NCT03683394: SMARRT

Systematic Multi-domain Alzheimer's Risk Reduction Trial

Completed NA Results posted Last updated 21 September 2023

What this trial tests

NA trial testing SMARRT Intervention in Dementia in 172 participants. Completed in 10 August 2022.

Timeline

30 August 2018

Primary endpoint
10 August 2022

10 August 2022

Quick facts

Lead sponsor	Kaiser Permanente
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	prevention
Enrollment	172
Start date	30 August 2018
Primary completion	10 August 2022
Estimated completion	10 August 2022
Sites	1 location across United States

Drugs / interventions tested

• SMARRT Intervention
• Health Education Intervention

Conditions studied

• Dementia — all drugs for Dementia →
• Alzheimer Disease — all drugs for Alzheimer Disease →

Sponsor

Kaiser Permanente — full company profile →

Who can join

Adults 70 to 89, any sex, with Dementia or Alzheimer Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cognitive Change Primary · 2 Years

Cognitive function will be measured by the modified Neuropsychological Test Battery (mNTB) global score, which is a composite z-score, an average of z-scores from tests of several cognitive domains. The total score is reported. Higher values signify higher cognitive performance. A z-score of 0 represents the population mean. Treatment effects were estimated using linear mixed models (LMMs) for the changes from baseline to each follow-up assessment (6, 12, 18, and 24 months), with average treatment effects (ATEs) estimated by the average of the four visit-specific between-group differences in

Group	Value	95% CI
SMARRT Intervention	0.34	0.25 – 0.42
Health Education Control	0.19	0.11 – 0.26

Change in Targeted Risk Factors Secondary · 2 Years

A composite Z-score for risk factors based on the following: the Rapid Assessment of Physical Activity for Older Adult (RAPA), steps per day averaged over 7 days; blood pressure measures averaged for each six-month period for participants with hypertension; the Pittsburgh Sleep Quality Index (PSQI); use of potentially harmful prescription medications; the Center for Epidemiologic Studies - Depression Scale (CES-D); hemoglobin A1c (HbA1c) values averaged over a 12-month time period; the Patient-Reported Outcomes Measurement Information System (PROMIS) Satisfaction with Social Activities, Short

Group	Value	95% CI
SMARRT Intervention	0.06	-0.01 – 0.13
Health Education Control	-0.05	-0.12 – 0.02

Quality of Life Measure Secondary · 2 Years

Measured with Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health. Higher score indicates better global health and quality of life; range = 0 to 20.

Group	Value	95% CI
SMARRT Intervention	12.69	9.44 – 15.93
Health Education Control	11.58	8.36 – 14.79

Number of Participants With Mild Cognitive Impairment, Alzheimer's Disease, and Dementia Secondary · 2 Years

Number of participants at follow up visits with Mild Cognitive Impairment, Alzheimer's Disease, and/or Dementia or with a low score on the Cognitive Abilities Screening Instrument (CASI) (\<27 consistent with cognitive impairment). Lower score indicates poorer cognition; range is 0-33.

Group	Value	95% CI
SMARRT Intervention	5
Health Education Control	8

Adverse events — posted to ClinicalTrials.gov

Time frame: 24 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

SMARRT Intervention

Serious: 24/82 (29%)

Deaths: 3/82

Health Education Control

Serious: 23/90 (26%)

Deaths: 1/90

Serious adverse events (15 terms)

Reaction	System	SMARRT Intervention	Health Education Control
Hospitalizations	Cardiac disorders	—	—
Hospitalizations	Gastrointestinal disorders	—	—
Hospitalizations	Vascular disorders	—	—
Hospitalizations	Musculoskeletal and connective tissue disorders	—	—
Hospitalizations	Infections and infestations	—	—
Hospitalizations	General disorders	—	—
Hospitalizations	Renal and urinary disorders	—	—
Hospitalizations	Surgical and medical procedures	—	—
Hospitalizations	Blood and lymphatic system disorders	—	—
Hospitalizations	Hepatobiliary disorders	—	—
Hospitalizations	Reproductive system and breast disorders	—	—
Hospitalizations	Respiratory, thoracic and mediastinal disorders	—	—
Life-Threatening Event	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Hospitalizations	Endocrine disorders	—	—
Life-Threatening Event	Cardiac disorders	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	SMARRT Intervention	Health Education Control
Non-Serious, Possibly Related	Musculoskeletal and connective tissue disorders	—	—
Non-Serious, Possibly Related	Psychiatric disorders	—	—
Non-Serious, Possibly Related	Cardiac disorders	—	—
Non-serious, Possibly Related	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Hospitalizations, Hospitalizations, Hospitalizations, Hospitalizations, Hospitalizations, Hospitalizations, Hospitalizations, Hospitalizations.

Data from ClinicalTrials.gov NCT03683394 adverse events section.

Sponsor's own description

The primary goal of this randomized controlled trial (RCT) is to pilot-test a personalized, pragmatic, multi-domain Alzheimer's disease risk reduction intervention in a U.S. integrated healthcare delivery system.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Effect of Personalized Risk-Reduction Strategies on Cognition and Dementia Risk Profile Among Older Adults: The SMARRT Randomized Clinical Trial.
   Yaffe K, Vittinghoff E, Dublin S, Peltz CB, et al · · 2024 · cited 81× · PMID 38010725 · DOI 10.1001/jamainternmed.2023.6279
2. Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT): Study Protocol.
   Yaffe K, Barnes DE, Rosenberg D, Dublin S, et al · · 2019 · cited 33× · PMID 30475764 · DOI 10.3233/jad-180634
3. Canadian Stroke Best Practice Recommendations: Vascular cognitive impairment, 7th edition practice guidelines update, 2024.
   Swartz RH, Longman RS, Lindsay MP, Lund R, et al · · 2025 · cited 12× · PMID 39822128 · DOI 10.1002/alz.14324
4. Engaging Patients to Design the Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT) Intervention: Findings from a Web-Based Survey.
   Marcum ZA, Rosenberg D, Barnes DE, Yaffe K, et al · · 2020 · cited 5× · PMID 32904663 · DOI 10.3233/adr-200210
5. The Systematic Multi-domain Alzheimer's Risk Reduction Trial (SMARRT) intervention: A personalized approach to dementia risk reduction.
   Barnes DE, Balderson BH, Shulman L, Rosenberg DE, et al · · 2024 · cited 2× · PMID 39623940 · DOI 10.1177/13872877241296161
6. The best treatment is prevention: prevention of cognitive decline and dementia - current state, gaps and next steps.
   Reetz K, Liepelt-Scarfone I, Häger A, Flöel A, et al · · 2026 · PMID 42015253 · DOI 10.1186/s42466-026-00494-4
7. The Impact of Lifestyle on Brain Health.
   Potashkin JA, Vidyadhara DJ, Hunsberger HC. · · 2025 · PMID 41480488 · DOI 10.1177/15598276251411888
8. 15th Conference Clinical Trials Alzheimer’s Disease, November 29- December 2, 2022, San Francisco, CA, USA: Symposia - Oral Communications - Late Breaking Abstracts (Clinical Trial Alzheimer’s Disease)
   · 2022