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

March 20, 2026 updated by: Weiguo Liu, Jiangsu Province Nanjing Brain Hospital

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

75

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Nanjing Brain Hospital (Affiliated Brain Hospital of Nanjing Medical University)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 130 Hz TIS Group
Participants receive active Temporal Interference Stimulation (TIS) with a 130 Hz envelope frequency targeting the right globus pallidus internus (GPi).
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).
Experimental: 40 Hz TIS Group
Participants receive active TIS with a 40 Hz envelope frequency targeting the right GPi.
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.
Sham Comparator: Sham Group
Participants receive sham stimulation targeting the right GPi.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
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.
Baseline, 2 weeks (immediately after the 10th intervention session), and 1 month (follow-up).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Assessed using resting-state fMRI to quantify the acute and long-term regulatory effects of TIS on the basal ganglia-thalamus-cortical circuit.
Baseline, 20 minutes (during concurrent TIS), and 8 minutes (immediately post-stimulation) for Phase A ; Baseline and 2 weeks for Phase B.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jiangsu Province Nanjing Brain Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 20, 2026

Primary Completion (Estimated)

August 31, 2026

Study Completion (Estimated)

March 31, 2027

Study Registration Dates

First Submitted

March 14, 2026

First Submitted That Met QC Criteria

March 14, 2026

First Posted (Actual)

March 18, 2026

Study Record Updates

Last Update Posted (Actual)

March 24, 2026

Last Update Submitted That Met QC Criteria

March 20, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-KY020-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared to protect the privacy of the patients and because the data is currently being used for institutional research and future academic publications.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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