Pain Relief From Dysmenorrhea Employing taVNS (taVNS-DYSM)

A Randomized Two-Way Crossover Comparison Study of Pain Relief From Dysmenorrhea Employing taVNS and Sham Stimulation

The goal of this clinical trial is to determine if transauricular vagal nerve stimulation (taVNS) is effective in treating moderate dysmenorrhea. The main question it aims to answer is:

• Does taVNS reduce the number of times participants suffering from dysmenorrhea need to use rescue medication during menstruation? Researchers will compare taVNS stimulation with a sham stimulation (a look-alike procedure that does not stimulate the vagus nerve) to assess whether taVNS is effective in treating moderate dysmenorrhea.

Participants will:

• Undergo taVNS for 2 months and sham stimulation for another 2 months, each for 5 days per month, starting 2 days before the expected beginning of their menstrual cycle.
• Visit the clinic twice a month for checkups and tests.
• Keep a diary to record their pain levels and the number of times they use rescue medication.
• Undergo functional magnetic resonance imagine two times (one after the end of the first use of taVNS and another after the end of the first use of SHAM stimulation).

Study Overview

• Status: Recruiting
• Conditions: Dysmenorrhea Primary
• Intervention / Treatment: Device: taVNS; Device: SHAM stimulation

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stefania Ferraro, PhD; Phone Number: +86 18684009672; Email: stefania@uestc.edu.cn
• Study Contact Backup: Name: Jaili He; Phone Number: +8615828121558; Email: jiali@uestc.edu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 611731
      • Recruiting
      • UESTC
      • Contact: stefania Ferraro, PhD; Email: stefania@uestc.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Regular menstrual cycle (28 days ± 7 days);
• Average moderate menstrual pain (with 4 - 7 NRS scores);
• History of over-the-counter (OTC) analgesic use for the treatment of menstrual pain (at least 1 IBUPROFEN for the first two days);
• 4 consecutive monthly menstrual cycles;
• Non-pregnant status;
• Agrees to use adequate birth control during the trial;
• Otherwise, healthy;
• Agree not to participate in any other clinical trial while enrolled in this trial ;
• No facial or ear pain, no recent ear trauma, no metal implants including pacemakers;
• Normal ECG, Heart Rate and Blood Pressure (systolic BP 105-130, diastolic BP 60-90, heart rate per min at rest 60-85);

Exclusion Criteria:

• Currently under medications (except for analgesic medication for menstrual cycle);
• Use of oral contraceptive;
• Secondary cause for dysmenorrhea (i.e., endometriosis, adenomyosis, uterine fibroids, or infection);
• Unstable or serious illness (e.g., kidney, liver, GIT, heart conditions, diabetes, thyroid gland function, lung conditions, chronic asthma, diagnosed psychological or mood disorder, hypertension, any bleeding disorders, recent surgery, or concurrent blood thinning treatment);
• Current malignancy or treatment for malignancy within the previous 2 years;
• Pregnant or lactating women;
• Active smokers, nicotine use, or drug (prescription or illegal substances) abuse;
• Chronic past and/or current alcohol use (>14 alcoholic drinks per week);
• Any condition that in the opinion of the investigator, makes the participant unsuitable for inclusion;
• Unwilling or unable to comply with protocol;
• Active genitourinary infection in the last four weeks;
• Unable to read or comprehend the informed consent;
• Unwilling to complete study procedures;
• Participated in any other clinical trial during the past 1 month;
• Personal or family history of seizure, mood, or cardiovascular disorders;
• Allergic reaction to surface electrodes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: taVNS - transauricular vagal nerve stimulation; Transauricular Vagus Nerve Stimulation (taVNS) will be applied in the tragus with the following parameters: Pulse width: 500 microseconds; Frequency: 25 Hz; Stimulation cycle: 30 seconds on, 30 seconds off; Duration: 15 minutes per session; Current: Adjustable between 0 and 10 mA, with step increments of 0.1 mA.	Device: taVNS; Intervention Name: Transauricular Vagus Nerve Stimulation (taVNS) Intervention Description: Participants will receive transauricular vagus nerve stimulation on the tragus. Frequency: 2 sessions per day (one at 10 AM and one at 6 PM). Duration: Each session will last 15 minutes. Treatment Cycle: Stimulation will be applied for 5 days each month, starting 2 days before the expected beginning of the menstrual cycle, for a total of 2 months. The participants will adjust the level of maximum stimulation they considered painless.
Sham Comparator: SHAM stimulation; Stimulation of the earlobe will be applied with the following parameters: Pulse width: 500 microseconds; Frequency: 25 Hz; Stimulation cycle: 30 seconds on, 30 seconds off; Duration: 15 minutes per session; Current: Adjustable between 0 and 10 mA, with step increments of 0.1 mA.	Device: SHAM stimulation; Intervention Name: SHAM stimulation of the earlobe. Participants will receive SHAM stimulation on the earlobe, which does not stimulate the vagus nerve. Frequency: 2 sessions per day (one at 10 AM and one at 6 PM). Duration: Each session will last 15 minutes. Treatment Cycle: Placebo stimulation will be applied for 5 days each month, starting 2 days before the expected beginning of the menstrual cycle, for a total of 2 months. The participants will adjust the level of maximum stimulation they considered painless.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction the use of rescue medications	Significative reduction in the number of cases of rescue medication after the treatment employing the taVNS in respect to the sham condition.	During the first 3 days of menstrual

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in acute and mean menstrual pain severity	Significative reduction in acute and mean (across the 3 days) menstrual pain severity assessed via Numeric Rating Scale (NRS) after the treatment employing the taVNS in respect to the sham condition.	During the first 3 days of menstrual
Reduction in menstrual pain severity at the Short form McGill Pain Questionnarie	Reduction in menstrual pain severity employing using the Short form McGill pain questionnaire during the experimental condition in comparison to the sham condition	During the first 3 days of menstrual
Changes in affective symptoms	Decrease of the score in at least one if the following scale: in Trait Anxiety Inventory (STAI), Beck's Depression Inventory II, Positive and Negative Affect Schedule (PANAS) and Pain Catastrophizing Scale (PCS).	First day of stimulation, last day of stimulation.
Changes in fMRI signal in the mesocorticolimbic system	Changes in fMRI signal in the areas of the mesocorticolimibic system during the execution of a reward fMRI task (Monetary incentive delay task, Kuntson et al., 2001).	After the first month application of the taVNS and of the SHAM stimulation

Collaborators and Investigators

• Sponsor: University of Electronic Science and Technology of China

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: March 24, 2025
• First Submitted That Met QC Criteria: March 30, 2025
• First Posted (Actual): April 4, 2025

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: March 30, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Pain; Dysmenorrhea; transauricular vagal nerve stimulation
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathologic Processes; Pelvic Pain; Menstruation Disturbances; Dysmenorrhea
• Other Study ID Numbers: UESTC-neuSCAN-99; taVNS_DYSM_01 (Other Identifier: UESTC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Primary and secondary outcomes
• IPD Sharing Time Frame: IPD will be available at the end of the relevant analyses with not limit of time.
• IPD Sharing Access Criteria: IPD will be available on the platform OSF
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No