STN-tTIS With Different Intervention Intervals Versus Standard Medical Treatment for Parkinson's Disease

STN-targeted Temporal Interference Stimulation With Different Intervention Intervals Versus Standard Medical Treatment for Parkinson's Disease: A Multicenter, Randomized, Controlled Trial

The goal of this clinical trial is to compare the efficacy and safety of different Intervention Intervals of subthalamic nucleus-targeted transcranial temporal interference stimulation (STN-tTIS) in patients with Parkinson disease.

Previous studies suggest that STN-tTIS may improve motor symptoms in people with Parkinson disease. However, most previous studies evaluated only one stimulation session. It remains unclear how often STN-tTIS should be administered during a repeated treatment course and whether shorter intervention intervals stimulation produces greater or longer-lasting improvement without increasing adverse events.

The main questions this study aims to answer are:

1. Does STN-tTIS administered five times weekly improve motor symptoms more than standard medication treatment alone at the end of the 2-week treatment period?
2. Do once-weekly, twice-weekly, and five-times-weekly STN-tTIS produce different changes in motor symptoms?
3. Does the STN-tTIS intervention intervals influence how long its effects persist after treatment?
4. Do the different intervention intervals have different effects on non-motor symptoms, quality of life, cognitive function, and safety?

Participants will be randomly assigned to receive STN-tTIS once weekly, twice weekly, or five times weekly for 2 weeks, or to continue standard antiparkinsonian medication without additional stimulation. All participants will maintain a stable medication regimen during the study. Their motor and non-motor symptoms will be assessed during the treatment period and during a subsequent 2-week follow-up period.

Inclusion Criteria:

• 1.Aged 50-85 years, male or female.
• 2.Diagnosed with idiopathic Parkinson disease (PD) in accordance with the Chinese Guidelines for the Diagnosis and Treatment of Parkinson's Disease (4th Edition), with a confirmed diagnosis for at least 6 months and a stable condition, defined as no significant deterioration or major medication adjustment within the past month.
• 3.Receiving stable doses of antiparkinsonian medication (e.g., levodopa or dopamine agonists) and willing to maintain the medication regimen during the study.
• 4.Hoehn and Yahr stage 1-3 in the medication ON state.
• 5.Baseline MDS-UPDRS Part III total score ≥20 in the medication ON state.
• 6.No history of non-invasive neuromodulation therapy, or discontinuation of such therapy for at least 3 months before enrollment if previously received.
• 7.Normal cognitive function (MoCA score ≥24) and able to cooperate with tTIS intervention, clinical scale assessments, and basic smartphone- and smartwatch-assisted home-based motor self-assessments.
• 8.Able and willing to provide written informed consent and complete all required study procedures and follow-up assessments.

Exclusion Criteria:

• 1.Other neurological disorders that may affect motor or cognitive function.
• 2.Contraindications to magnetic resonance imaging (MRI), such as claustrophobia.
• 3.History of taking antipsychotics, antidepressants, or other medications affecting dopamine levels.
• 4.Psychiatric disorders (e.g., depression or schizophrenia), substance abuse, or alcohol dependence.
• 5.Implanted medical devices (e.g., pacemaker or defibrillator), metal implants in the cranium or spine, a personal or family history of epilepsy, or severe skull defects.
• 6.Previous deep brain stimulation (DBS) or other intracranial implantation surgery, or participation in another Parkinson disease clinical trial within the past 3 months.