NCT07497334

Brief 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. Understanding these effects will help us develop intervention models that benefit cognitively frail older adults. The main questions it aims to answer are:

  1. 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. 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?

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P25-P50 for not_applicable

Timeline
12mo left

Started Jan 2025

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress58%
Jan 2025Jun 2027

Study Start

First participant enrolled

January 5, 2025

Completed
1.2 years until next milestone

First Submitted

Initial submission to the registry

March 23, 2026

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 27, 2026

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2027

Last Updated

March 27, 2026

Status Verified

January 1, 2026

Enrollment Period

2.5 years

First QC Date

March 23, 2026

Last Update Submit

March 23, 2026

Conditions

Frailty at Older AdultsMild Cognitive Impairment

Keywords

cognitive frailtycTBSiTBSaerobic exercisefMRI

Outcome Measures

Primary Outcomes (3)

  • Montreal Cognitive Assessment

    General cognitive function will be measured by Montreal Cognitive Assessment

    Baseline, 3 months, and 6 months

  • Short Physical Performance Battery

    Mobility will be measured by Short Physical Performance Battery

    Baseline, 3 months, and 6 months

  • Pictorial Fit-Frail Scale

    The assessment of frailty in older adults will be conducted using the Pictorial Fit-Frail Scale.

    Baseline, 3 months, and 6 months

Secondary Outcomes (15)

  • Six Minutes Walking Test

    Baseline, 3 months, and 6 months

  • Timed-Up-and-Go Test

    Baseline, 3 months, and 6 months

  • Task Switch Test

    Baseline, 3 months, and 6 months

  • Digit Span Test

    Baseline, 3 months, and 6 months

  • Digit Symbol Substitution Test

    Baseline, 3 months, and 6 months

  • +10 more secondary outcomes

Study Arms (3)

cTBS+iTBS, in addition to aerobic exercise

EXPERIMENTAL

Participants will receive 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

Device: Theta burst stimulationBehavioral: Aerobic exercise

Sham cTBS + iTBS, in addition to aerobic exercise

ACTIVE COMPARATOR

Participants 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

Device: Theta burst stimulationBehavioral: Aerobic exercise

Sham cTBS + sham iTBS, in addition to aerobic exercise

SHAM COMPARATOR

Participants 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

Device: Theta burst stimulationBehavioral: Aerobic exercise

Interventions

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 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.

Sham cTBS + iTBS, in addition to aerobic exerciseSham cTBS + sham iTBS, in addition to aerobic exercisecTBS+iTBS, in addition to aerobic exercise
Aerobic exerciseBEHAVIORAL

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.

Sham cTBS + iTBS, in addition to aerobic exerciseSham cTBS + sham iTBS, in addition to aerobic exercisecTBS+iTBS, in addition to aerobic exercise

Eligibility Criteria

Age60 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • be between 60 and 90 years old;
  • scored \< 9/12 on the SPPB;
  • scored \>18/30 on the MoCA;
  • scored \>9/42 on the PFFS;
  • 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.

You may not qualify if:

  • have magnetic resonance imaging (MRI) 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Hong Kong Polytechnic University, Department of Rehabilitation Sciences

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Exercise

Condition Hierarchy (Ancestors)

Cognition DisordersNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Motor ActivityMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological Phenomena

Study Officials

  • Chun Liang HSU, PhD

    The Hong Kong Polytechnic University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

JINGYI WU, MSc

CONTACT

+8526073084724144838r@connect.polyu.hk

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 23, 2026

First Posted

March 27, 2026

Study Start

January 5, 2025

Primary Completion (Estimated)

June 30, 2027

Study Completion (Estimated)

June 30, 2027

Last Updated

March 27, 2026

Record last verified: 2026-01

Locations

HK(1)