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Mild Cognitive ImpairmentSMARTNCT05877196

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

A study testing Moderate Intensity Continuous Training (MICT), Chair-based Stretch and High-Intensity Interval Training (HIIT) in people with Mild Cognitive Impairment and Alzheimer Disease, run by Arizona State University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 65 years and olderHealthy volunteers can take part
What is being tested?
Moderate Intensity Continuous Training (MICT), Chair-based Stretch and High-Intensity Interval Training (HIIT)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
216 participants
Where
1 siteUnited States
Study dates
22 Jun 2023to 30 Jun 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

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
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Kristi Spieleder, MS contact

480-884-2765

kspieled@asu.edu

United States1 site, 1 recruiting

  • Arizona State University

    Phoenix, Arizona, 85004

    Kristi Spieleder, MS, 480-884-2765, kspieled@asu.edu

    Fang Yu, PhD

    Recruiting

Other trials in United States

About this study

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)

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.

Read the 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.

Being tested
Moderate Intensity Continuous Training (MICT), Chair-based Stretch, High-Intensity Interval Training (HIIT), Combined Aerobic Resistance Exercise (CARE)
Medical subject headings
Cognitive Dysfunction, Alzheimer Disease, Memory Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Moderate Intensity Continuous Training (MICT)Behavioural

    Also called Continuous Training, Aerobic exercise, Cardio

    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 StretchBehavioural

    Also called Stretch, Range of motion, flexibility

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

  • High-Intensity Interval Training (HIIT)Behavioural

    Also called HIIT, Vigorous training, Hard exercise

    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)Behavioural

    Also called Strength and Cardio Training, CARE, Combination training, Exercise training

    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.

Study groups in NCT05877196
Study groupRoleWhat they receive
Moderate Intensity Continuous Training (MICT)ExperimentalCycling on recumbent stationary cycle at moderate intensity for 30-50 minutes, 3 times per week for 3-6 months
Receives: Behavioral: Moderate Intensity Continuous Training (MICT)
Chair-based StretchSham comparatorStretching at low intensity for 30-50 minutes, 3 times per week for 6 months
Receives: Behavioral: Chair-based Stretch
High-Intensity Interval Training (HIIT)Active comparatorMICT 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.
Receives: Behavioral: High-Intensity Interval Training (HIIT)
Combined Aerobic Resistance Exercise (CARE)Active comparatorMICT 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.
Receives: Behavioral: Combined Aerobic Resistance Exercise (CARE)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Peak oxygen consumption

    VO2peak will be assessed from the symptom-limited peak cycle-ergometer test

    Measured: measured at 0 and 6 months

  2. White Matter Hyperintensity volume

    WMH will be assessed from MRI.

    Measured: measured at 0 and 6 months

Secondary outcomes (8)

  1. Memory

    Wechsler Memory Scale - Revised; Logical Memory; score 0-50; higher scores indicate less impairment

    Measured: measured at 0, 6, and 12 months

  2. Physical function

    Short Physical Performance Battery: score 0-12; lower scores indicate poorer physical function

    Measured: measured at 0, 3, 6, 9, & 12 months

  3. Behavioral and psychiatric symptoms of dementia (BPSD)

    Neuropsychiatric Inventory Questionnaire; symptoms present, if yes, then severity and caregiver distress are reported.

    Measured: measured at 1, 3, 6, 9, & 12 months

  4. Caregiver burden

    4-item Zarit Burden Interview: score 0-16; higher scores reflect greater burden

    Measured: measured at 1, 3, 6, 9, & 12 months

  5. Quality of Life (QoL)

    Quality of Life - AD: score 0-52; higher scores reflect greater life satisfaction

    Measured: measured at 1, 3, 6, 9, & 12 months

  6. Blood amyloid-beta 42 and 40

    20 mL blood sample collection

    Measured: measured at 1, 3, 6, 9, & 12 months

  7. Blood phosphorylated tau 181

    20 mL blood sample collection

    Measured: measured at 1, 3, 6, 9, & 12 months

  8. Blood total tau, neurofilament light chain

    20 mL blood sample collection

    Measured: measured at 1, 3, 6, 9, & 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 May 2023
  2. Study start22 Jun 2023
  3. Primary completion1 Apr 2027 (estimated)
  4. Study completion30 Jun 2028 (estimated)

Resources

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
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Sequential, Multiple Assignment, Randomized Trial
Masking
Double blind
Who is masked
Investigator, Outcomes assessor
Enrolment
216 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05877196
Sponsor's protocol ID
STUDY00017678
Acronym
SMART
Status last verified
May 2026
First submitted
3 Apr 2023
Last updated
5 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • Almirall D, Nahum-Shani I, Sherwood NE, Murphy SA. Introduction to SMART designs for the development of adaptive interventions: with application to weight loss research. Transl Behav Med. 2014 Sep;4(3):260-74. doi: 10.1007/s13142-014-0265-0.

    PubMed 25264466

  • Salisbury D, Mathiason MA, Yu F. Exercise Dose and Aerobic Fitness Response in Alzheimer's Dementia: Findings from the FIT-AD Trial. Int J Sports Med. 2022 Sep;43(10):850-858. doi: 10.1055/a-1639-2307. Epub 2021 Sep 7.

    PubMed 34492709

  • Pandey A, Swift DL, McGuire DK, Ayers CR, Neeland IJ, Blair SN, Johannsen N, Earnest CP, Berry JD, Church TS. Metabolic Effects of Exercise Training Among Fitness-Nonresponsive Patients With Type 2 Diabetes: The HART-D Study. Diabetes Care. 2015 Aug;38(8):1494-501. doi: 10.2337/dc14-2378. Epub 2015 Jun 17.

    PubMed 26084342

  • Huang G, Wang R, Chen P, Huang SC, Donnelly JE, Mehlferber JP. Dose-response relationship of cardiorespiratory fitness adaptation to controlled endurance training in sedentary older adults. Eur J Prev Cardiol. 2016 Mar;23(5):518-29. doi: 10.1177/2047487315582322. Epub 2015 Apr 21.

    PubMed 25901000

  • Salisbury D, Yu F. Establishing Reference Cardiorespiratory Fitness Parameters in Alzheimer's Disease. Sports Med Int Open. 2020 Jan 30;4(1):E1-E7. doi: 10.1055/a-1089-4957. eCollection 2020 Jan.

    PubMed 32010759

  • Gomes-Neto M, Duraes AR, Conceicao LSR, Roever L, Silva CM, Alves IGN, Ellingsen O, Carvalho VO. Effect of combined aerobic and resistance training on peak oxygen consumption, muscle strength and health-related quality of life in patients with heart failure with reduced left ventricular ejection fraction: a systematic review and meta-analysis. Int J Cardiol. 2019 Oct 15;293:165-175. doi: 10.1016/j.ijcard.2019.02.050. Epub 2019 Jun 24.

    PubMed 31345646

  • Lee J, Lee R, Stone AJ. Combined Aerobic and Resistance Training for Peak Oxygen Uptake, Muscle Strength, and Hypertrophy After Coronary Artery Disease: a Systematic Review and Meta-Analysis. J Cardiovasc Transl Res. 2020 Aug;13(4):601-611. doi: 10.1007/s12265-019-09922-0. Epub 2019 Oct 27.

    PubMed 31656988

  • Lee J, Stone AJ. Combined Aerobic and Resistance Training for Cardiorespiratory Fitness, Muscle Strength, and Walking Capacity after Stroke: A Systematic Review and Meta-Analysis. J Stroke Cerebrovasc Dis. 2020 Jan;29(1):104498. doi: 10.1016/j.jstrokecerebrovasdis.2019.104498. Epub 2019 Nov 13.

    PubMed 31732460

  • Hautala AJ, Makikallio TH, Kiviniemi A, Laukkanen RT, Nissila S, Huikuri HV, Tulppo MP. Cardiovascular autonomic function correlates with the response to aerobic training in healthy sedentary subjects. Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1747-52. doi: 10.1152/ajpheart.00202.2003. Epub 2003 Jun 19.

    PubMed 12816748

  • Burns JM, Johnson DK, Watts A, Swerdlow RH, Brooks WM. Reduced lean mass in early Alzheimer disease and its association with brain atrophy. Arch Neurol. 2010 Apr;67(4):428-33. doi: 10.1001/archneurol.2010.38.

    PubMed 20385908

  • Sugimoto T, Ono R, Murata S, Saji N, Matsui Y, Niida S, Toba K, Sakurai T. Prevalence and associated factors of sarcopenia in elderly subjects with amnestic mild cognitive impairment or Alzheimer disease. Curr Alzheimer Res. 2016;13(6):718-26. doi: 10.2174/1567205013666160211124828.

    PubMed 26863996

  • Karlsen T, Aamot IL, Haykowsky M, Rognmo O. High Intensity Interval Training for Maximizing Health Outcomes. Prog Cardiovasc Dis. 2017 Jun-Jul;60(1):67-77. doi: 10.1016/j.pcad.2017.03.006. Epub 2017 Apr 3.

    PubMed 28385556

  • Levinger I, Shaw CS, Stepto NK, Cassar S, McAinch AJ, Cheetham C, Maiorana AJ. What Doesn't Kill You Makes You Fitter: A Systematic Review of High-Intensity Interval Exercise for Patients with Cardiovascular and Metabolic Diseases. Clin Med Insights Cardiol. 2015 Jun 25;9:53-63. doi: 10.4137/CMC.S26230. eCollection 2015.

    PubMed 26157337

  • Bossers WJ, van der Woude LH, Boersma F, Hortobagyi T, Scherder EJ, van Heuvelen MJ. A 9-Week Aerobic and Strength Training Program Improves Cognitive and Motor Function in Patients with Dementia: A Randomized, Controlled Trial. Am J Geriatr Psychiatry. 2015 Nov;23(11):1106-16. doi: 10.1016/j.jagp.2014.12.191. Epub 2015 Jan 3.

    PubMed 25648055

  • Yu F, Vock DM, Zhang L, Salisbury D, Nelson NW, Chow LS, Smith G, Barclay TR, Dysken M, Wyman JF. Cognitive Effects of Aerobic Exercise in Alzheimer's Disease: A Pilot Randomized Controlled Trial. J Alzheimers Dis. 2021;80(1):233-244. doi: 10.3233/JAD-201100.

    PubMed 33523004

Questions about this trial

What is this clinical trial studying?

A study testing Moderate Intensity Continuous Training (MICT), Chair-based Stretch and High-Intensity Interval Training (HIIT) in people with Mild Cognitive Impairment and Alzheimer Disease, run by Arizona State University at 1 site 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 13 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kristi Spieleder, MS (480-884-2765, kspieled@asu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak oxygen consumption (time frame: measured at 0 and 6 months). The study lists 2 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 NCT05877196, which also lists 53 linked publications.

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 5 May 2026.

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