Respiratory-gated Transcutaneous Auricular Vagus Nerve Stimulation for Improving Apathy in Parkinson's Disease

Official title

Respiratory-gated Transcutaneous Auricular Vagus Nerve Stimulation for Improving Apathy in Parkinson's Disease: A Randomized, Double-blind, Sham-controlled Trial

Overview

The goal of this clinical trial is to learn whether 100HZ respiratory-gated vagus nerve stimulation (RAVANS) can improve the non-motor symptoms in people with Parkinson's disease (PD). It will also learn the safety of 100HZ RAVANS. The main questions it aims to answer are: Can 100HZ RAVANS improve apathy in people with PD? Did the participants have any side effects or safety issues when undergoing 100HZ RAVANS? Researchers compared 100HZ RAVANS with sham stimulation (low-dose stimulation of the same site and treatment parameters) to see if 100HZ RAVANS could improve non-motor symptoms in patients with PD. Participants will: Receive 100HZ RAVANS or sham stimulation for 2 weeks. Neuropsychological assessment, imaging and biological sample collection were conducted before and after the entire cycle.

Detailed description

This study employs a double-blind, sham-controlled design to further validate the effects of 100Hz RAVANS on apathy . Patients were randomized into real or sham stimulation groups. Both groups will receive RAVANS once daily, with each session lasting 30 minutes, for a total duration of two weeks. The study design will include neuropsychological assessments, imaging, and biological specimen collection before and after the entire cycle.

Interventions

• Other Active RAVANS
  Real RAVANS was performed on the cymba conchae of left ear in the vicinity of the auricular branch vagus nerve according to the Participant's respiratory rhythm. Stimulation parameters: frequency = 100 Hz; pulse width = 200 us, once a day, 30 minutes each time, one second of stimulation occurs during exhalation.
• Other Sham RAVANS
  Sham RAVANS was performed on on the cymba conchae of left ear according to the Participant's respiratory rhythm. Stimulation parameters: frequency = 100 Hz; pulse width = 200 us, once a day, 30 minutes each time, one second of stimulation occurs during exhalation and the interval between stimulus is 29 seconds.

Primary outcome measures

• Apathy Motivation Index (AMI) [Time frame: baseline; 2 weeks; 6weeks; 8weeks; 10 weeks]

Secondary outcome measures (12)

• Non-Motor Symptoms Scale, Second Version (NMSS-2) [Time frame: baseline; 2 weeks; 6weeks; 8weeks; 10 weeks]
• AMI subscales [Time frame: baseline; 2 weeks; 6weeks; 8weeks; 10 weeks]
• Epworth Sleepiness Scale (ESS) [Time frame: baseline; 2 weeks; 10 weeks]
• Fatigue Scale-14 (FS-14) [Time frame: baseline; 2 weeks; 10 weeks]
• Pittsburgh Sleep Quality Index (PSQI) [Time frame: baseline; 2 weeks; 10 weeks]
• REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) [Time frame: baseline; 2 weeks; 10 weeks]
• The Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) [Time frame: baseline; 2 weeks; 10 weeks]
• The Neuropsychiatric Inventory (NPI) [Time frame: baseline; 2 weeks; 10 weeks]
• The Hamilton Anxiety Rating Scale (HAMA) [Time frame: baseline; 2 weeks; 10 weeks]
• The Hamilton Depression Rating Scale (HAMD) [Time frame: baseline; 2 weeks; 10 weeks]
• Heart Rate Variability (HRV) [Time frame: baseline everyday; during the intervention everyday]
• Behavioral performance and computational parameters in an effort-based decision-making task [Time frame: baseline; 2 weeks]

Eligibility criteria

Inclusion criteria

• Meet the diagnostic criteria for idiopathic Parkinson's disease (based on the MDS Clinical Diagnostic Criteria for Parkinson's Disease (2015 version)).
• Patients with Apathy Motivation Index (AMI) score >1.7.
• All PD patients must be on stable, standardized medication regimens with no adjustments to medications for at least 1 month prior to the study and throughout the study period.
• Demonstrate good compliance and adherence, capable of completing behavioral tests and taVNS therapy.
• Mini-Mental State Examination (MMSE) score ≥22.
• Meet safety criteria for MRI screening.

Exclusion criteria

• Prior brain MRI/CT showing focal brain lesions or severe white matter disease (Fazekas grade 3 or higher).
• Secondary parkinsonism (e.g., vascular parkinsonism, drug-induced parkinsonism).
• History of severe traumatic brain injury, neurosurgery, or deep brain stimulation (DBS) therapy.
• Personal history of epilepsy, unexplained loss of consciousness, or current use of anticonvulsant medications for seizure control.
• Diagnosis of neuropsychiatric disorders other than Parkinson's disease.
• Current use of non-steroidal anti-inflammatory drugs (NSAIDs) or Non-benzodiazepine GABA receptor agonist drug or anticholinergics or corticosteroids, or history of substance abuse or drug addiction.
• Participation in any clinical trial within the past 3 months.
• Severe systemic comorbidities (e.g., hepatic/renal failure, arrhythmias, organic heart disease).
• Pregnant/lactating women or subjects (including males) planning pregnancy within 6 months.
• Contraindications to taVNS, such as cardiac pacemakers, post-DBS surgery, or auricular pathologies (e.g., tympanic membrane perforation).

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

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Cognitive Neuropsychology Lab Anhui Medical University — Hefei

Identifiers

NCT: NCT07118956 · PD-TaVNS-RCT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗