Effects of Transcutaneous Vagus Nerve Stimulation (taVNS) in Individuals With Primary Dysmenorrhea

Effects of Transcutaneous Vagus Nerve Stimulation (taVNS) in Individuals With Primary Dysmenorrhea: A Randomized Controlled Study

This study aims to investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on pain, functional and emotional symptoms, and physical performance in individuals with primary dysmenorrhea (PD).

Study Overview

• Status: Completed
• Conditions: Pain; Dysmenorrhea Primary
• Intervention / Treatment: Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS); Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Detailed Description

In this study, which will be conducted over two menstrual cycles, 34 patients with PD will be randomised into two groups: taVNS and sham treatment. From the onset of pain during the menstrual cycle, taVNS or sham treatment will be applied for five days. Pain assessment will be conducted using the Numerical Rating Scale (NRS), pressure pain threshold with an algometer, menstrual symptoms using the Menstrual Symptom Scale (MSS) and the Functional and Emotional Measure of Dysmenorrhea (FEMD), anxiety using the Hamilton Anxiety Scale (HAM-A), and physical performance using the 6-Minute Walk Test (6MWT) during the first and second menstruation.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Artvin, Turkey, 08000
    • Zeynep Yıldız Kızkın

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Being diagnosed with PD according to the No. 345 Primary Dysmenorrhea Consensus Guidelines,
• An NRS score of at least three during menstruation before treatment,
• Being a woman between the ages of 18-40,
• A regular menstrual cycle of 28±7 days,
• Being nulliparous,
• No history of brain surgery, tumour or intracranial metal implantation,
• No chronic genitourinary infection or alcohol or drug use.

Exclusion Criteria:

• History of dizziness or epileptic disease,
• Pregnancy,
• Women with intrauterine devices,
• Metal implants in the head area,
• Women with skin lesions in the area where the electrodes will be placed,
• Use of analgesic drugs during treatment,
• Women with neurological or heart disease,
• Women are diagnosed with gynaecological conditions (endometriosis, adenomyosis, uterine fibroids, etc., which may be associated with secondary dysmenorrhea).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcutaneous Auricular Vagus Nerve Stimulation; Each patient in the Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) group will receive a treatment protocol consisting of taVNS. The treatment will be administered for five days beginning on the first day of pain experienced between the 1st and 2nd menstrual cycles.	Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS); Current will be applied bilaterally from the tragus and turbinate parts of the ear with the VagustimTM device. The current frequency to be used in modulation mode is 10 Hz, and the pulse width is 300 μs (In modulation mode, the pulse rate and width are automatically changed in a loop pattern. The pulse width is reduced by 50% from its original setting in 0.5 seconds; then, the pulse rate is changed in 0.5 seconds, reduced by 50% from the original setting. Total cycle time is 1 second.). The current intensity will be applied for 5 minutes, keeping the current constant where the participant feels comfortable.
Sham Comparator: Sham Transcutaneous Auricular Vagus Nerve Stimulation; Each patient in the sham Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) group will receive a treatment protocol consisting of sham taVNS. The treatment will be administered for five days beginning on the first day of pain experienced between the 1st and 2nd menstrual cycles.	Device: Sham Transcutaneous Auricular Vagus Nerve Stimulation (taVNS); For 5 minutes, sham applications will be applied using a current-free headset specifically designed for this purpose. Participants will observe the device's functionality, but it will not supply any current.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity	Numerical Rating Scale (NRS) data will be queried separately for lower abdominal, waist and bilateral thigh pain. Participants will be required to fill out an NRS questionnaire through the Google Forms web survey platform (Google LLC, Mountain View, CA, USA) before going to bed at night on days 1, 2, and 3 of two consecutive menstrual cycles. The questionnaire will be based on the most severe pain they experienced during the day. The minimum score of the NRS is 0, and the maximum score is 10. Higher scores are associated with more severe pain intensity.	On the 1st menstrual day before the intervention
Pain Intensity	Numerical Rating Scale (NRS) data will be queried separately for lower abdominal, waist and bilateral thigh pain. Participants will be required to fill out an NRS questionnaire through the Google Forms web survey platform (Google LLC, Mountain View, CA, USA) before going to bed at night on days 1, 2, and 3 of two consecutive menstrual cycles. The questionnaire will be based on the most severe pain they experienced during the day. The minimum score of the NRS is 0, and the maximum score is 10. Higher scores are associated with more severe pain intensity.	On the 2nd menstrual day before the intervention
Pain Intensity	Numerical Rating Scale (NRS) data will be queried separately for lower abdominal, waist and bilateral thigh pain. Participants will be required to fill out an NRS questionnaire through the Google Forms web survey platform (Google LLC, Mountain View, CA, USA) before going to bed at night on days 1, 2, and 3 of two consecutive menstrual cycles. The questionnaire will be based on the most severe pain they experienced during the day. The minimum score of the NRS is 0, and the maximum score is 10. Higher scores are associated with more severe pain intensity.	On the 3rd menstrual day before the intervention
Pain Intensity	Numerical Rating Scale (NRS) data will be queried separately for lower abdominal, waist and bilateral thigh pain. Participants will be required to fill out an NRS questionnaire through the Google Forms web survey platform (Google LLC, Mountain View, CA, USA) before going to bed at night on days 1, 2, and 3 of two consecutive menstrual cycles. The questionnaire will be based on the most severe pain they experienced during the day. The minimum score of the NRS is 0, and the maximum score is 10. Higher scores are associated with more severe pain intensity.	On the 1st day of menstruation when the intervention occurred
Pain Intensity	Numerical Rating Scale (NRS) data will be queried separately for lower abdominal, waist and bilateral thigh pain. Participants will be required to fill out an NRS questionnaire through the Google Forms web survey platform (Google LLC, Mountain View, CA, USA) before going to bed at night on days 1, 2, and 3 of two consecutive menstrual cycles. The questionnaire will be based on the most severe pain they experienced during the day. The minimum score of the NRS is 0, and the maximum score is 10. Higher scores are associated with more severe pain intensity.	On the 2nd day of menstruation when the intervention occurred
Pain Intensity	Numerical Rating Scale (NRS) data will be queried separately for lower abdominal, waist and bilateral thigh pain. Participants will be required to fill out an NRS questionnaire through the Google Forms web survey platform (Google LLC, Mountain View, CA, USA) before going to bed at night on days 1, 2, and 3 of two consecutive menstrual cycles. The questionnaire will be based on the most severe pain they experienced during the day. The minimum score of the NRS is 0, and the maximum score is 10. Higher scores are associated with more severe pain intensity.	On the 3rd day of menstruation when the intervention occurred
Pain Pressure Threshold	To measure the pressure pain threshold, it will be used a Push-Pull Force Gauge® (1200-304) will be used by Fabrication Enterprises, Inc. This handheld algometer allows linear force application ranging between 0 and 10 kg (22 lb × ¼ lb and 10 kg × 100 g). Initially, two exercises will be performed on the extensor muscles of the dominant forearm so that patients can become familiar with the equipment. The evaluator will position the algometer perpendicular to each point and apply gradual pressure at a constant rate of approximately 0.5 kg/cm2/s. The pressure will be increased until the participant reports feeling pain. Each point will be evaluated three times, and the average value will be recorded. The measurement will be performed on five reference points in the abdomen and one reference point in the lumbar spine, as in a previous study where pain was evaluated in PD.	On the 1st menstrual day before the intervention
Pain Pressure Threshold	To measure the pressure pain threshold, it will be used a Push-Pull Force Gauge® (1200-304) will be used by Fabrication Enterprises, Inc. This handheld algometer allows linear force application ranging between 0 and 10 kg (22 lb × ¼ lb and 10 kg × 100 g). Initially, two exercises will be performed on the extensor muscles of the dominant forearm so that patients can become familiar with the equipment. The evaluator will position the algometer perpendicular to each point and apply gradual pressure at a constant rate of approximately 0.5 kg/cm2/s. The pressure will be increased until the participant reports feeling pain. Each point will be evaluated three times, and the average value will be recorded. The measurement will be performed on five reference points in the abdomen and one reference point in the lumbar spine, as in a previous study where pain was evaluated in PD.	Immediately after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Menstrual Symptom Scale (MSS)	The scale consists of 22 items and uses a 5-point Likert-type format. Participants are asked to rate the severity of their menstrual symptoms on a scale of 1 (never) to 5 (always). The scale contains three subscales: 'Negative Effects/Somatic Complaints' (items 1-13), 'Menstrual Pain Symptoms' (items 14-19), and 'Coping Methods' (items 20-22). The maximum score on the scale is 110, and the minimum score is 22. MSS score is calculated by taking the average score of all items in the scale. High scores are associated with increased menstrual symptoms.	On the 1st menstrual day before the intervention
Menstrual Symptom Scale (MSS)	The scale consists of 22 items and uses a 5-point Likert-type format. Participants are asked to rate the severity of their menstrual symptoms on a scale of 1 (never) to 5 (always). The scale contains three subscales: 'Negative Effects/Somatic Complaints' (items 1-13), 'Menstrual Pain Symptoms' (items 14-19), and 'Coping Methods' (items 20-22). The maximum score on the scale is 110, and the minimum score is 22. MSS score is calculated by taking the average score of all items in the scale. High scores are associated with increased menstrual symptoms.	Immediately after the intervention
Functional and Emotional Measure of Dysmenorrhea (FEMD)	Functional and Emotional Measure of Dysmenorrhea (FEMD), consisting of 14 items, evaluates dysmenorrhea functionally and emotionally with a 5-point Likert-type item. The reliability and validity study of the scale developed in 2012 was conducted in Turkey in 2015. As the scores obtained from the scale with a minimum score of 14 and a maximum score of 70 increase, the functional and emotional impact of dysmenorrhea also increases.	On the 1st menstrual day before the intervention
Functional and Emotional Measure of Dysmenorrhea (FEMD)	Functional and Emotional Measure of Dysmenorrhea (FEMD), consisting of 14 items, evaluates dysmenorrhea functionally and emotionally with a 5-point Likert-type item. The reliability and validity study of the scale developed in 2012 was conducted in Turkey in 2015. As the scores obtained from the scale with a minimum score of 14 and a maximum score of 70 increase, the functional and emotional impact of dysmenorrhea also increases.	Immediately after the intervention
Hamilton Anxiety Scale (HAM-A)	Patients with chronic pain often experience mood disorders, such as depression and anxiety. The Hamilton Anxiety Scale (HAM-A) will be used to assess the intensity of anxiety symptoms. The scale measures both mental and physical anxiety with 14 symptom-defined items. Each item is scored from 0 (not present) to 4 (severe). The total score range is 0-56. On the anxiety scale, scores of 17 or below indicate mild anxiety, while scores of 18-24 indicate moderate anxiety, and scores of 25-30 indicate severe anxiety.	On the 1st menstrual day before the intervention
Hamilton Anxiety Scale (HAM-A)	Patients with chronic pain often experience mood disorders, such as depression and anxiety. The Hamilton Anxiety Scale (HAM-A) will be used to assess the intensity of anxiety symptoms. The scale measures both mental and physical anxiety with 14 symptom-defined items. Each item is scored from 0 (not present) to 4 (severe). The total score range is 0-56. On the anxiety scale, scores of 17 or below indicate mild anxiety, while scores of 18-24 indicate moderate anxiety, and scores of 25-30 indicate severe anxiety.	Immediately after the intervention
6-Minute Walk Test (6MWT)	The 6-Minute Walk Test (6MWT) will evaluate submaximal functional capacity. 6MWT measures the maximum distance participants can walk as quickly as possible for 6 minutes.	On the 1st menstrual day before the intervention
6-Minute Walk Test (6MWT)	The 6-Minute Walk Test (6MWT) will evaluate submaximal functional capacity. 6MWT measures the maximum distance participants can walk as quickly as possible for 6 minutes.	Immediately after the intervention
Positive and Negative Affect Schedule (PANAS)	For taVNS administration, the positive and negative affect will be assessed before and after treatment using the Positive and Negative Affect Schedule (PANAS). This 5-point Likert-type scale was developed in 1988 and includes 20 items: 10 positive and 10 negative. A score range of 10-50 assesses both positive and negative effects.	On the 1st menstrual day before the intervention
Positive and Negative Affect Schedule (PANAS)	For taVNS administration, the positive and negative affect will be assessed before and after treatment using the Positive and Negative Affect Schedule (PANAS). This 5-point Likert-type scale was developed in 1988 and includes 20 items: 10 positive and 10 negative. A score range of 10-50 assesses both positive and negative effects.	Immediately after the intervention

Collaborators and Investigators

• Sponsor: Artvin Coruh University
• Investigators: Principal Investigator: Zeynep Yıldız Kızkın, Lecturer, Artvin Çoruh University

Publications and helpful links

General Publications

• Habibi N, Huang MS, Gan WY, Zulida R, Safavi SM. Prevalence of Primary Dysmenorrhea and Factors Associated with Its Intensity Among Undergraduate Students: A Cross-Sectional Study. Pain Manag Nurs. 2015 Dec;16(6):855-61. doi: 10.1016/j.pmn.2015.07.001. Epub 2015 Aug 29.
• Kane RL, Bershadsky B, Rockwood T, Saleh K, Islam NC. Visual Analog Scale pain reporting was standardized. J Clin Epidemiol. 2005 Jun;58(6):618-23. doi: 10.1016/j.jclinepi.2004.11.017.
• Ju H, Jones M, Mishra G. The prevalence and risk factors of dysmenorrhea. Epidemiol Rev. 2014;36:104-13. doi: 10.1093/epirev/mxt009. Epub 2013 Nov 26.
• Karout S, Soubra L, Rahme D, Karout L, Khojah HMJ, Itani R. Prevalence, risk factors, and management practices of primary dysmenorrhea among young females. BMC Womens Health. 2021 Nov 8;21(1):392. doi: 10.1186/s12905-021-01532-w.
• Burnett M, Lemyre M. No. 345-Primary Dysmenorrhea Consensus Guideline. J Obstet Gynaecol Can. 2017 Jul;39(7):585-595. doi: 10.1016/j.jogc.2016.12.023.
• Itani R, Soubra L, Karout S, Rahme D, Karout L, Khojah HMJ. Primary Dysmenorrhea: Pathophysiology, Diagnosis, and Treatment Updates. Korean J Fam Med. 2022 Mar;43(2):101-108. doi: 10.4082/kjfm.21.0103. Epub 2022 Mar 17.
• Wang L, Wang Y, Wang Y, Wang F, Zhang J, Li S, Wu M, Li L, Rong P. Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Expert Rev Med Devices. 2022 Jan;19(1):43-61. doi: 10.1080/17434440.2022.2020095. Epub 2022 Jan 13.
• Wang YJ, Hsu CC, Yeh ML, Lin JG. Auricular acupressure to improve menstrual pain and menstrual distress and heart rate variability for primary dysmenorrhea in youth with stress. Evid Based Complement Alternat Med. 2013;2013:138537. doi: 10.1155/2013/138537. Epub 2013 Dec 12.
• Pegado R, Silva LK, da Silva Dantas H, Andrade Camara H, Andrade Mescouto K, Silva-Filho EM, Lopes JM, Micussi MTABC, Correia GN. Effects of Transcranial Direct Current Stimulation for Treatment of Primary Dysmenorrhea: Preliminary Results of a Randomized Sham-Controlled Trial. Pain Med. 2020 Dec 25;21(12):3615-3623. doi: 10.1093/pm/pnz202.
• Dutra LRDV, Pegado R, Silva LK, da Silva Dantas H, Camara HA, Silva-Filho EM, Correia GN, Micussi MTABC. Modulating Anxiety and Functional Capacity with Anodal tDCS Over the Left Dorsolateral Prefrontal Cortex in Primary Dysmenorrhea. Int J Womens Health. 2020 Apr 5;12:243-251. doi: 10.2147/IJWH.S226501. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2023
• Primary Completion (Actual): January 15, 2024
• Study Completion (Actual): January 30, 2024

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: November 22, 2023
• First Posted (Actual): November 24, 2023

Study Record Updates

• Last Update Posted (Actual): October 29, 2024
• Last Update Submitted That Met QC Criteria: October 28, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Pain; Dysmenorrhea; Function; Menstrual cycle
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathologic Processes; Pelvic Pain; Menstruation Disturbances; Dysmenorrhea
• Other Study ID Numbers: Vagus Nerve Stimulation

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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