Back to resultsCurative Effect and Mechanism of Transcutaneous Auricular Vagus Nerve Stimulation on Non-motor Symptoms of PD
Primary Purpose
Parkinson Disease
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Transcutaneous auricular vagus nerve stimulation (real stimulation)
Transcutaneous auricular vagus nerve stimulation (sham stimulation)
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson Disease focused on measuring non-motor symptoms, Therapeutics
Eligibility Criteria
Inclusion Criteria: Idiopathic Parkinson's disease (PD), as diagnosed by a neurologist. PDSS score<82 (or a subscore<5). Age between 40 and 80 years old. Mini-Mental State Examination score >24. Right-handed patient. Stable medication. Exclusion Criteria: Clinically diagnosed as other Parkinson's syndrome. Cognitive impairment (MMSE<24), severe anxiety and depression, epilepsy history, severe diabetes, organic brain stem injury (such as stroke, tumor, demyelinating disease, etc.). Taking anticholinergic drugs. Taking antipsychotic drugs. There are contraindications to taVNS stimulation, such as implantation of a cardiac pacemaker after DBS operation, patients with local infection or loss of an ear, or metal implants at the stimulation site. There is uncontrolled hypertension, coronary heart disease, or recent acute myocardial infarction. Patients who cannot complete follow-up.
Sites / Locations
- the First Affiliated Hospital of Nanjing Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
active transcutaneous auricular vagus nerve stimulatio
sham transcutaneous auricular vagus nerve stimulation
Arm Description
For Experimental Arm, active transcutaneous auricular vagus nerve stimulation, Patients underwent fourteen consecutive daily sessions of taVNS.
For sham transcutaneous auricular vagus nerve stimulation arm, Sham Comparator, patients underwent fourteen consecutive daily sessions of sham-taVNS (the electrodes were fixed at the left earlobe with the same stimulation parameters).
Outcomes
Primary Outcome Measures
Changes of non-motor symptom scale
Non-motor symptoms such as sleep disorders were evaluated by Parkinson's disease sleep scale (PDSS). The minimum and maximum values of the non-motor part of the PDSS Scale are 0 and 150. A lower score means a worse outcome.
Changes of sleep quality scale
Non-motor symptoms such as sleep disorders were evaluated by Parkinson's disease sleep scale-2 (PDSS-2). PDSS-2 is an improved version of PDSS used to screen for common types of sleep disorders in Parkinson's disease patients. The minimum and maximum values of the non-motor part of the PDSS-2 Scale are 0 and 60. A higher score means a worse outcome.
Changes of Rapid-eye-movement Sleep Behavior Disorder scale
Rapid-eye-movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was used to assess the behavior disorder of multiple eye movement sleep. The minimum and maximum values of the non-motor part of the RBDSQ Scale are 0 and 13. A higher score means a worse outcome.
Secondary Outcome Measures
The motor part of the Unified Parkinson's Disease Rating Scale
The measure mainly reflects the overall severity of Parkinson's disease motor symptoms. The minimum and maximum values of the motor part of the Unified Parkinson's Disease Rating Scale are 0 and 108. A higher score means a worse outcome.
Serological indicators
5ml of the patient's elbow vein blood was collected and centrifuged after standing and stratified. The serum was collected and frozen at - 20 ℃ for testing. Detection of inflammatory factors indicators.
Resting motor threshold (RMT)
RMT (% TMS output intensity) is defined as the lowest intensity required to elicit MEPs of > 50 μV in at least 5 of 10 consecutive trials while the target muscle is relaxed. RMT was determined to be the nearest 1% of the maximum stimulator output.
Cortical silent period (CSP)
The CSP (ms) is measured through electromyographic signal recording (EMG) on a target muscle and refers to the period of EMG silence following the elicitation of a motor-evoked potential (MEP) through a single TMS pulse delivered over the contralateral primary motor cortex.
Individuals were asked to actively contract abductor pollicis brevis (APB) with 20% of the maximum force, while a single pulse with 150% of RMT was applied to the opposite primary motor cortex. We recorded the time from pulse outputting to the recovery of inhibited active contraction as CSP. The above protocol was repeated ten times, and the average value of CSP was calculated.
Short interval intracortical inhibition (SICI)
SICI was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with a 4ms interstimulus interval between conditioning and test stimuli. Ten trials were acquired for each interstimulus interval. SICI was expressed as the percentage ratio between the test and conditioning MEP.
Intracortical facilitation (ICF)
ICF was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with a 15 ms interstimulus interval between conditioning and test stimuli. Ten trials were acquired for each interstimulus interval. ICF was expressed as the percentage ratio between the test and conditioning MEP.
Changes in ΔHbO2 concentration in the brain cortex
The ΔHbO2 concentration in the brain cortex will be recorded in oxyhemoglobin.
Changes in the cognitive changes
The changes of patients' cognition were evaluated with mini-mental state examination (MMSE) scales. The minimum and maximum values of the non-motor part of the MMSE Scale are 0 and 30. The test scores are closely related to cultural level, and the normal threshold classification criteria are: illiteracy>17 points, primary school>20 points, and middle school and above>24 points. Below the boundary value, there is a cognitive impairment, while above is normal.
Change of anxiety level of patients
The anxiety level of patients was assessed with Hamilton anxiety scale (HAMA) scale. The minimum and maximum values of the non-motor part of the HAMA Scale are 0 and 56. A higher score means a worse outcome.
Changes in depression level of patients
The change of patients' depression level was evaluated with Hamilton Depression Scale 24 (HAMD-24) scale. The minimum and maximum values of the non-motor part of the HAMD Scale are 0 and 96. A higher score means a worse outcome.
Changes in sleep quality, sleep efficiency and other sleep indicators of patients
The changes of patients' sleep quality, sleep efficiency and other sleep indicators were evaluated with Epworth Sleepiness Scale (ESS) scales. ESS scale used to evaluate daytime drowsiness. The minimum and maximum values of the non-motor part of the ESS Scale are 0 and 24. A higher score means a worse outcome.
Changes in patients' fatigue
The fatigue degree of patients was evaluated with Fatigue Severity Scale (FSS) scale. The minimum and maximum values of the non-motor part of the FSS Scale are 7 and 63. A higher score means a worse outcome.
Changes in patients' anxiety level
The change of patients' anxiety was evaluated with apathy scale (AS) scale. The minimum and maximum values of the non-motor part of the AS Scale are 0 and 27. A higher score means a worse outcome.
Changes in the cognitive degree
The change of cognitive degree of patients was evaluated with Montreal Cognitive Assessment (MoCA) scale. The total score of the MoCA scale is 30, generally 26 points or higher is considered normal, between 18-26 points is considered mild cognitive impairment, between 10-17 points is moderate cognitive impairment, and less than 10 points is severe cognitive impairment. If the assessed person has less than or equal to 12 years of education, they are generally only at the high school level, and the result can be increased by 1 point, but the total score cannot exceed 30 points.
Plasma indicators
5ml of the patient's elbow vein blood was collected and centrifuged after standing and stratified. The blood plasma was collected and frozen at - 20 ℃ for testing. Detection of changes in plasma ghrelin levels.
Changes in sleep quality, sleep efficiency of patients
Pittsburgh sleep quality index (PSQI) was used to evaluate the sleep quality of participants in the past month. It consists of 19 self-evaluation and 5 other evaluation items. The total score range is 0-21, with higher scores indicating poorer sleep quality.
Full Information
NCT ID
NCT05806736
First Posted
February 27, 2023
Last Updated
April 7, 2023
Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
National Natural Science Foundation of China
1. Study Identification
Unique Protocol Identification Number
NCT05806736
Brief Title
Curative Effect and Mechanism of Transcutaneous Auricular Vagus Nerve Stimulation on Non-motor Symptoms of PD
Official Title
Study on the Efficacy and Mechanism of Transcutaneous Auricular Vagus Nerve Stimulation in the Treatment of Non-motor Symptoms of Parkinson's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2022 (Actual)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
July 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
National Natural Science Foundation of China
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is a double-blind comparative study examining the curative effect and mechanism of the transcutaneous auricular vagus nerve stimulation treatment on non-motor symptoms of Parkinson's disease patients. The investigators hypothesize that treatment using transcutaneous auricular vagus nerve stimulation will improve the non-motor symptoms, such as improving sleep, and improve cortical activity simultaneously in Parkinson's disease patients.
Detailed Description
Patients in the Experimental group underwent fourteen consecutive daily sessions of transcutaneous auricular vagus nerve stimulation (taVNS, twice daily, 30 minutes each time), whereas patients in the sham stimulation group underwent fourteen consecutive daily sessions of sham taVNS. Assessments of motor and non-motor symptoms, excitability of cortex motor (using repetitive transcranial magnetic stimulation), cortical activity (using Functional near-infrared spectroscopy) and blood indicators were performed three times: at baseline, one day post intervention, fourteen days post intervention.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
Keywords
non-motor symptoms, Therapeutics
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Masking Description
Double (Participant, Outcomes Assessor)
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
active transcutaneous auricular vagus nerve stimulatio
Arm Type
Experimental
Arm Description
For Experimental Arm, active transcutaneous auricular vagus nerve stimulation, Patients underwent fourteen consecutive daily sessions of taVNS.
Arm Title
sham transcutaneous auricular vagus nerve stimulation
Arm Type
Sham Comparator
Arm Description
For sham transcutaneous auricular vagus nerve stimulation arm, Sham Comparator, patients underwent fourteen consecutive daily sessions of sham-taVNS (the electrodes were fixed at the left earlobe with the same stimulation parameters).
Intervention Type
Device
Intervention Name(s)
Transcutaneous auricular vagus nerve stimulation (real stimulation)
Intervention Description
Transcutaneous auricular vagus nerve stimulation was conducted by transcutaneous electrical stimulation therapy instrument to the cymba conchae of left ear in the vicinity of the auricular branch vagus nerve. Stimulation parameters: frequency = 20/4 Hz; pulse width = 200 μs, twice a day, 30 minutes each time.
Intervention Type
Device
Intervention Name(s)
Transcutaneous auricular vagus nerve stimulation (sham stimulation)
Intervention Description
Transcutaneous auricular vagus nerve stimulation was conducted by transcutaneous electrical stimulation therapy instrument to the left earlobe. Stimulation parameters: frequency = 20/4 Hz; pulse width = 200 μs, twice a day, 30 minutes each time.
Primary Outcome Measure Information:
Title
Changes of non-motor symptom scale
Description
Non-motor symptoms such as sleep disorders were evaluated by Parkinson's disease sleep scale (PDSS). The minimum and maximum values of the non-motor part of the PDSS Scale are 0 and 150. A lower score means a worse outcome.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Changes of sleep quality scale
Description
Non-motor symptoms such as sleep disorders were evaluated by Parkinson's disease sleep scale-2 (PDSS-2). PDSS-2 is an improved version of PDSS used to screen for common types of sleep disorders in Parkinson's disease patients. The minimum and maximum values of the non-motor part of the PDSS-2 Scale are 0 and 60. A higher score means a worse outcome.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Changes of Rapid-eye-movement Sleep Behavior Disorder scale
Description
Rapid-eye-movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was used to assess the behavior disorder of multiple eye movement sleep. The minimum and maximum values of the non-motor part of the RBDSQ Scale are 0 and 13. A higher score means a worse outcome.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Secondary Outcome Measure Information:
Title
The motor part of the Unified Parkinson's Disease Rating Scale
Description
The measure mainly reflects the overall severity of Parkinson's disease motor symptoms. The minimum and maximum values of the motor part of the Unified Parkinson's Disease Rating Scale are 0 and 108. A higher score means a worse outcome.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Serological indicators
Description
5ml of the patient's elbow vein blood was collected and centrifuged after standing and stratified. The serum was collected and frozen at - 20 ℃ for testing. Detection of inflammatory factors indicators.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Resting motor threshold (RMT)
Description
RMT (% TMS output intensity) is defined as the lowest intensity required to elicit MEPs of > 50 μV in at least 5 of 10 consecutive trials while the target muscle is relaxed. RMT was determined to be the nearest 1% of the maximum stimulator output.
Time Frame
Assessed at baseline, one day post intervention.
Title
Cortical silent period (CSP)
Description
The CSP (ms) is measured through electromyographic signal recording (EMG) on a target muscle and refers to the period of EMG silence following the elicitation of a motor-evoked potential (MEP) through a single TMS pulse delivered over the contralateral primary motor cortex.
Individuals were asked to actively contract abductor pollicis brevis (APB) with 20% of the maximum force, while a single pulse with 150% of RMT was applied to the opposite primary motor cortex. We recorded the time from pulse outputting to the recovery of inhibited active contraction as CSP. The above protocol was repeated ten times, and the average value of CSP was calculated.
Time Frame
Assessed at baseline, one day post intervention.
Title
Short interval intracortical inhibition (SICI)
Description
SICI was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with a 4ms interstimulus interval between conditioning and test stimuli. Ten trials were acquired for each interstimulus interval. SICI was expressed as the percentage ratio between the test and conditioning MEP.
Time Frame
Assessed at baseline, one day post intervention.
Title
Intracortical facilitation (ICF)
Description
ICF was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with a 15 ms interstimulus interval between conditioning and test stimuli. Ten trials were acquired for each interstimulus interval. ICF was expressed as the percentage ratio between the test and conditioning MEP.
Time Frame
Assessed at baseline, one day post intervention.
Title
Changes in ΔHbO2 concentration in the brain cortex
Description
The ΔHbO2 concentration in the brain cortex will be recorded in oxyhemoglobin.
Time Frame
Assessed at baseline, one day post intervention.
Title
Changes in the cognitive changes
Description
The changes of patients' cognition were evaluated with mini-mental state examination (MMSE) scales. The minimum and maximum values of the non-motor part of the MMSE Scale are 0 and 30. The test scores are closely related to cultural level, and the normal threshold classification criteria are: illiteracy>17 points, primary school>20 points, and middle school and above>24 points. Below the boundary value, there is a cognitive impairment, while above is normal.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Change of anxiety level of patients
Description
The anxiety level of patients was assessed with Hamilton anxiety scale (HAMA) scale. The minimum and maximum values of the non-motor part of the HAMA Scale are 0 and 56. A higher score means a worse outcome.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Changes in depression level of patients
Description
The change of patients' depression level was evaluated with Hamilton Depression Scale 24 (HAMD-24) scale. The minimum and maximum values of the non-motor part of the HAMD Scale are 0 and 96. A higher score means a worse outcome.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Changes in sleep quality, sleep efficiency and other sleep indicators of patients
Description
The changes of patients' sleep quality, sleep efficiency and other sleep indicators were evaluated with Epworth Sleepiness Scale (ESS) scales. ESS scale used to evaluate daytime drowsiness. The minimum and maximum values of the non-motor part of the ESS Scale are 0 and 24. A higher score means a worse outcome.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Changes in patients' fatigue
Description
The fatigue degree of patients was evaluated with Fatigue Severity Scale (FSS) scale. The minimum and maximum values of the non-motor part of the FSS Scale are 7 and 63. A higher score means a worse outcome.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Changes in patients' anxiety level
Description
The change of patients' anxiety was evaluated with apathy scale (AS) scale. The minimum and maximum values of the non-motor part of the AS Scale are 0 and 27. A higher score means a worse outcome.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Changes in the cognitive degree
Description
The change of cognitive degree of patients was evaluated with Montreal Cognitive Assessment (MoCA) scale. The total score of the MoCA scale is 30, generally 26 points or higher is considered normal, between 18-26 points is considered mild cognitive impairment, between 10-17 points is moderate cognitive impairment, and less than 10 points is severe cognitive impairment. If the assessed person has less than or equal to 12 years of education, they are generally only at the high school level, and the result can be increased by 1 point, but the total score cannot exceed 30 points.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Plasma indicators
Description
5ml of the patient's elbow vein blood was collected and centrifuged after standing and stratified. The blood plasma was collected and frozen at - 20 ℃ for testing. Detection of changes in plasma ghrelin levels.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
Title
Changes in sleep quality, sleep efficiency of patients
Description
Pittsburgh sleep quality index (PSQI) was used to evaluate the sleep quality of participants in the past month. It consists of 19 self-evaluation and 5 other evaluation items. The total score range is 0-21, with higher scores indicating poorer sleep quality.
Time Frame
Assessed at baseline, one day post intervention, fourteen days post intervention.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Idiopathic Parkinson's disease (PD), as diagnosed by a neurologist.
PDSS score<82 (or a subscore<5).
Age between 40 and 80 years old.
Mini-Mental State Examination score >24.
Right-handed patient.
Stable medication.
Exclusion Criteria:
Clinically diagnosed as other Parkinson's syndrome.
Cognitive impairment (MMSE<24), severe anxiety and depression, epilepsy history, severe diabetes, organic brain stem injury (such as stroke, tumor, demyelinating disease, etc.).
Taking anticholinergic drugs.
Taking antipsychotic drugs.
There are contraindications to taVNS stimulation, such as implantation of a cardiac pacemaker after DBS operation, patients with local infection or loss of an ear, or metal implants at the stimulation site.
There is uncontrolled hypertension, coronary heart disease, or recent acute myocardial infarction.
Patients who cannot complete follow-up.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kezhong Zhang
Phone
13770840575
Email
kezhong_zhang1969@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kezhong Zhang
Organizational Affiliation
The First Affiliated Hospital with Nanjing Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
the First Affiliated Hospital of Nanjing Medical University
City
Nanjing
State/Province
Jiang Su
ZIP/Postal Code
210029
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kezhong Zhang
Phone
13770840575
Email
kezhong_zhang1969@126.com
12. IPD Sharing Statement
Plan to Share IPD
No
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Curative Effect and Mechanism of Transcutaneous Auricular Vagus Nerve Stimulation on Non-motor Symptoms of PD
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