DementiaR2D2NCT04270474
Reducing Risk of Dementia Through Deprescribing
A study testing Deprescribing of target anticholinergics in people with Dementia and Alzheimer Disease, Late Onset, run by Indiana University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Dementia, Alzheimer Disease, Late Onset
- What is being tested?
- Deprescribing of target anticholinergics
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 344 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 Jul 2020to 29 Jul 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
Who cannot join
- 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").
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Indiana University Health
Indianapolis, Indiana, 46202
Community Health Network Foundation, Inc.
Indianapolis, Indiana, 46256
About this study
Official title: Reducing Risk of Dementia Through Deprescribing (R2D2)
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.
Read the 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. Two groups will be recruited: providers (physicians and advanced practice providers including nurse practitioners), and patients. Primary care providers of those prescribed eligible anticholinergic medications will be recruited for participation in the study, and their patients who also meet eligible criteria will be subsequently approached and recruited. 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 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.
- Conditions
- Dementia, Alzheimer Disease, Late Onset
- Being tested
- Deprescribing of target anticholinergics, Usual Care
- Keywords
- deprescribing, anticholinergics, dementia, cognition
- Medical subject headings
- Dementia, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deprescribing of target anticholinergicsOther
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.
Usual CareOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Active Intervention (ACT) | Experimental | Pharmacist-based Deprescribing Receives: Other: Deprescribing of target anticholinergics |
| Usual Care (UC) | Sham comparator | Usual Care Receives: Other: Usual Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline, 6, 12, 18, and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2020
- Study start20 Jul 2020
- Primary completion29 Jul 2026
- Study completion29 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DementiaStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 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.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 344 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA), Regenstrief Institute, Inc.
- Responsible party
- Principal investigator, Noll Campbell, Indiana University
- Investigators
- Noll L Campbell, PharmD, MS, Principal investigator, Indiana University/Purdue University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04270474
- Sponsor's protocol ID
- 1706800075
- Other IDs
- R01AG061452
- Acronym
- R2D2
- Status last verified
- Jul 2026
- First submitted
- 10 Feb 2020
- Last updated
- 3 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data collected through this trial will be made available to either advance scientific research in a way that is allowed by the federal regulations that protect research subjects, or for the purpose of auditing or program evaluation by the government or funding agency. Data sharing for scientific purposes is essential for further translation of research results into knowledge, products, and procedures to improve human health. To protect participants' rights and confidentiality, protected health information will be limited to the minimum necessary for authorized oversight before the data are shared.The final dataset will include demographic, clinical, and limited genetic data. The final subject-level, de-identified dataset will be made available to qualified individuals within the scientific community.
Publications
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.
PubMed 39578926
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reducing Risk of Dementia Through Deprescribing (R2D2)
- ClinicalTrials.gov ID
- NCT04270474
- Acronym / sponsor ID
- R2D2 / 1706800075
- Conditions
- Dementia, Alzheimer Disease, Late Onset
- Keywords
- deprescribing, anticholinergics, dementia, cognition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 344 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA), Regenstrief Institute, Inc.
- Study start
- 20 Jul 2020 (actual)
- Primary completion
- 29 Jul 2026 (actual)
- Study completion
- 29 Jul 2026 (actual)
- First posted
- 17 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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. Two groups will be recruited: providers (physicians and advanced practice providers including nurse practitioners), and patients. Primary care providers of those prescribed eligible anticholinergic medications will be recruited for participation in the study, and their patients who also meet eligible criteria will be subsequently approached and recruited. 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 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- 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. Study outcomes will be collected directly from participants; no outcomes will be collected from physicians.
| Arm | Type | Receives |
|---|---|---|
| Active Intervention (ACT) | Experimental | Other: Deprescribing of target anticholinergicsPharmacist-based Deprescribing |
| Usual Care (UC) | Sham comparator | Other: Usual CareUsual Care |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Deprescribing of target anticholinergicsThe 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. | Other | Active Intervention (ACT) |
| Usual CareThose 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. | Other | Usual Care (UC) |
Primary outcome
Change in Cognitive Composite Score
Time frame: Baseline, 6, 12, 18, and 24 months
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.
Change in Patient Reported Outcome Measurement Information System (PROMIS)
Time frame: Baseline, 6, 12, 18, and 24 months
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.
Change in Health Utilities Index (HUI)
Time frame: Baseline, 6, 12, 18, and 24 months
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2026.
- Derived from this study: PubMed 39578926Campbell 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.
- Individual participant dataSharing planned: Yes. Data collected through this trial will be made available to either advance scientific research in a way that is allowed by the federal regulations that protect research subjects, or for the purpose of auditing or program evaluation by the government or funding agency. Data sharing for scientific purposes is essential for further translation of research results into knowledge, products, and procedures to improve human health. To protect participants' rights and confidentiality, protected health information will be limited to the minimum necessary for authorized oversight before the data are shared.The final dataset will include demographic, clinical, and limited genetic data. The final subject-level, de-identified dataset will be made available to qualified individuals within the scientific community.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Noll L Campbell, PharmD, MS principal investigator
Indiana University/Purdue University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Deprescribing of target anticholinergics in people with Dementia and Alzheimer Disease, Late Onset, 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 5 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 3 Aug 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Cognitive Composite Score (time frame: Baseline, 6, 12, 18, and 24 months). The study lists 3 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 NCT04270474, which also lists 1 linked publication.
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 3 Aug 2026.