Clinical Efficacy of Intermittent Theta Burst Transcranial Magnetic Stimulation With Different Modes on Parkinson's Disease

NCT ID: NCT07176091

Last Updated: 2026-02-13

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-01
• Study Completion Date: 2027-06-01

Brief Summary

TMS regulates cortical excitability through electromagnetic induction, with low-frequency stimulation suppressing and high-frequency stimulation enhancing excitability. Building on theta-gamma coupling, iTBS induces broader improvements in functional brain connectivity within a shorter stimulation period, particularly by significantly reducing abnormal variability in the prefrontal and parietal regions, demonstrating superior neuromodulatory efficiency and network remodeling capacity. This study aims to compare the symptomatic effects of different iTBS protocols on Parkinson's disease, optimize stimulation parameters, and evaluate safety, while also analyzing the time-dependent trends of therapeutic efficacy through 1- and 3-month follow-ups.

Detailed Description

Transcranial magnetic stimulation, as a neuromodulatory strategy, has received increasing attention in the treatment of Parkinson's disease, demonstrating the ability to improve both motor and non-motor symptoms. Its mechanism is based on electromagnetic induction, using time-varying magnetic fields to modulate cortical neuronal activity. The effects of TMS are frequency-dependent: low-frequency stimulation (≤1 Hz) typically inhibits cortical excitability, resembling long-term depression, while high-frequency stimulation (≥10 Hz) enhances cortical excitability, analogous to long-term potentiation. Building on the mechanism of theta-gamma coupling, theta burst stimulation was developed by embedding high-frequency bursts within a theta rhythm, enabling efficient induction of LTP- and LTD-like effects. Among TBS protocols, intermittent TBS has been shown to exert clear modulatory effects on the motor cortex. Compared with 10 Hz repetitive TMS, iTBS induces broader improvements in functional connectivity across brain regions within a shorter stimulation period, particularly by significantly reducing abnormal variability in the prefrontal and parietal regions, indicating greater neuromodulatory efficiency and network remodeling capacity.

In this study, the iTBS protocol is applied based on the "Stanford Accelerated Intelligent Neuromodulation Therapy" (SAINT) approach. Patients are randomly assigned to one of three groups: a high-dose treatment group, a low-dose treatment group, or a sham stimulation group. Clinical scales are used to evaluate whether different modes of intermittent theta-burst transcranial magnetic stimulation improve motor and non-motor symptoms (particularly pain) in patients with Parkinson's disease. In addition, functional magnetic resonance imaging and electroencephalography are performed before and after treatment to explore the effects of different iTBS protocols on brain network activity and functional connectivity.

Conditions

Parkinsonism; Transcranial Magnetic Stimilation; Intermittent Theta Burst Stimulation; Primary Motor Cortex; Electroencephalography; Neuromodulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

High-dose iTBS treatment group

High-dose iTBS, 5 sessions per day for 5 consecutive days.

Group Type: EXPERIMENTAL

High-dose iTBS treatment group

Intervention Type: PROCEDURE

The stimulation intensity is 80% of the resting motor threshold (RMT), with an intra-burst frequency of 50 Hz and an inter-burst frequency of 5 Hz. Each train lasts 2 seconds, followed by an 8-second inter-train interval, delivering 1,800 pulses per session. The session is repeated after a 30-minute interval, with a total of 5 sessions per day (amounting to 9,000 pulses daily). Stimulation is administered for 5 consecutive days, resulting in a total of 45,000 pulses.

Low-dose iTBS treatment group

Conventional-dose iTBS, once daily for 5 consecutive days.

Group Type: EXPERIMENTAL

Low-dose iTBS treatment group

Intervention Type: PROCEDURE

The stimulation intensity is 80% of the resting motor threshold (RMT), with an intra-burst frequency of 50 Hz and an inter-burst frequency of 5 Hz. Each train lasts 2 seconds, followed by an 8-second inter-train interval, delivering 1,800 pulses per session. Stimulation is administered once daily (1,800 pulses per day) for 5 consecutive days, resulting in a total of 9,000 pulses.

Sham stimulation group

Administer sham stimulation

Group Type: SHAM_COMPARATOR

Sham stimulation group

Intervention Type: PROCEDURE

The intervention procedure is identical to that of active stimulation, with the sole difference being the use of a specific sham coil. This sham coil has the same appearance as the active coil but is specially modified to produce no magnetic field, generating only vibration and sound.

Interventions

High-dose iTBS treatment group

The stimulation intensity is 80% of the resting motor threshold (RMT), with an intra-burst frequency of 50 Hz and an inter-burst frequency of 5 Hz. Each train lasts 2 seconds, followed by an 8-second inter-train interval, delivering 1,800 pulses per session. The session is repeated after a 30-minute interval, with a total of 5 sessions per day (amounting to 9,000 pulses daily). Stimulation is administered for 5 consecutive days, resulting in a total of 45,000 pulses.

Intervention Type: PROCEDURE

Low-dose iTBS treatment group

The stimulation intensity is 80% of the resting motor threshold (RMT), with an intra-burst frequency of 50 Hz and an inter-burst frequency of 5 Hz. Each train lasts 2 seconds, followed by an 8-second inter-train interval, delivering 1,800 pulses per session. Stimulation is administered once daily (1,800 pulses per day) for 5 consecutive days, resulting in a total of 9,000 pulses.

Intervention Type: PROCEDURE

Sham stimulation group

The intervention procedure is identical to that of active stimulation, with the sole difference being the use of a specific sham coil. This sham coil has the same appearance as the active coil but is specially modified to produce no magnetic field, generating only vibration and sound.

Intervention Type: PROCEDURE

Other Intervention Names

The group treated with tDCS; The group treated with rTMS

Eligibility Criteria

Inclusion Criteria

• Aged 40-80 years; ② Diagnosis of idiopathic Parkinson's disease meeting the MDS Clinical Diagnostic Criteria for Parkinson's disease (2015 edition), with a disease duration of at least 3 years and Hoehn & Yahr stage < 4;

• Stable use of anti-parkinsonian medication for 2 weeks prior to the study and throughout the entire study period, with no dosage adjustments; ④ Concurrently meeting the diagnostic criteria for Parkinson's disease-related pain, with a frequency of at least 3 times per week and duration of at least 3 months; Numerical Rating Scale (NRS) score ≥ 3; ⑤ Passing the TMS Safety Screening Questionnaire (TSSQ);

Exclusion Criteria

• Patients with other diseases that may affect peripheral nerve sensation, including but not limited to diabetes, herpes infection, stroke, or spinal cord disorders;

• Patients with comorbid severe depression or psychiatric disorders;

• Presence of severe cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score ≤ 9;

• Patients with concurrent intracranial organic lesions or a history of traumatic brain injury; ⑤ Patients with severe organic diseases involving the heart, liver, kidneys, or other vital organs; ⑥ Patients unable to undergo cranial MRI examination or TMS treatment due to claustrophobia, presence of implanted devices such as pacemakers, history of epilepsy, or other contraindications.

• Providing written informed consent.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Cheng-Jie Mao

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Countries

China

References

Liu S, Yang S, Wang C, Li J, Wang L. Effects of two types of repetitive transcranial magnetic stimulation on brain network in Parkinson's disease. NPJ Parkinsons Dis. 2025 Jul 1;11(1):191. doi: 10.1038/s41531-025-01054-4.

Reference Type: BACKGROUND

PMID: 40593930 (View on PubMed)

Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.

Reference Type: BACKGROUND

PMID: 15664172 (View on PubMed)

Galanis C, Hananeia N, Lenz M, Vasheghani Farahani M, Jedlicka P, Vlachos A. Repetitive magnetic stimulation induces plasticity of excitatory synapses through cooperative pre- and postsynaptic activity. Brain Stimul. 2025 Sep-Oct;18(5):1641-1650. doi: 10.1016/j.brs.2025.08.019. Epub 2025 Aug 23.

Reference Type: BACKGROUND

PMID: 40850522 (View on PubMed)

Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA. 2020 Feb 11;323(6):548-560. doi: 10.1001/jama.2019.22360.

Reference Type: BACKGROUND

PMID: 32044947 (View on PubMed)

Other Identifiers

LK2025027

Identifier Type: -

Identifier Source: org_study_id