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

NCT07118956 | Recruiting

• 1 other identifier: PD-TaVNS-RCT
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson Disease; Apathy; Non-motor Symptoms; Vagus Nerve Stimulation

Keywords

Parkinson Disease; Apathy; Non-motor symptoms; Transcutaneous Auricular Vagus Nerve Stimulation

Outcome Measures

Primary Outcomes (1)

• Apathy Motivation Index (AMI)

  The AMI is used to assess levels of apathy across behavioral, emotional, and cognitive domains. It provides a comprehensive measure of motivation deficits.

  baseline; 2 weeks; 6weeks; 8weeks; 10 weeks

Secondary Outcomes (12)

• Non-Motor Symptoms Scale, Second Version (NMSS-2)

  baseline; 2 weeks; 6weeks; 8weeks; 10 weeks

• AMI subscales

  baseline; 2 weeks; 6weeks; 8weeks; 10 weeks

• Epworth Sleepiness Scale (ESS)

  baseline; 2 weeks; 10 weeks

• Fatigue Scale-14 (FS-14)

  baseline; 2 weeks; 10 weeks

• Pittsburgh Sleep Quality Index (PSQI)

  baseline; 2 weeks; 10 weeks

Study Arms (2)

Active respiratory-gated transcutaneous auricular vagus nerve stimulation (RAVANS)

EXPERIMENTAL

Participants will receive active RAVANS daily for 2 week.

Other: Active RAVANS

Sham RAVANS

SHAM COMPARATOR

Participants will receive sham RAVANS daily for 2 week.

Other: Sham RAVANS

Interventions

Active RAVANS OTHER

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.

Also known as: RAVANS

Active respiratory-gated transcutaneous auricular vagus nerve stimulation (RAVANS)

Sham RAVANS OTHER

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.

Also known as: RAVANS

Sham RAVANS

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Anhui Medical University: lead

Study Sites (1)

Cognitive Neuropsychology Lab Anhui Medical University

Hefei, Anhui, 230022, China

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Lethargy

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Kai Wang, Ph.D.

  Anhui Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rong Ye, Ph.D.

CONTACT

+8615656050129; ronye.uk@gmail.com

Panpan Hu, Ph.D.

CONTACT

+8655162923704; hpppanda9@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Department, Department of Neurology, The First Affiliated Hospital of Anhui Medical University

Study Record Dates

• First Submitted: May 19, 2025
• First Posted: August 12, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: November 19, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)