TIS for Brain Network Modulation and Clinical Efficacy in Parkinson's Disease

N/ANot Yet RecruitingNCT07480317

Jiangsu Province Nanjing Brain Hospital75 enrolled

Overview

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction. While deep brain stimulation (DBS) is effective, its invasive nature limits its application in early-stage patients. Temporal interference stimulation (TIS) is a novel non-invasive technique that can target deep brain structures like the globus pallidus internus (GPi) by using high-frequency electric fields. This study aims to evaluate the clinical value and underlying mechanisms of TIS in PD patients. The research is divided into two phases: Phase A investigates the immediate regulatory effects of 130 Hz and 40 Hz TIS on brain networks using concurrent fMRI-TIS. Phase B is a randomized, double-blind, sham-controlled trial to assess the long-term efficacy and safety of a 2-week TIS intervention on both motor and non-motor symptoms. The results will help clarify how TIS modulates deep brain networks and its potential as a non-invasive therapy for PD.

This study employs a two-phase design to systematically investigate the effects of Temporal Interference Stimulation (TIS) on Parkinson's Disease (PD). Phase A: Acute fMRI Mechanism Study (n=15) In this crossover study, participants will undergo concurrent fMRI-TIS sessions. Two frequency envelopes will be tested: 130 Hz (to mimic DBS inhibitory effects) and 40 Hz (for gamma entrainment). The fMRI protocol follows an 8-20-8 minute design: 8 minutes of baseline, 20 minutes of concurrent stimulation, and 8 minutes of post-stimulation scan . Individualized electric field modeling based on high-resolution 3D-T1 MRI will be used to target the right GPi. Acute motor changes will be assessed using the MDS-UPDRS-III scale. Phase B: Long-term Efficacy RCT (n=60) Participants will be randomly assigned to one of three parallel groups: 130 Hz TIS, 40 Hz TIS, or Sham stimulation. The intervention consists of 30-minute daily sessions for 2 weeks (10 sessions total). Active Groups: TIS targeting the right GPi with individualized electrode configurations. Sham Group: 20-second ramp-up and ramp-down to mimic skin sensation without continuous stimulation. Clinical assessments including motor function (MDS-UPDRS), cognition (MoCA), mood (HAMD/HAMA), and sleep (PDSS-2) will be conducted at baseline, after the 2-week intervention, and at a 1-month follow-up . Long-term neuroplasticity will also be evaluated using multi-modal MRI post-intervention.

Study Type

INTERVENTIONAL

Allocation

Interventions

Temporal Interference Stimulation (130 Hz)DEVICE

High-frequency sinewave currents (carrier frequency: 2000 Hz and 2130 Hz) are delivered via two pairs of scalp electrodes. The current intensity is 2-4 mA (individualized). In Phase B, stimulation lasts 30 minutes daily for 2 weeks (10 sessions).

Temporal Interference Stimulation (40 Hz)DEVICE

High-frequency sinewave currents (carrier frequency: 2000 Hz and 2040 Hz) are delivered via two pairs of scalp electrodes. Parameters are identical to the 130 Hz group except for the envelope frequency.

Sham Temporal Interference StimulationDEVICE

The device provides only a 20-second ramp-up and 20-second ramp-down of current to mimic the skin sensation of active stimulation, without continuous therapeutic stimulation.

Eligibility

Sex: ALLMin age: 45 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosed with Parkinson's Disease according to the Movement Disorder Society (MDS) clinical diagnostic criteria. * Hoehn \& Yahr Stage I-III (mild to moderate severity). * Aged 45 to 65 years. * Right-handed. Stable medication regimen for at least 1 hour before Phase A fMRI sessions and agreement to maintain a stable dosage during the 2-week Phase B intervention (unless clinically necessary). * Able to provide informed consent by the participant or a legal guardian. Exclusion Criteria: * MRI contraindications, such as implanted DBS electrodes, cardiac pacemakers, or other metal implants. * Significant cognitive impairment (MoCA score \< 24) or severe psychiatric symptoms. * History of epilepsy or structural brain lesions, including severe cerebral atrophy or cerebrovascular disease. * Severe head tremors that would interfere with MRI scanning quality.

Outcomes

Primary Outcomes

Change from Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) total score.

The MDS-UPDRS Part III is a clinician-rated scale used to assess the motor signs of Parkinson's disease. It includes 18 items (33 scores total), with each item ranging from 0 (normal) to 4 (severe). The total score ranges from 0 to 132, where higher scores represent greater motor impairment.

Time frame: Baseline, 2 weeks (immediately after the 10th intervention session), and 1 month (follow-up).

Secondary Outcomes

Changes in Brain Network Functional Connectivity and Amplitude of Low-frequency Fluctuations (ALFF).

Assessed using resting-state fMRI to quantify the acute and long-term regulatory effects of TIS on the basal ganglia-thalamus-cortical circuit.

Time frame: Baseline, 20 minutes (during concurrent TIS), and 8 minutes (immediately post-stimulation) for Phase A ; Baseline and 2 weeks for Phase B.