A SMART Trial of Adaptive Exercises to Optimize Aerobic-Fitness Responses (SMART)

February 9, 2024 updated by: Arizona State University

Precision Medicine in Alzheimer's Disease: A SMART Trial of Adaptive Exercises and Their Mechanisms of Action Using AT(N) Biomarkers to Optimize Aerobic-Fitness Responses (The FIT-AD SMART Trial)

The goal of this clinical trial is to test 6 months of aerobic exercise in older adults who are 65 years or older and have mild cognitive impairment (MCI) or probable/possible mild Alzheimer's Disease. The main questions it aims to answer are:

  • test the effects of aerobic exercise on aerobic fitness, white matter hyperintensity (WMH) volume, and patient-centered outcomes;
  • identify the best exercise to improve aerobic fitness and reduce non-responses over 6 months; and
  • examines the mechanisms of aerobic exercise's action on memory in older adults with early AD.

Participants will receive 6 months of supervised exercise, undergo cognitive data collection and exercise testing 5 times over a year span, have an MRI brain scan 3 times over a one-year span, and have monthly follow-up discussions on health and wellness.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this Phase II, mechanistic Sequential, Multiple Assignment, Randomized Trial (SMART) is to test the effects of 6-month aerobic exercise on aerobic fitness and MRI and plasma biomarkers in community-dwelling older adults with early Alzheimer's disease (AD). The aims are to (I) test the effects of aerobic exercise on aerobic fitness, white matter hyperintensity (WMH) volume, and patient-centered outcomes; (II) identify the best exercise to improve aerobic fitness and reduce non-responses over 6 months; and (III) examines the mechanisms of aerobic exercise's action on memory in older adults with early AD. This trial builds on our previous work showing inter-individual differences in VO2peak responses to moderate-intensity continuous training (MICT); an ability of plasma neurofilament light chain (NfL) to predict cognition; and 6-month MICT maintained memory, reduced WMH, affected plasma p-tau181, and improved physical function, QoL, and caregiver distress. Aerobic exercise is a promising treatment for Alzheimer's disease (AD) and AD-related dementia (ADRD) but has shown mixed effects on cognition, physical function, behavioral and psychological symptoms of dementia (BPSD), quality of life (QoL), and caregiver burden. These findings are likely due to inter-individual differences in aerobic fitness responses, which have long been established in adults using VO2peak and were first reported in AD/ADRD by our team. Most AD/ADRD exercise trials did not measure VO2peak and those that reported large inter-individual differences in VO2peak responses to MICT. Mechanistically, animal studies support aerobic exercise modifying AD's ATN biomarkers (Amyloid-beta [Aβ], Tau, and Neurodegeneration), but human studies are few and have conflicting findings. Hence, precision exercise is critical to improving VO2peak responses with alternative interventions (high-intensity interval training (HIIT) or combined aerobic & resistance exercise (CARE)). Because VO2peak can improve and peak from 3 months of MICT, 3 months is an ideal time to identify MICT non-responders and initiate HIIT or CARE.

Study Type

Interventional

Enrollment (Estimated)

216

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85004
        • Recruiting
        • Arizona State University
        • Sub-Investigator:
          • Michael Todd, PhD
        • Principal Investigator:
          • Fang Yu, PhD
        • Contact:
        • Sub-Investigator:
          • David Coon, PhD
        • Sub-Investigator:
          • Rodney Joseph, PhD
        • Sub-Investigator:
          • Molly Maxfield, PhD
        • Sub-Investigator:
          • Jeremy Pruzin, MD
        • Sub-Investigator:
          • Yi Su, MD
        • Sub-Investigator:
          • Dereck Salisbury, PhD
        • Sub-Investigator:
          • Danni Li, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Participants:

  • Clinical diagnosis of MCI or probable and possible mild AD dementia according to 2011 Alzheimer's association-NIA criteria.
  • Community-dwelling, e.g., homes and assisted living
  • Age 65 years and older
  • Medical clearance from PCP or cardiovascular provider
  • Have a qualified study partner
  • Agree to the blood draws
  • Verified MRI safety

Study Partner:

  • Age 18 or older
  • Contact with participant ≥ 2 times per week for ≥ 6 months
  • Know the participant's memory status and ability to perform activities of daily living
  • Consent to participant

Exclusion Criteria:

Participants

  • Resting HR ≤ 50 or ≥ 100 beats/min after 5-minutes of quiet resting
  • American College of Sports Medicine contraindications to exercise
  • New, unevaluated symptoms or diseases a healthcare provider has not evaluated
  • Abnormal cardiac condition uncovered during VO2peak testing
  • Enrollment in another intervention that aims at improving cognition
  • Moderate to strenuous exercise ≥150 minutes a week in the previous 6 months
  • ≥ 2 anti-depression medications, or poorly managed or unstable depression
  • Poorly managed or unstable anxiety

Study partners:

  • none

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Moderate Intensity Continuous Training (MICT)
Cycling on recumbent stationary cycle at moderate intensity for 30-50 minutes, 3 times per week for 3-6 months
Behavioral: Moderate Intensity Continuous Training (MICT)
Aerobic cycling at a moderate intensity (50-75% of heart rate reserve) for 30-50 minutes, 3 times per week for 3-6 months.
Other Names:
  • Aerobic exercise
  • Continuous Training
  • Cardio
Sham Comparator: Chair-based Stretch
Stretching at low intensity for 30-50 minutes, 3 times per week for 6 months
Behavioral: Chair-based Stretch
Stretching while seated for 30-50 minutes, 3 times per week for 6 months.
Other Names:
  • Stretch
  • Range of motion
  • flexibility
Active Comparator: High-Intensity Interval Training (HIIT)
MICT for 3 months, and then cycling on recumbent stationary cycle at alternate high and moderate intensity for 40 minutes, 3 times per week for 3 months.
Behavioral: High-Intensity Interval Training (HIIT)
Aerobic cycling at a vigorous intensity (80-90% of heart rate reserve 4-minute bouts with 4-minute recovery intervals) for 40 minutes, 3 times per week for 3 months.
Other Names:
  • HIIT
  • Vigorous training
  • Hard exercise
Active Comparator: Combined Aerobic Resistance Exercise (CARE)
MICT for 3 months, and then cycling on recumbent stationary cycle at moderate intensity for 30 minutes, followed by 20-minute strength-building exercise, 3 times per week for 3 months.
Behavioral: Combined Aerobic Resistance Exercise (CARE)
6 full-body strength-building exercises followed by 30 minutes of MICT cycling (described above). Total duration is 60 minutes, 3 times per week for 3 months.
Other Names:
  • Exercise training
  • CARE
  • Strength and Cardio Training
  • Combination training

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak oxygen consumption
Time Frame: measured at 0 and 6 months
VO2peak will be assessed from the symptom-limited peak cycle-ergometer test
measured at 0 and 6 months
White Matter Hyperintensity volume
Time Frame: measured at 0 and 6 months
WMH will be assessed from MRI.
measured at 0 and 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Memory
Time Frame: measured at 0, 6, and 12 months
Wechsler Memory Scale - Revised; Logical Memory; score 0-50; higher scores indicate less impairment
measured at 0, 6, and 12 months
Physical function
Time Frame: measured at 0, 3, 6, 9, & 12 months
Short Physical Performance Battery: score 0-12; lower scores indicate poorer physical function
measured at 0, 3, 6, 9, & 12 months
Behavioral and psychiatric symptoms of dementia (BPSD)
Time Frame: measured at 1, 3, 6, 9, & 12 months
Neuropsychiatric Inventory Questionnaire; symptoms present, if yes, then severity and caregiver distress are reported.
measured at 1, 3, 6, 9, & 12 months
Caregiver burden
Time Frame: measured at 1, 3, 6, 9, & 12 months
4-item Zarit Burden Interview: score 0-16; higher scores reflect greater burden
measured at 1, 3, 6, 9, & 12 months
Quality of Life (QoL)
Time Frame: measured at 1, 3, 6, 9, & 12 months
Quality of Life - AD: score 0-52; higher scores reflect greater life satisfaction
measured at 1, 3, 6, 9, & 12 months
Blood amyloid-beta 42 and 40
Time Frame: measured at 1, 3, 6, 9, & 12 months
20 mL blood sample collection
measured at 1, 3, 6, 9, & 12 months
Blood phosphorylated tau 181
Time Frame: measured at 1, 3, 6, 9, & 12 months
20 mL blood sample collection
measured at 1, 3, 6, 9, & 12 months
Blood total tau, neurofilament light chain
Time Frame: measured at 1, 3, 6, 9, & 12 months
20 mL blood sample collection
measured at 1, 3, 6, 9, & 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dementia severity
Time Frame: measured at 0, 3, 6, 9, & 12 months
Montreal cognitive Assessment: score 0-30; higher scores reflect less impairment
measured at 0, 3, 6, 9, & 12 months
Executive function
Time Frame: measured at 0, 3, 6, 9, & 12 months
Trail Making Test: number of seconds required to complete the task; therefore, higher scores reveal greater impairment
measured at 0, 3, 6, 9, & 12 months
Visuospatial ability
Time Frame: measured at 0, 3, 6, 9, & 12 months
Benson Complex Figure: score 0-17; higher scores reflect better visuospatial abilities.
measured at 0, 3, 6, 9, & 12 months
Language preservation
Time Frame: measured at 0, 3, 6, 9, & 12 months
Multilingual naming test: count the number of items correctly named; higher counts reflect better language preservation
measured at 0, 3, 6, 9, & 12 months
Fall risk
Time Frame: measured at 0, 3, 6, 9, & 12 months
Timed up and Go: 3-meter course timed; time recorded in seconds; less time reflects lower fall risk
measured at 0, 3, 6, 9, & 12 months
Social interaction
Time Frame: measured at 0, 3, 6, 9, & 12 months
Engagement and Independence in Dementia Questionnaire: Scale - not true at all = 0, rarely true = 1, sometimes true = 2, often true = 3, true nearly all of the time = 4; higher ratings reflect more social interaction
measured at 0, 3, 6, 9, & 12 months
Anxiety
Time Frame: measured at 0, 3, 6, 9, & 12 months
Generalized Anxiety Disorder - 7: 0-21; lower scores reflect less anxiety
measured at 0, 3, 6, 9, & 12 months
Depression
Time Frame: measured at 0, 3, 6, 9, & 12 months
Geriatric Depression Scale: Score 1-15, lowers scores reflect less depression
measured at 0, 3, 6, 9, & 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arizona State University

Collaborators

Banner Alzheimer's Institute

Investigators

  • Principal Investigator: Fang Yu, PhD, Arizona State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 22, 2023

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

April 3, 2023

First Submitted That Met QC Criteria

May 25, 2023

First Posted (Actual)

May 26, 2023

Study Record Updates

Last Update Posted (Estimated)

February 13, 2024

Last Update Submitted That Met QC Criteria

February 9, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00017678

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Investigators will create a de-identified dataset and de-identified bio-samples to share at the time of publishing the primary results of our trial or within 9 months of database lock, whichever comes first. The data to be shared include but not limited to:

  • de-identified health history and covariate scores
  • de-identified instrument item and total scores of primary and secondary outcomes
  • de-identified exercise session report data
  • de-identified bio-samples

IPD Sharing Time Frame

May 2027

IPD Sharing Access Criteria

  • a commitment to using the data only for research purposes and not to identify an individual participant
  • a commitment to securing the data using appropriate computer technology
  • a commitment to destroying or returning the data after analyses are completed
  • all data sharing requests must be reviewed and approved by the PI

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cognitive Impairment

Clinical Trials on Moderate Intensity Continuous Training (MICT)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mexico

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe