The Effect of Intermittent Theta Burst Stimulation on Brain Characteristics, Pain Intensity, and Cognitive Functions in Older People with Chronic Musculoskeletal Pain.

The Effect of Intermittent Theta Burst Stimulation on Brain Characteristics, Pain Intensity, and Cognitive Functions in Older People with Chronic Musculoskeletal Pain: a Double-blinded, Randomized, Sham-controlled, Mixed-methods, Pilot Trial with a Six-month Post-treatment Follow-up.

The goal of this clinical trial is to explore the effects of accelerated intermittent Theta Burst Stimulation (iTBS) on pain relief and cognitive function in older adults with chronic musculoskeletal pain. It will also utilize magnetic resonance imaging to illustrate the neurophysiological mechanisms underlying the role of iTBS in improving various outcome indicators in this population.

The main questions it aims to answer are:

1. Is left dorsolateral prefrontal cortex stimulation using accelerated iTBS effective for older adults with chronic musculoskeletal pain?
2. What are the neurophysiological mechanisms underlying the role of iTBS in improving various outcome indicators in older adults with chronic musculoskeletal pain?

Participants will:

1. Receive 1,200 stimuli during a single-session iTBS, totaling 14 days.
2. Undergo MRI scanning before, immediately after treatment, cognitive and pain-related tests before, immediately after treatment, and during follow-up.

Study Overview

• Status: Recruiting
• Conditions: Chronic Musculoskeletal Pain; Chronic Knee Pain; Chronic Non-Specific Low Back Pain
• Intervention / Treatment: Device: ITBS

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fan Dr. Huang; Phone Number: +852 5303 7752; Email: fan2023.huang@connect.polyu.hk
• Study Contact Backup: Name: Yat Ching Miss Wong; Phone Number: +852 60799195; Email: yatching.wong@connect.polyu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • The Hong Kong Polytechnic University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• have normal cognitive function (Hong Kong Montreal Cognitive Assessment ≥ 26)
• be right-handed
• be able to speak Cantonese
• chronic nonspecific low back pain, or having both chronic nonspecific low back pain and chronic knee pain that has lasted for at least 3 months
• an average pain intensity of ≥ 5 out of 10 on an 11-point numerical rating scale in the last 7 days, where 0 means "no pain" and 10 means "worst pain imaginable"
• having pain at least half of the days in the past 4 weeks.
• have at least 6 years of formal education and know how to read and write Chinese
• agree to sign an informed consent and complete the experiment tests
• be able to communicate via email or text message, as several study measures will be collected electronically

Exclusion Criteria:

• inability to ambulate without assistance from another person (canes or walkers will be allowed);
• having specific causes of chronic nonspecific low back pain, or having both chronic nonspecific low back pain and chronic knee pain (e.g., spinal stenosis, lumbar disc herniation, spondylolisthesis, recent vertebral fracture, spinal infection);
• having other concurrent musculoskeletal conditions at other body parts (e.g., fibromyalgia, or neck pain)
• self-reported history of lumbar or lower extremity surgery
• self-reported history of neurological or psychiatric disorders (e.g., stroke, brain surgery, head trauma; schizophrenia, multiple personality disorder, dissociative identity disorder, stroke) or self-reported cancer history
• self-reported specific inflammatory disorder: rheumatoid arthritis, rheumatica, scleroderma, lupus, or polymyositis
• unexplained, unintended weight loss of 20 lbs or more in the past year
• cauda equina syndrome
• uncorrected visual deficit
• drug or alcohol addiction
• taken alcohol, opioids or benzodiazepines medicines 24 hours before the experiment
• claustrophobia
• contraindications for undergoing the magnetic resonance imaging (MRI) examination based on the MRI safety screening form of University Research Facility in Behavioral and Systems Neuroscience (UBSN) at The Hong Kong Polytechnic University (PolyU)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham	Device: ITBS; We will use a coil called Cool-6000 A/P to conduct real and sham control. This coil will be placed on the scalp of older adults. The iTBS protocol will begin with a 2-s burst train (totally 30 pulses), repeating every 10 s. Each burst train will consist of 10 triplet pulses with an inter-burst interval of 0.16 s, thus the triplets fire at a rate of 5 Hz. ITBS parameters will include three continuous pulses at 50 Hz repeated at 5 Hz (2s on, 8s off) for a total of 600 pulses. We will administer two rounds of iTBS per treatment day, with a 15-minute interval between the two sessions. In total, each participant will receive 1,200 stimuli during a single-session iTBS, totaling for 14 days. Each treatment session will last for about 30 minutes. Intermittent θ-burst stimulation intensity will be set at 70% of the resting motor threshold.
Experimental: Left DLPFC	Device: ITBS; We will use a coil called Cool-6000 A/P to conduct real and sham control. This coil will be placed on the scalp of older adults. The iTBS protocol will begin with a 2-s burst train (totally 30 pulses), repeating every 10 s. Each burst train will consist of 10 triplet pulses with an inter-burst interval of 0.16 s, thus the triplets fire at a rate of 5 Hz. ITBS parameters will include three continuous pulses at 50 Hz repeated at 5 Hz (2s on, 8s off) for a total of 600 pulses. We will administer two rounds of iTBS per treatment day, with a 15-minute interval between the two sessions. In total, each participant will receive 1,200 stimuli during a single-session iTBS, totaling for 14 days. Each treatment session will last for about 30 minutes. Intermittent θ-burst stimulation intensity will be set at 70% of the resting motor threshold.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The recruitment rate, retention rate (completion rate), non-completion reasons, drop-out rate	The recruitment rate, retention rate (completion rate), non-completion reasons, drop-out rate will be evaluated as our primary outcomes, because of the feasibility of the study.	Immediately after the intervention
ITBS acceptability questionnaire	ITBS acceptability questionnaire has ten items of positive acceptability, ranged from 10 to 50, and it also has five items of negative acceptability, ranged from 5 to 25. The iTBS acceptability questionnaire has a total score ranging from 15 to 75.	Immediately after the intervention
Pain intensity assessment	The 11-point numerical rating scale, ranged from 0 to 10, higher scores indicate higher pain intensity.	Baseline, immediately after the intervention, five-month follow-up at one-month,three-month,six-month follow-up timepoints.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression, anxiety, and stress test	The Chinese version of the short Depression Anxiety Stress Scales, scores ranged from 0 to 13, higher scores for each domain (depression, anxiety, and stress) indicate more respective problems.	Baseline
Pain drawing test	The body map scoring system indicates the location of participants' painful site	Baseline
Cognitive function screening	Hong Kong Montreal Cognitive Assessment. It is a cognitive screening tool specifically adapted for Chinese older adults in Hong Kong. It is designed to detect mild cognitive impairment and dementia. A score < 26 suggests participant has mild cognitive impairment.	Baseline
Working memory test inside magnetic resonance imaging scanning	The digit 2-back task, more response accuracy of digits indicates better working memory	Baseline, immediately after the intervention
Cognitive flexibility test inside magnetic resonance imaging scanning	The More Odd Shifting task, It requires participants to switch between different mental sets or rules, such as identifying odd numbers or shifting between different categories. Better response accuracy indicates better cognitive flexibility	Baseline, immediately after the intervention.
Cognitive inhibition test inside magnetic resonance imaging scanning	Color-Word Matching Stroop Task, more correct matching indicate better ability to inhibit cognitive interference	Baseline, immediately after the intervention.
Disability evaluation	The Hong Kong Chinese Version of the Roland-Morris Disability Questionnaire has 24 items. Scores ranged from 0 to 24, higher scores indicate worse disability.	Baseline, immediately after the intervention, five-month follow-up at one-month,three-month,six-month follow-up timepoints.
Pain catastrophizing assessment	The Chinese version of Pain Catastrophizing Score. The scores ranged from 0 to 13, higher scores indicate more pain catatrophizing thought.	Baseline, immediately after the intervention, five-month follow-up at one-month,three-month,six-month follow-up timepoints.
Frailty status assessment	Fatigue, Resistance, Ambulation, Illness, and Loss, the presence of 3 of 5 item characteristics indicate the presence of frailty, scores ranged from 0 to 5. Lower scores mean more frailty.	Baseline, immediately after the intervention, one-month follow-up timepoint.
Physical activity assessment	Physical Activity Scale for the Elderly; it has 3 domains (leisure, household, and occupation activities) to measure physical activity levels of adults aged 65 or above. higher scores indicate more active.	Baseline, immediately after the intervention, one-month follow-up timepoint.
Sleep quality assessment	Pittsburgh Sleep Quality Index. It has 7 domains to measure sleep quality , sleep latency, sleep duration, habital sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. Scores ranged from 0 to 21, higher scores indicate poorer sleep quality.	Baseline, immediately after the intervention, one-month follow-up timepoint.
Perseveration and abstract reasoning test outside magnetic resonance imaging scanning	The Modified Wisconsin Card Sorting Test, more correct matching of cards indicate better perseveration and abstract reasoning.	Baseline, immediately after the intervention, one-month follow-up timepoint.
Working memory Test outside magnetic resonance imaging scanning	The Verbal Digits Forward and Backward Test, more correct recall of digits indicate better working memory and executive function	Baseline, immediately after the intervention, one-month follow-up timepoint.
Cognitive flexibility test outside magnetic resonance imaging scanning	The Trail Making Tests, a neuropsychological test of visual attention and task switching, completing the trail correctly within a shorter period of time means better cognitive flexibility	Baseline, immediately after the intervention, one-month follow-up timepoint.
Inhibition test outside magnetic resonance imaging scanning	Go/NoGo task, more response accuracy indicates better control of inhibition.	Baseline, immediately after the intervention, one-month follow-up timepoint.

Collaborators and Investigators

• Sponsor: The Hong Kong Polytechnic University
• Investigators: Principal Investigator: Arnold Dr WONG, The Hong Kong Polytechnic University

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: November 25, 2024
• First Posted (Actual): November 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: chronic musculoskeletal pain; rTMS; Sham; iTBS; DLPFC; Chronic non-specific low back pain; Chronic knee pain
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Back Pain; Pain; Musculoskeletal Pain; Low Back Pain
• Other Study ID Numbers: HSEARS20240411013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes