Effect of Transcutaneous Auricular Vagal Nerve Stimulation on Chronic Constipation

Effect of Transcutaneous Auricular Vagal Nerve Stimulation on Chronic Constipation: A Randomized Controlled Trial

The worldwide prevalence of chronic constipation (CC) is 15%, and women are more likely to develop the disease than men. CC have a significant impact on quality of life and increase the burden of national health insurance. The conventional medication treatments are primarily symptom-specific and have limited efficacy. Previous small sample study had shown the therapeutic potential of transcutaneous auricular vagus nerve stimulation (taVNS) for irritable bowel syndrome with constipation (IBS-C). The aim of this study was to investigate whether taVNS could improve defecation condition and constipation symptoms in patients with CC.

Study Overview

• Status: Recruiting
• Conditions: Chronic Constipation
• Intervention / Treatment: Device: taVNS; Drug: Laxative Agent

• Study Type: Interventional
• Enrollment (Anticipated): 210
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yanglin Pan, M.D; Phone Number: 13991811225; Email: yanglinpan@hotmail.com

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • Recruiting
      • Department of Gastroenterology, Second Affiliated Hospital, Lanzhou University
      • Contact: Xiaojun Huang, MD; Phone Number: +8609318942279; Email: haungxj62@163.com
  • Guangdong
    • Shenzhen, Guangdong, China, 518114
      • Recruiting
      • Department of Gastroenterology, National Clinical Research Center of Infectious Disease, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology
      • Contact: Xiaoyin Zhang; Email: xhnk-01@szsy.sustech.edu.cn
  • Shaanxi
    • Xi'an, Shaanxi, China, 710038
      • Recruiting
      • Tangdu Hospital
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Endoscopic center, Xijing Hospital of Digestive Diseases
      • Contact: Yanlin Pan, M.D.; Phone Number: 86-29-84771536; Email: yanglinpan@hotmail.com
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing 986 Hospita

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. FC or IBS-C patients aged 18-75 years who meet the diagnostic criteria for Rome IV;
2. Complete spontaneous bowel movements (CSBMs) per week < 3;
3. No constipation medication used for at least 2 weeks prior to enrollment, not participated in clinical trials in the past three months, and no abnormal colonoscopy within the past 12 months in those with alarm symptoms.

Exclusion Criteria:

1. Have cognitive impairment, psychiatric disorders, or conditions that may affect patient cooperation;
2. Have a cardiac pacemaker implantation or other electronically implanted devices;
3. Prior taVNS treatment;
4. History of colorectal surgery, except for simple appendectomy;
5. Severe cardiovascular, hepatic, or renal disease;
6. Known malignancy;
7. Secondary constipation caused by medications and other diseases;
8. Pregnant or lactating women;
9. Refusal to sign an informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment group; patients will receive taVNS at left tragus for four weeks.	Device: taVNS; Patients will receive taVNS (device produced by Xi'an Bashui Health Technology Co., Ltd) thirty minutes twice a day in the morning and the night for four weeks (duty circle: 30s "on" periods and 30s "off" periods; frequency: 25 Hz; amplitude of 0-2 mA at the maximum level that the patient could tolerate; pulse width: 0.5ms); Drug: Laxative Agent; Bisacodyl or glycerin enemas can be used in patients who do not have a bowel movement for more than 3 days.
SHAM_COMPARATOR: Sham-treatment group; patients will receive sham-taVNS at left earlobe for four weeks.	Device: taVNS; Patients will receive taVNS (device produced by Xi'an Bashui Health Technology Co., Ltd) thirty minutes twice a day in the morning and the night for four weeks (duty circle: 30s "on" periods and 30s "off" periods; frequency: 25 Hz; amplitude of 0-2 mA at the maximum level that the patient could tolerate; pulse width: 0.5ms); Drug: Laxative Agent; Bisacodyl or glycerin enemas can be used in patients who do not have a bowel movement for more than 3 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder rate	Proportion of patients with an average of 3 or more complete spontaneous bowel movements (CSBMs) per week from 1 to 4 weeks	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder rate at the time of the follow-up visit	Proportion of patients with an average of 3 or more CSBMs per week from 5 to 12 weeks	8 weeks
CSBMs	Changes from baseline by time point in the CSBMs	12 weeks
Spontaneous bowel movements (SBMs)	Changes from baseline by time point in the SBMs	12 weeks
Abdominal symptoms	Changes from baseline by time point in abdominal symptoms scores (abdominal bloating, abdominal fullness, abdominal discomfort, abdominal pain, abdominal cramping).	12 weeks
Bristol stool form scale (BFSF)	Changes from baseline by time point in the BFSF	12 weeks
Laxative agents using	Proportion of patients using laxative agents and/or other adjunctive bowel measures at 1-12 weeks and the average number of times per week	12 weeks
Patient Assessment of Constipation symptom (PAC-SYM)	Changes from baseline by time point in the PAC-SYM score	12 weeks
Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL)	Changes from baseline by time point in the PAC-QOL score	12 weeks
Self-Rating Depression Scale (SDS)	Changes from baseline by time point in SDS scores	12 weeks
Self-Rating Anxiety Scale (SAS)	Changes from baseline by time point in SAS scores	12 weeks
Adverse events	Adverse events	12 weeks

Collaborators and Investigators

• Sponsor: Air Force Military Medical University, China

Publications and helpful links

General Publications

• Mugie SM, Benninga MA, Di Lorenzo C. Epidemiology of constipation in children and adults: a systematic review. Best Pract Res Clin Gastroenterol. 2011 Feb;25(1):3-18. doi: 10.1016/j.bpg.2010.12.010.
• Nag A, Martin SA, Mladsi D, Olayinka-Amao O, Purser M, Vekaria RM. The Humanistic and Economic Burden of Chronic Idiopathic Constipation in the USA: A Systematic Literature Review. Clin Exp Gastroenterol. 2020 Jul 16;13:255-265. doi: 10.2147/CEG.S239205. eCollection 2020.
• Shi X, Hu Y, Zhang B, Li W, Chen JD, Liu F. Ameliorating effects and mechanisms of transcutaneous auricular vagal nerve stimulation on abdominal pain and constipation. JCI Insight. 2021 Jul 22;6(14):e150052. doi: 10.1172/jci.insight.150052.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 3, 2023
• Primary Completion (ANTICIPATED): January 31, 2024
• Study Completion (ANTICIPATED): February 28, 2024

Study Registration Dates

• First Submitted: January 31, 2023
• First Submitted That Met QC Criteria: February 9, 2023
• First Posted (ACTUAL): February 13, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: constipation
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Gastrointestinal Agents; Laxatives
• Other Study ID Numbers: KY20222075-F-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Other researchers can contact PI to get IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No