairment) to 1.00 (no impairment) and the multi-attribute (HUI) scores ranging from 0.36 to 1.00 with anchors 0.00 = dead and 1.00 = perfect health. HUI scores will be collected at each outcome assessment and change in HUI scores over time will be compared between the intervention and usual care groups.

  Baseline, 6, 12, 18, and 24 months

Study Arms (2)

Active Intervention (ACT)

EXPERIMENTAL

Pharmacist-based Deprescribing

Other: Deprescribing of target anticholinergics

Usual Care (UC)

SHAM COMPARATOR

Usual Care

Other: Usual Care

Interventions

Deprescribing of target anticholinergics OTHER

The active intervention group (ACT) will receive a pharmacist-based deprescribing intervention focused only on targeted anticholinergic medications. The intervention pharmacist will serve as the central source of communication between participants, providers, and (as needed) dispensing pharmacy to coordinate the deprescribing process. The study pharmacists will navigate a shared-decision model between the physicians and participant in order to personalize the selection of appropriate alternatives and switch/titration schedules. Importantly, the pharmacist will supervise the titration and deprescribing plan and communicate with both participants and physicians throughout the study.

Active Intervention (ACT)

Usual Care OTHER

Those in the usual care group will not have access to the study intervention, but will receive a one-time information packet through the mail reviewing risks of polypharmacy, but no information specific to anticholinergic medications. They will receive clinical care as usually provided by their primary care or specialty care physicians.

Usual Care (UC)

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 65 and older;
• At least one office visit to their primary care physician within the previous 12 months;
• Use of a target anticholinergic medication within the last two weeks OR medical record evidence of exposure to target anticholinergic medications at or above a cognitive risk threshold in the prior 12 months
• Able to communicate in English;
• Access to a telephone

You may not qualify if:

• Permanent resident of an extended care facility (nursing home)
• Diagnosis of schizophrenia, bipolar disorder, or schizoaffective disorder defined by International Classification of Diseases (ICD) version 9/10 codes
• Diagnosis of Alzheimer's Disease or Related Dementia as determined by (a), (b), or (c) below:
• ICD-9/10 codes, or
• Current use of a medication for Alzheimer's Disease or a Related Dementia, or
• A pattern of responses to the Functional Activities Questionnaire (FAQ) that indicate dementia (i.e., ≥ 3 FAQ items are scored at "requires assistance," or if ≥ 1 FAQ item is scored at "dependent").

Sponsors & Collaborators

• Indiana University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

Community Health Network Foundation, Inc.

Indianapolis, Indiana, 46256, United States

Location

Related Publications (1)

• Campbell NL, Holden RJ, Gao S, Unverzagt FW, Lane KA, Carter A, Harrington AB, Manoharan S, Manoharan N, Rosenthal DL, Pitts C, Pelkey K, Papineau E, Lauck DM, Keshk N, Alamer K, Khalil H, Boustani MA. Deprescribing anticholinergics to preserve brain health: reducing the risk of dementia through deprescribing (R2D2): study protocol for a randomized clinical trial. Trials. 2024 Nov 22;25(1):788. doi: 10.1186/s13063-024-08618-4.

  PMID: 39578926 DERIVED

MeSH Terms

Conditions

Dementia; Alzheimer Disease

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases

Study Officials

• Noll L Campbell, PharmD, MS

  Indiana University/Purdue University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The principle investigator and all outcome assessor will be blinded to the arm assignment of the subjects. No access to unblinded data will be provided to blinded staff.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adjunct Assistant Professor

Model Details: This cluster-randomized trial will randomize at the level of physicians. Physicians agreeing to participate in the trial will be randomized to intervention or usual care in blocks of two or four. Physician randomization status will determine participants' study group. Physicians randomized to usual care will not have access to the intervention. Study outcomes will be collected directly from participants; no outcomes will be collected from physicians.

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 17, 2020
• Study Start: July 20, 2020
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: The final data set will be made available no later than 9 months of the database lock or at the time of on-line publication of the primary results, whichever comes first.
• Access Criteria: We anticipated access to the study data will be facilitated in collaboration with the Global Alzheimer's Association Interactive Network (GAAIN). As a GAAIN Data Partner, data from this study will be shared in aggregate through the GAAIN portal (gaain.org). GAAIN provides a global infrastructure for cooperative research by linking data repositories that have collected information from participants who are at risk for or have been diagnosed with Alzheimer's disease. The GAAIN network allows the investigator to retain ownership of the data collected in each study, and can detach the data at any time. Only de-identified data is shared with GAAIN or any other research entity.

Locations

US (2)