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

Official title

Mechanism of Temporal Interference Stimulation on Brain Networks and Its Long-term Clinical Efficacy in Parkinson's Disease

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.

Detailed description

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.

Interventions

• Device Temporal Interference Stimulation (130 Hz)
  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).
• Device Temporal Interference Stimulation (40 Hz)
  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.
• Device Sham Temporal Interference Stimulation
  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.

Primary outcome measures

• Change from Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) total score. [Time frame: Baseline, 2 weeks (immediately after the 10th intervention session), and 1 month (follow-up).]

Secondary outcome measures (1)

• Changes in Brain Network Functional Connectivity and Amplitude of Low-frequency Fluctuations (ALFF). [Time frame: Baseline, 20 minutes (during concurrent TIS), and 8 minutes (immediately post-stimulation) for Phase A ; Baseline and 2 weeks for Phase B.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Nanjing Brain Hospital (Affiliated Brain Hospital of Nanjing Medical University) — Nanjing

Identifiers

NCT: NCT07480317 · 2026-KY020-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗