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| ID | Type | Description | Link |
|---|---|---|---|
| P0048639 | Other Grant/Funding Number | The Hong Kong Polytechnic University |
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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:
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)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| 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 |
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| 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Theta burst stimulation | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Six Minutes Walking Test | The Six Minutes Walking Test is a standard assessment for mobility | Baseline, 3 months, and 6 months |
| Timed-Up-and-Go Test | The Timed-Up-and-Go Test is a standard assessment for mobility and gait |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| JINGYI WU, MSc | Contact | +85260730847 | 24144838r@connect.polyu.hk |
| Name | Affiliation | Role |
|---|---|---|
| Chun Liang HSU, PhD | The Hong Kong Polytechnic University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Hong Kong Polytechnic University, Department of Rehabilitation Sciences | Recruiting | Hong Kong | Hong Kong |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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| Aerobic exercise | Behavioral | 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. |
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| Baseline, 3 months, and 6 months |
| Task Switch Test | The Task Switch Test is a standard assessment for executive function | Baseline, 3 months, and 6 months |
| Digit Span Test | The Digit Span Test is a standard assessment for executive function | Baseline, 3 months, and 6 months |
| Digit Symbol Substitution Test | The Digit Symbol Substitution Test is a standard assessment for executive function | Baseline, 3 months, and 6 months |
| Stroop Test | The Stroop Test is a standard assessment for executive function | Baseline, 3 months, and 6 months |
| Trail Making Test | The Trail Making Test is a standard assessment for executive function | Baseline, 3 months, and 6 months |
| Sit to stand | The Sit to stand is a standard assessment for mobility | Baseline, 3 months, and 6 months |
| 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. | Baseline, 3 months, and 6 months |
| 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. | Baseline, 3 months, and 6 months |
| Physical Activity Scale for the Elderly | Physical activity will be assessed by Physical Activity Scale for the Elderly | Baseline, 3 months, and 6 months |
| Geriatric Depression Scale | Depression will be measured by Geriatric Depression Scale | Baseline, 3 months, and 6 months |
| Fatigue Severity Scale | Physical fatigue will be measured by Fatigue Severity Scale | Baseline, 3 months, and 6 months |
| Functional Comorbidity Index | Total number of comorbid conditions will be assessed through the Functional Comorbidity Index | Baseline, 3 months, and 6 months |
| Functional Activities Questionnaire | The difficulties in activities of daily living will be assessed using the Functional Activities Questionnaire. | Baseline, 3 months, and 6 months |