A Novel Multi-Modal Approach to Promote Functional Outcomes in Cognitively Frail Older Adults (TMS MRI TBS)

The Hong Kong Polytechnic University

Status: Enrolling

Conditions: Mild Cognitive Impairment; Frailty at Older Adults

Treatments: Behavioral: Aerobic exercise; Device: Theta burst stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT07497334

P0048639 (Other Grant/Funding Number)

HSEARS20240614001

Details and patient eligibility

About

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?

Full 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)

Enrollment: 45 estimated patients

Sex: All

Ages: 60 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. be between 60 and 90 years old;
2. scored < 9/12 on the SPPB;
3. scored >18/30 on the MoCA;
4. scored >9/42 on the PFFS;
5. lived in the community;
6. be able to ambulate up to four meters with or without assistive devices;
7. be able to provide written informed consent on their own behalf;
8. can understand verbal and written Cantonese and/or English.

Exclusion criteria

1. have magnetic resonance imaging (MRI) contraindications;
2. have aerobic exercise contraindications;
3. have transcranial magnetic stimulation contraindications;
4. be diagnosed with neurodegenerative conditions (i.e., dementia, Parkinson's, Alzheimer's disease, Amyotrophic lateral sclerosis, and stroke);
5. live in a nursing home or other care facilities/institutions;
6. 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.
7. have a history indicative of carotid sinus sensitivity (i.e., falls due to loss of consciousness);
8. cancer and undergo radiation therapy.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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45 participants in 3 patient groups

cTBS+iTBS, in addition to aerobic exercise

Experimental group

Description:

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

Treatment:

Device: Theta burst stimulation

Behavioral: Aerobic exercise

Sham cTBS + iTBS, in addition to aerobic exercise

Active Comparator group

Description:

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

Treatment:

Device: Theta burst stimulation

Behavioral: Aerobic exercise

Sham cTBS + sham iTBS, in addition to aerobic exercise

Sham Comparator group

Description:

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

Treatment:

Device: Theta burst stimulation

Behavioral: Aerobic exercise