Clinical trial NCT05877196: A SMART Trial of Adaptive Exercises to Optimize Aerobic-Fitness Responses
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mild Cognitive Impairment
Alzheimer Disease
Cognitive Impairment
Cognitive Decline
Memory Loss
Memory Impairment
Lead sponsor: Arizona State University
Sponsor class: OTHER
Collaborators: name: Banner Alzheimer's Institute
First posted: 2023-05-26
Enrollment: 216
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Sequential, Multiple Assignment, Randomized Trial
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak oxygen consumption
timeFrame: measured at 0 and 6 months
measure: White Matter Hyperintensity volume
timeFrame: measured at 0 and 6 months
Secondary outcomes:
measure: Memory
timeFrame: measured at 0, 6, and 12 months
measure: Physical function
timeFrame: measured at 0, 3, 6, 9, & 12 months
measure: Behavioral and psychiatric symptoms of dementia (BPSD)
timeFrame: measured at 1, 3, 6, 9, & 12 months
measure: Caregiver burden
timeFrame: measured at 1, 3, 6, 9, & 12 months
measure: Quality of Life (QoL)
timeFrame: measured at 1, 3, 6, 9, & 12 months
measure: Blood amyloid-beta 42 and 40
timeFrame: measured at 1, 3, 6, 9, & 12 months
measure: Blood phosphorylated tau 181
timeFrame: measured at 1, 3, 6, 9, & 12 months
measure: Blood total tau, neurofilament light chain
timeFrame: measured at 1, 3, 6, 9, & 12 months
Other outcomes:
measure: Dementia severity
timeFrame: measured at 0, 3, 6, 9, & 12 months
measure: Executive function
timeFrame: measured at 0, 3, 6, 9, & 12 months
measure: Visuospatial ability
timeFrame: measured at 0, 3, 6, 9, & 12 months
measure: Language preservation
timeFrame: measured at 0, 3, 6, 9, & 12 months
measure: Fall risk
timeFrame: measured at 0, 3, 6, 9, & 12 months
measure: Social interaction
timeFrame: measured at 0, 3, 6, 9, & 12 months
measure: Anxiety
timeFrame: measured at 0, 3, 6, 9, & 12 months
measure: Depression
timeFrame: measured at 0, 3, 6, 9, & 12 months
Locations:
city: Phoenix
country: United States
facility: Arizona State University
state: Arizona
Study officials:
affiliation: Arizona State University
name: Fang Yu, PhD
role: PRINCIPAL_INVESTIGATOR
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