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

Alzheimer Disease Clinical Trial

— SMART  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05877196
• Other study ID #: STUDY00017678
• Status: Recruiting
• Phase: N/A
• Start date: June 22, 2023
• Est. completion date: June 30, 2028

Study information

• Verified date: February 2024
• Source: Arizona State University
• Contact: Hector Cervantes, MS
• Phone: 602-496-2292
• Email: hcervant[@]asu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 216
• Est. completion date: June 30, 2028
• Est. primary completion date: April 1, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Decline
• Cognitive Dysfunction
• Cognitive Impairment
• Memory Disorders
• Memory Impairment
• Memory Loss
• Mild Cognitive Impairment

Intervention

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.
• Chair-based Stretch
Stretching while seated for 30-50 minutes, 3 times per week for 6 months.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Arizona State University	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Arizona State University	Banner Alzheimer's Institute

Country where clinical trial is conducted

United States, 

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* Note: There are 52 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Dementia severity	Montreal cognitive Assessment: score 0-30; higher scores reflect less impairment	measured at 0, 3, 6, 9, & 12 months
Other	Executive function	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
Other	Visuospatial ability	Benson Complex Figure: score 0-17; higher scores reflect better visuospatial abilities.	measured at 0, 3, 6, 9, & 12 months
Other	Language preservation	Multilingual naming test: count the number of items correctly named; higher counts reflect better language preservation	measured at 0, 3, 6, 9, & 12 months
Other	Fall risk	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
Other	Social interaction	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
Other	Anxiety	Generalized Anxiety Disorder - 7: 0-21; lower scores reflect less anxiety	measured at 0, 3, 6, 9, & 12 months
Other	Depression	Geriatric Depression Scale: Score 1-15, lowers scores reflect less depression	measured at 0, 3, 6, 9, & 12 months
Primary	Peak oxygen consumption	VO2peak will be assessed from the symptom-limited peak cycle-ergometer test	measured at 0 and 6 months
Primary	White Matter Hyperintensity volume	WMH will be assessed from MRI.	measured at 0 and 6 months
Secondary	Memory	Wechsler Memory Scale - Revised; Logical Memory; score 0-50; higher scores indicate less impairment	measured at 0, 6, and 12 months
Secondary	Physical function	Short Physical Performance Battery: score 0-12; lower scores indicate poorer physical function	measured at 0, 3, 6, 9, & 12 months
Secondary	Behavioral and psychiatric symptoms of dementia (BPSD)	Neuropsychiatric Inventory Questionnaire; symptoms present, if yes, then severity and caregiver distress are reported.	measured at 1, 3, 6, 9, & 12 months
Secondary	Caregiver burden	4-item Zarit Burden Interview: score 0-16; higher scores reflect greater burden	measured at 1, 3, 6, 9, & 12 months
Secondary	Quality of Life (QoL)	Quality of Life - AD: score 0-52; higher scores reflect greater life satisfaction	measured at 1, 3, 6, 9, & 12 months
Secondary	Blood amyloid-beta 42 and 40	20 mL blood sample collection	measured at 1, 3, 6, 9, & 12 months
Secondary	Blood phosphorylated tau 181	20 mL blood sample collection	measured at 1, 3, 6, 9, & 12 months
Secondary	Blood total tau, neurofilament light chain	20 mL blood sample collection	measured at 1, 3, 6, 9, & 12 months