R2D2: Reducing Risk of Dementia Through Deprescribing

Sponsor

Indiana University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04270474

Collaborator

National Institute on Aging (NIA) (NIH)

344

Enrollment

Locations

Arms

44.4

Anticipated Duration (Months)

172

Patients Per Site

3.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Dementia Alzheimer Disease, Late Onset	Other: Deprescribing of target anticholinergics Other: Usual Care	N/A

Detailed Description

The R2D2 study will test whether the adverse cognitive effects of anticholinergic medications are reversible by implementing a pharmacist-based deprescribing intervention for older adults within primary care practices. Participants will be randomized to one of two groups: the deprescribing intervention group or usual care; the intervention group will receive a pharmacist-based deprescribing intervention, while the usual care group will receive care as usually provided by their primary and/or specialty care providers. The target population will be primary care older adults with subjective cognitive decline or make at least one error on a cognitive screening test, but do not have dementia, and are currently using a strong anticholinergic medication. The intervention and follow-up data collection will occur over 24 months in order to test the long-term impact of the intervention on the planned clinical outcomes. Study outcomes include cognition (primary) and safety (secondary) through validated self-reported scales.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

344 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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.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.

Masking:

Double (Investigator, Outcomes Assessor)

Masking Description:

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.

Primary Purpose:

Prevention

Official Title:

Reducing Risk of Dementia Through Deprescribing (R2D2)

Actual Study Start Date :

Jul 20, 2020

Anticipated Primary Completion Date :

Mar 31, 2024

Anticipated Study Completion Date :

Mar 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Intervention (ACT) Pharmacist-based Deprescribing	Other: Deprescribing of target anticholinergics 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.
Sham Comparator: Usual Care (UC) Usual Care	Other: Usual Care 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.

Arm

Intervention/Treatment

Experimental: Active Intervention (ACT)

Pharmacist-based Deprescribing

Other: Deprescribing of target anticholinergics

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.

Sham Comparator: Usual Care (UC)

Usual Care

Other: Usual Care

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.

Outcome Measures

Primary Outcome Measures

Change in Cognitive Composite Score [Baseline, 6, 12, 18, and 24 months]
Cognitive composite scores will be collected 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.
Change in Patient Reported Outcome Measurement Information System (PROMIS) [Baseline, 6, 12, 18, and 24 months]
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.
Change in Health Utilities Index (HUI) [Baseline, 6, 12, 18, and 24 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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").