Ameliorating Effects and Mechanisms of TaVNS on Constipation in PD Patients.

Not Applicable

Not yet recruiting

• Conditions: Parkinson Disease, Idiopathic; Constipation
• Interventions: Device: active Transcutaneous auricular vagus nerve stimulation; Device: sham Transcutaneous auricular vagus nerve stimulation

• Registration Number: NCT06623591
• Lead Sponsor: Kezhong Zhang

Brief Summary

The investigators intend to conduct a randomized, double-blind, sham-stimulation-controlled experiment, incorporating various clinical scales, gastrointestinal electrogram, and high-resolution anorectal manometry (HRAM), to investigate the improvement effect of taVNS on constipation symptoms in PD patients.

Detailed Description

The investigators intend to conduct a randomized, double-blind, sham-stimulation-controlled experiment, incorporating various clinical scales, gastrointestinal electrogram, and high-resolution anorectal manometry (HRAM), to investigate the improvement effect of taVNS on constipation symptoms in PD patients. Meanwhile, the investigators aimed to verify mechanistic effects by investigating changes in proteins and cytokines related to inflammation and intestinal barrier function in serum and feces to verify mechanistic effects.

Study Timeline

• Study First Submitted: 2024-09-30
• Study First Submitted QC: 2024-09-30
• Status Verified: 2024-10
• Study First Posted: 2024-10-02
• Last Update Submitted: 2024-10-03
• Last Update Posted: 2024-10-04
• Study Start: 2024-10-15
• Primary Completion: 2024-11-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. aged 40-70 years;
2. had a PD diagnosis designated by movement disorder neurologists (Ke-zhong Zhang and Yong-sheng Yuan) according to Movement Disorder Society Clinical Diagnostic Criteria;
3. fulfilled Rome IV criteria for functional constipation, including having < 3 spontaneous bowel movements (SBM; i.e., not induced by rescue medication) per week for the past 3 months with symptom duration of at least 6 months;
4. stable initiation of PD medications, leastways 3 month before this investigation; (5) provided written informed consent.

Exclusion Criteria

1. a history of previous abdominal surgery (other than appendectomy);
2. the presence of carcinoma;
3. any organic diseases causing constipation or neurologic diseases such as multiple sclerosis, rachischisis, or spinal cord injury;
4. taking antidepressant agents including tricyclic antidepressants and selective serotonin reuptake inhibitors;
5. a serious concomitant disease of the heart, liver, kidney, or diabetes;
6. pregnancy or lactation;
7. participating in another trial or enrolled in a trial during the past month;
8. an allergic reaction to surface electrodes.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Transcutaneous auricular vagus nerve stimulation	active Transcutaneous auricular vagus nerve stimulation	For Experimental Arm, active transcutaneous auricular vagus nerve stimulation, Patients underwent 28 consecutive daily sessions of taVNS.
Sham Transcutaneous auricular vagus nerve stimulation	sham Transcutaneous auricular vagus nerve stimulation	For sham transcutaneous auricular vagus nerve stimulation arm, Sham Comparator, patients underwent 28 consecutive daily sessions of sham-taVNS (the electrodes were fixed at the the left earlobe).

Primary Outcome Measures

Name	Time	Method
alterations in complete spontaneous bowel movements per week (CSBMs/week)	Assessed at 2 weeks before baseline, 2 weeks before the last day of intervention	By having patients record their bowel movements two weeks before the start of the experiment and two weeks before the end of the experiment, calculate the CSBMs/week.

Secondary Outcome Measures

Name	Time	Method
Change from Baseline Gastrointestinal Dysfunction Scale for Parkinson's Disease (GIDS-PD) at one day post intervention	Assessed at baseline, one day post intervention	The Gastrointestinal Dysfunction Scale for Parkinson\'s Disease is a novel disease-specific self-report tool to quantitatively assess the presence and severity of gastrointestinal dysfunction features in patients with PD, with strong reliability and validity. The GIDS-PD (Appendix S1) is a Likert self-report scale composed of 12 items. The total score of the GIDS-PD is computed by adding the total score of items 1 through 12, resulting in a minimum score of 1 and a maximum score of 108.
Change from Baseline Gastrointestinal Symptoms Rating Scales at one day post intervention	Assessed at baseline, one day post intervention	Used to evaluate the gastrointestinal symptoms and discomfort level of patients, from 0 to 105.
Change from Baseline constipation symptoms scores at one day post intervention	Assessed at baseline, one day post intervention	Used to evaluate the constipation symptoms , from 0 to 30.
Change from Baseline Patient Assessment of Constipation Quality of Life scale，PAC-QOL at one day post intervention	Assessed at baseline, one day post intervention	Used to evaluate quality of life, a total of 28 items are divided into 4 aspects: physiological discomfort, psychological discomfort, palpitations, and satisfaction. The PAC-QOL score range is 0-4, with lower scores indicating better results.
Change from Baseline Patient Assessment of Constipation Symptoms questionnaire at one day post intervention	Assessed at baseline, one day post intervention	Used to evaluate the constipation symptoms , from 0 to 48.
Change from Baseline HRAM at one day post intervention--Resting pressure (mmHg)	Assessed at baseline, one day post intervention	Following HRV test, HRAM was undertaken using a solid-state manometric instrument with 12 circumferential sensors spaced at 1 cm intervals and an outer diameter of 4.2 mm to evaluate anorectal sensorimotor function. Patients were asked to be in the left lateral position with the hips and knees flexed, and then the solid-state catheter was inserted into the rectum through the anal orifice. After a 3-minute period of stabilization, the sequential maneuver procedures are as follows: Resting pressure (mmHg), maximum squeeze pressure (mmHg). First-sensation volume, desire to defecate threshold, and maximum tolerance were tested by constant dilation of balloon
Change from Baseline HRAM at one day post intervention--maximum squeeze pressure (mmHg)	Assessed at baseline, one day post intervention	Following HRV test, HRAM was undertaken using a solid-state manometric instrument with 12 circumferential sensors spaced at 1 cm intervals and an outer diameter of 4.2 mm to evaluate anorectal sensorimotor function. Patients were asked to be in the left lateral position with the hips and knees flexed, and then the solid-state catheter was inserted into the rectum through the anal orifice. After a 3-minute period of stabilization, the sequential maneuver procedures are as follows: Resting pressure (mmHg), maximum squeeze pressure (mmHg). First-sensation volume, desire to defecate threshold, and maximum tolerance were tested by constant dilation of balloon
Change from Baseline HRAM at one day post intervention--First sensation (mL)	Assessed at baseline, one day post intervention	Following HRV test, HRAM was undertaken using a solid-state manometric instrument with 12 circumferential sensors spaced at 1 cm intervals and an outer diameter of 4.2 mm to evaluate anorectal sensorimotor function. Patients were asked to be in the left lateral position with the hips and knees flexed, and then the solid-state catheter was inserted into the rectum through the anal orifice. After a 3-minute period of stabilization, the sequential maneuver procedures are as follows: Resting pressure (mmHg), maximum squeeze pressure (mmHg). First-sensation volume, desire to defecate threshold, and maximum tolerance were tested by constant dilation of balloon
Change from Baseline HRAM at one day post intervention--desire to defecate threshold	Assessed at baseline, one day post intervention	Following HRV test, HRAM was undertaken using a solid-state manometric instrument with 12 circumferential sensors spaced at 1 cm intervals and an outer diameter of 4.2 mm to evaluate anorectal sensorimotor function. Patients were asked to be in the left lateral position with the hips and knees flexed, and then the solid-state catheter was inserted into the rectum through the anal orifice. After a 3-minute period of stabilization, the sequential maneuver procedures are as follows: Resting pressure (mmHg), maximum squeeze pressure (mmHg). First-sensation volume, desire to defecate threshold, and maximum tolerance were tested by constant dilation of balloon
Change from Baseline HRAM at one day post intervention--maximum tolerance	Assessed at baseline, one day post intervention	Following HRV test, HRAM was undertaken using a solid-state manometric instrument with 12 circumferential sensors spaced at 1 cm intervals and an outer diameter of 4.2 mm to evaluate anorectal sensorimotor function. Patients were asked to be in the left lateral position with the hips and knees flexed, and then the solid-state catheter was inserted into the rectum through the anal orifice. After a 3-minute period of stabilization, the sequential maneuver procedures are as follows: Resting pressure (mmHg), maximum squeeze pressure (mmHg). First-sensation volume, desire to defecate threshold, and maximum tolerance were tested by constant dilation of balloon
Change from Baseline gastrointestinal electrogram at one day post intervention--amplitude	Assessed at baseline, one day post intervention	A total of 8 leads cover the body surface projection of the stomach and intestines, which can reflect the gastrointestinal motility
Change from Baseline gastrointestinal electrogram at one day post intervention--frequency	Assessed at baseline, one day post intervention	A total of 8 leads cover the body surface projection of the stomach and intestines, which can reflect the gastrointestinal motility.
Change from Baseline serum indicators at one day post intervention	Assessed at baseline, one day post intervention	A blood sample was taken at 8 a.m. at baseline and after 4 weeks of treatment. For each patient, about 5 mL of blood was drawn into a procoagulant tube and 4 mL into 2 anticoagulant tubes with EDTA; it was centrifuged at 4°C and 1139g for 10 minutes and 5 minutes respectively. The serum in the procoagulant tube was divided into 3 portions, and the plasma in the anticoagulant tubes was divided into 2 portions - each about 0.5 mL - and placed at -80°C for assay within 6 months.
Change from Baseline feces indicators at one day post intervention	Assessed at baseline, one day post intervention	placed at -80°C for assay within 6 months.
Change from Baseline The motor part of the Unified Parkinson's Disease Rating Scale at one day post intervention	Assessed at baseline, one day post intervention	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.