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

Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06146569
• Other study ID #: Vagus Nerve Stimulation
• Status: Enrolling by invitation
• Phase: N/A
• Start date: November 15, 2023
• Est. completion date: January 30, 2024

Study information

• Verified date: November 2023
• Source: Artvin Coruh University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 34
• Est. completion date: January 30, 2024
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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).

Related Conditions & MeSH terms

• Dysmenorrhea
• Dysmenorrhea Primary
• Pain

Intervention

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 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.

Locations

Country	Name	City	State
Turkey	Zeynep Yildiz Kizkin	Artvin

Sponsors (1)

Lead Sponsor	Collaborator
Artvin Coruh University

Country where clinical trial is conducted

Turkey, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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