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Frailty at Older AdultsTMS MRI TBSNCT07497334

A Novel Multi-Modal Approach to Promote Functional Outcomes in Cognitively Frail Older Adults

A study testing Theta burst stimulation and Aerobic exercise in people with Frailty at Older Adults and Mild Cognitive Impairment, run by The Hong Kong Polytechnic University at 1 site in Hong Kong.

Recruiting

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

Sites and contacts
Official record
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Trial summary

The goal of this clinical trial is to explore the effects of intermittent theta burst stimulation (iTBS) primed with theta burst stimulation (cTBS), on top of aerobic exercise, on cognitive function, mobility, and brain activity in older adults with cognitive frailty. Read more about this study

Who is it for?
Ages 60 to 90 years
What is being tested?
Theta burst stimulation and Aerobic exercise
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
45 participants
Where
1 siteHong Kong
Study dates
5 Jan 2025to 30 Jun 2027
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 60 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • be between 60 and 90 years old;
  • scored < 9/12 on the Short Physical Performance Battery;
  • scored >18/30 on the Montreal Cognitive Assessment;
  • scored >9/42 on the Pictorial Fit-Frail Scale;
  • lived in the community;
  • be able to ambulate up to four meters with or without assistive devices;
  • be able to provide written informed consent on their own behalf;
  • can understand verbal and written Cantonese and/or English.

Who cannot join

  • have magnetic resonance imaging contraindications;
  • have aerobic exercise contraindications;
  • have transcranial magnetic stimulation contraindications;
  • be diagnosed with neurodegenerative conditions (i.e., dementia, Parkinson's, Alzheimer's disease, Amyotrophic lateral sclerosis, and stroke);
  • live in a nursing home or other care facilities/institutions;
  • bed taking fixed dose of medication or had been taking medications known to potentially affect cognitive and physical function (e.g., psychotropic medications), as identified through a review of their medication lists recorded in the health software. Medications were categorized by properties (e.g., antipsychotics, antidepressants, etc.) to inform eligibility decisions.
  • have a history indicative of carotid sinus sensitivity (i.e., falls due to loss of consciousness);
  • cancer and undergo radiation therapy.

Trial locations and contacts

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

Hong Kong1 site, 1 recruiting
  • The Hong Kong Polytechnic University, Department of Rehabilitation Sciences

    Hong Kong

    Chun Liang HSU, PhD, 852-27666755, chun-liang.hsu@polyu.edu.hk

    Recruiting

Other trials in Hong Kong

About this study

The goal of this clinical trial is to explore the effects of intermittent theta burst stimulation (iTBS) primed with theta burst stimulation (cTBS), on top of aerobic exercise, on cognitive function, mobility, and brain activity in older adults with cognitive frailty. Understanding these effects will help us develop intervention models that benefit cognitively frail older adults. The main questions it aims to answer are:

  1. Does the combination of iTBS primed with cTBS and aerobic exercise lead to greater improvements in cognition and mobility in older adults with cognitive frailty compared to non-priming iTBS and sham stimulation?
  2. What are the neural mechanisms responsible for the improvements in cognition and mobility associated with the combination of iTBS primed with cTBS and aerobic exercise in older adults with cognitive frailty?
Read the detailed description

Objectives: To compare the effects of intermittent theta burst stimulation (iTBS) primed with continuous theta burst stimulation (cTBS), nonpriming iTBS, and sham stimulation on top of aerobic exercise in terms of improving cognitive function, mobility, brain structure, and brain function in older adults with cognitive frailty.

Hypothesis to be tested: We hypothesize that iTBS primed with cTBS can maximize the induction of therapeutically beneficial metaplasticity, and that this will be reflected in improved brain structure and brain function, thereby enabling superior cognitive function and mobility improvement in older adults with cognitive frailty.

Design and subjects: A randomized controlled trial involving 60 older adults with cognitive frailty.

Study instruments: Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI).

Interventions: Participants will be randomly allocated to receive a 39-session intervention with different TBS protocols (i.e., cTBS+iTBS, sham cTBS+iTBS, and sham cTBS+sham iTBS), delivered 3 times per week for 3 months. All participants will receive 60 minutes of aerobic exercise after each stimulation session for 6 months.

Main outcome measures: comprehensive neuropsychological battery covering major executive function (i.e., selective attention/response inhibition, psychomotor speed, set shifting), working memory, and verbal fluency; (2) mobility function evaluated via SPPB, Timed-Up-and-GO (TUG) test, functional gait analysis (i.e., gait speed, gait variability).

Secondary outcomes: underlying neural mechanisms of intervention-induced benefits will be assessed via functional and structural magnetic resonance imaging.

Data analysis: Analysis of variance (ANOVA)

Being tested
Theta burst stimulation, Aerobic exercise
Keywords
cognitive frailty, cTBS, iTBS, aerobic exercise, fMRI
Medical subject headings
Cognitive Dysfunction

What participants receive

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

  • Theta burst stimulationDevice

    Theta burst stimulation (TBS) will be administered using a figure-of-eight shaped cooling coil (Cool-B65 A/P), which generates auditory "clicks" for sham stimulation that are similar to those produced by active repetitive transcranial magnetic stimulation (rTMS). The placement of the coil will be guided by a navigation system (LOCALITE® TMS Navigator, Germany) using each participant's baseline T1-weighted Magnetic Resonance Imaging (MRI) scans.

    TBS is a powerful form of rTMS. Standard 600-pulse intermittent theta burst stimulation (iTBS) can enhance corticomotor excitability, whereas standard 600-pulse continuous theta burst stimulation (cTBS) can suppress it.

  • Aerobic exerciseBehavioural

    The aerobic exercise sessions will include a 10-minute warm-up, followed by 40 minutes of brisk walking and/or stationary exercises without weights, and will conclude with a 10-minute cooldown. The intensity of the aerobic exercise will be monitored using heart rate, starting at 40% of the age-specific heart rate reserve (HRR), which is calculated using the formula: 207 - (0.7 x age). Over the initial 12 weeks, the intensity will be gradually increased until the HRR reaches 65%, and this level will be maintained until the end of the trial.

Study groups in NCT07497334
Study groupRoleWhat they receive
cTBS+iTBS, in addition to aerobic exerciseExperimentalParticipants will receive 600-pulse continuous theta burst stimulation (cTBS) at the intensity of 80% resting motor threshold (RMT) as the priming, followed by 600-pulse intermittent theta burst stimulation (iTBS) at the intensity of 80% RMT (i.e., priming iTBS). The stimulation will be delivered 3 sessions per week, lasting for 3 months. Participants will receive a 60-minute aerobic exercise after each stimulation session, lasting for 6 months
Receives: Device: Theta burst stimulation; Behavioral: Aerobic exercise
Sham cTBS + iTBS, in addition to aerobic exerciseActive comparatorParticipants will receive sham 600-pulse cTBS at the intensity of 80% RMT as the priming, followed by 600-pulse iTBS at the intensity of 80% RMT (i.e., priming iTBS). The stimulation will be delivered 3 sessions per week, lasting for 3 months. Participants will receive a 60-minute aerobic exercise after each stimulation session, lasting for 6 months
Receives: Device: Theta burst stimulation; Behavioral: Aerobic exercise
Sham cTBS + sham iTBS, in addition to aerobic exerciseSham comparatorParticipants will receive sham 600-pulse cTBS at the intensity of 80% RMT as the priming, followed by sham 600-pulse iTBS at the intensity of 80% RMT (i.e., priming iTBS). The stimulation will be delivered 3 sessions per week, lasting for 3 months. Participants will receive a 60-minute aerobic exercise after each stimulation session, lasting for 6 months
Receives: Device: Theta burst stimulation; Behavioral: Aerobic exercise

What is being measured

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

  1. Montreal Cognitive Assessment

    General cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA). The total MoCA score ranges from 0 to 30, with higher scores indicating better cognitive performance

    Measured: Baseline, 3 months, and 6 months

  2. Short Physical Performance Battery

    Mobility will be assessed using the Short Physical Performance Battery (SPPB). The SPPB evaluates balance, gait speed, and chair stand performance, with total scores ranging from 0 to 12. Higher scores indicate better mobility

    Measured: Baseline, 3 months, and 6 months

  3. Pictorial Fit-Frail Scale

    Frailty in older adults will be assessed using the Pictorial Fit-Frail Scale (PFFS). The PFFS evaluates 14 health domains, with total scores ranging from 0 to 43. Higher scores indicate a greater severity of frailty.

    Measured: Baseline, 3 months, and 6 months

Secondary outcomes (15)
  1. Six Minutes Walking Test

    The Six-Minute Walk Test (6MWT) is a practical, self-paced clinical test that measures the total distance an individual can walk on a flat, hard surface in six minutes. A longer distance walked reflects a higher level of functional mobility.

    Measured: Baseline, 3 months, and 6 months

  2. Timed-Up-and-Go Test

    The Timed Up and Go (TUG) test is a standardized assessment used to evaluate mobility and gait. A longer completion time reflects poorer physical mobility.

    Measured: Baseline, 3 months, and 6 months

  3. Task Switch Test

    The Task Switching Test is a standardized assessment used to evaluate executive function. A higher accuracy rate and a shorter reaction time reflect superior executive performance

    Measured: Baseline, 3 months, and 6 months

  4. Digit Span Test

    The Digit Span Test is a standardized neuropsychological assessment used to evaluate attention and working memory. The test comprises two components: Digits Forward and Digits Backward. A higher cumulative score reflects better overall performance. Additionally, a smaller discrepancy score (calculated as the forward span minus the backward span) represents superior cognitive manipulation and updating ability.

    Measured: Baseline, 3 months, and 6 months

  5. Digit Symbol Substitution Test

    The Digit Symbol Substitution Test (DSST) is a standardized neuropsychological instrument used to evaluate cognitive processing speed and executive function. The total score is determined by the number of correctly completed items within a specified time limit, with higher scores reflecting superior cognitive performance.

    Measured: Baseline, 3 months, and 6 months

  6. Stroop Test

    The Stroop Test is a standardized neuropsychological assessment used to evaluate executive function, particularly inhibitory control. The completion time for each condition is recorded as the score, with shorter completion times reflecting superior executive performance.

    Measured: Baseline, 3 months, and 6 months

  7. Trail Making Test

    The Trail Making Test will comprise Part A and Part B. In Part A, participants are instructed to connect numbers in sequential order (e.g., drawing a line from 1 to 2, 2 to 3, 3 to 4, etc.) while being timed. In Part B, participants are instructed to connect, in order, 25 encircled numbers and letters alternately (e.g., 1-A-2-B-3-C) while being timed. A longer time represents worse executive function.

    Measured: Baseline, 3 months, and 6 months

  8. 30-second sit to stand

    Functional mobility and lower-limb functional strength will be measured via the 30-Second Chair Stand Test (30CST). Participants stand up and sit down as rapidly and safely as possible for 30 seconds, where a higher repetition score indicates greater functional mobility.

    Measured: Baseline, 3 months, and 6 months

  9. cortical and subcortical volume

    Cortical and subcortical volume will be examined in all participants using MRI. Participants will undergo structural MRI on the 3T Siemens scanner at the University Research Facility in Behavioral and Systems Neuroscience. Participants will complete T1 and T2 high resolution anatomical scans.

    Measured: Baseline, 3 months, and 6 months

  10. Resting State-Functional Connectivity-Functional MRI

    Participants will be instructed to rest with eyes open for approximately 12 minutes. This will allow the investigators to examine activation in the resting state network.

    Measured: Baseline, 3 months, and 6 months

  11. Physical Activity Scale for the Elderly

    Physical activity will be assessed by Physical Activity Scale for the Elderly (PASE), where a higher score indicates a higher level of physical activity.

    Measured: Baseline, 3 months, and 6 months

  12. Geriatric Depression Scale

    Depression will be measured by Geriatric Depression Scale (GDS), where a higher score indicates a higher level of depressive symptoms

    Measured: Baseline, 3 months, and 6 months

  13. Fatigue Severity Scale

    Physical fatigue will be measured by Fatigue Severity Scale (FSS), where a higher score indicates more severe fatigue

    Measured: Baseline, 3 months, and 6 months

  14. Functional Comorbidity Index

    Total number of comorbid conditions will be assessed through the Functional Comorbidity Index (FCI), where a higher score indicates a greater comorbidity burden.

    Measured: Baseline, 3 months, and 6 months

  15. Functional Activities Questionnaire

    The difficulties in activities of daily living will be assessed using the Functional Activities Questionnaire (FAQ), with higher scores reflecting severe difficulty in performing daily tasks.

    Measured: Baseline, 3 months, and 6 months

Timeline

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

  1. First posted27 Mar 2026
  2. Study start5 Jan 2025
  3. Primary completion30 Jun 2027 (estimated)
  4. Study completion30 Jun 2027 (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
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07497334
Sponsor's protocol ID
HSEARS20240614001
Other IDs
P0048639
Acronym
TMS MRI TBS
Status last verified
Sep 2026
First submitted
23 Mar 2026
Last updated
30 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A study testing Theta burst stimulation and Aerobic exercise in people with Frailty at Older Adults and Mild Cognitive Impairment, run by The Hong Kong Polytechnic University at 1 site in Hong Kong.

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 8 inclusion and 8 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 30 Sep 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 Hong Kong. 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 JINGYI WU, MSc (+85260730847, 24144838r@connect.polyu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Montreal Cognitive Assessment (time frame: Baseline, 3 months, and 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 30 Sep 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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