Effects of Autonomic Nervous System Modulation on Heart Rate Variability and Musculoskeletal Manifestations in Patients With Chronic Neck Pain

Background: Chronic neck pain is a widespread musculoskeletal disorder. Studies investigating the effect of autonomic nervous system (ANS) modulation in chronic neck pain are scarce. This study aims to examine the effects of ANS modulation on heart rate variability, pain, and function in patients with chronic neck pain. Methods: The intended study is a double-blind, randomized controlled trial in a parallel three arms fashion. Hundred and two patients with chronic neck pain will be recruited from King Fahd Hospital of the University in Alkhobar, Saudi Arabia. The patients will be randomly allocated equally into one of three groups. Group A (n = 34) will receive transcutaneous vagus nerve stimulation (tVNS) and standard-care physiotherapy (SC-PT). Group B (n = 34) will receive heart rate variability biofeedback (HRV-BF) and SC-PT. Group C (n = 34) will receive SC-PT alone. Each group will receive the intervention three times per week for six weeks. The primary outcome measures are HRV to assess ANS and the visual analog scale for pain intensity. The secondary outcome measures are pressure pain threshold and neck disability index. All these measures will be assessed on three occasions; at baseline, after three weeks, and after six weeks from baseline. For the statistical analysis, normality of the data will be performed prior to the analyses and suitable statistical tests will be applied to examine the effect of the interventions between the groups. The significance level sets at P < 0.05.

Study Overview

• Status: Not yet recruiting
• Conditions: Autonomic Nervous System Modulation
• Intervention / Treatment: Device: Transcutaneous vagus nerve stimulation; Device: Heart rate variability biofeedback; Other: Standard-care physiotherapy

Detailed Description

Sample size calculation was performed using statistical software (G*Power 3.1). The effect size (ES) of HRV was obtained from a previous study (Hallman et al., 2011). The following combination was used to calculate the sample size: analysis of variance (ANOVA), repeated measures, within-between interaction, ES of 0.15, an alpha level of 0.05, power (1-β) of 80%, correlation among repeated measure of 0.5, with three groups and three measurements (time points) and non-sphericity correction (Є) of 1. The estimated desired sample size was 93 patients. Three patients per group will be needed considering a 10% attrition rate. Thus, the total required sample size is 102 patients, 34 patients in each group.

The study will be conducted in the Department of Physiotherapy at KFHU Saudi Arabia. Patients with chronic neck pain who will attend KFHU and fit the inclusion criteria will be recruited consecutively and randomly allocated into Group A (transcutaneous vagus nerve stimulation + standard-care physiotherapy), Group B (HRV-BF + standard-care physiotherapy), or Group C (standard-care physiotherapy alone). The randomization sequence will be computer-generated using the GraphPad website (http://www.graphpad.com/). Hundred and two patients will be uniquely randomized equally into three different groups; each number and its allocated group will be written on a piece of paper and concealed in an opaque envelope. A receptionist will inform the treating therapist about the patient's allocation later after the baseline measurements are performed.

An independent, a physiotherapist (assessor) from the Department of Physiotherapy (with > 10 years of clinical experience in physiotherapy) who is blinded to the allocation (treatment group) of the patients will collect the demographic data and baseline outcome measurements. Then, the assessor will leave the room to remain blind to conditions. At the same time, the treating physiotherapist, the main researcher, (with > 10 years of clinical experience in musculoskeletal physiotherapy) will apply the treatment protocol according to the patient's allocated group. The treating therapist will be blind to the outcome measurements until the patients end their role in the study. Patients will be asked not to discuss their treatment experience with the assessor. The assessor will perform the outcome measurements three weeks and six weeks after intervention.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hani A Alkhawajah, MSc; Phone Number: 1074 0138966666; Email: hkhawajah@iau.edu.sa

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• adult aged ≥ 18 years old
• have had neck pain for three months or more
• reported peak neck pain of more than three on visual analogue scale (VAS) over the previous 24 hours

Exclusion Criteria:

• have had neck surgery
• intra-articular corticosteroid injection within six months
• current or past (within four weeks) oral corticosteroid use
• neurological conditions
• altered sensation to pressure
• pregnancy
• exhibited cognitive difficulties
• arm numbness or tingling
• cardiac pacemaker or other implantable stimulators
• cardiac arrhythmia
• history of myocardial infarction
• local auricular diseases
• symptomatic orthostatic hypotension

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vagus nerve stimulation; Transcutaneous vagus nerve stimulation in addition to standard-care physiotherapy	Device: Transcutaneous vagus nerve stimulation; Auricular transcutaneous vagus nerve stimulation will be used in the left cavity of the external ear with a stimulation frequency of 20-30 Hz for half hour. Monophasic rectangular waveforms will be used, and the intensity will be adjusted below the patient's pain threshold.
Experimental: Heart rate variability biofeedback; Heart rate variability biofeedback in addition to standard-care physiotherapy	Device: Heart rate variability biofeedback; The patient will receive visual HRV feedback during resonance frequency breathing. Finally, the patient will be instructed to maximize their peak-to-peak HRV and attain the phase between respiration and HRV changes as closely as possible
Active Comparator: standard-care physiotherapy alone; standard-care physiotherapy	Other: Standard-care physiotherapy; consists of cervical mobilization on the painful segment, isometric exercise for neck flexors, and a combination of strengthening and stretching exercises from sitting position; cervical extensors strengthening exercise using red color Thera-band and stretching exercises upper trapezius of the painful side.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart-rate variability (HRV)	the changes in the inter-beat intervals (IBIs) that will be used to quantify the amount of HRV observed during monitoring periods (<1 min to >24 h). In this study, the monitoring period will be five minutes	Baseline
Heart-rate variability (HRV)	the changes in the inter-beat intervals (IBIs) that will be used to quantify the amount of HRV observed during monitoring periods (<1 min to >24 h). In this study, the monitoring period will be five minutes	Change from baseline HRV after 3 weeks
Heart-rate variability (HRV)	the changes in the inter-beat intervals (IBIs) that will be used to quantify the amount of HRV observed during monitoring periods (<1 min to >24 h). In this study, the monitoring period will be five minutes	Change from baseline HRV after 6 weeks
Visual analog scale (VAS)	Current pain intensity will be measured using a 10-cm VAS with endpoints marked 'no pain' at 0 and 'worst pain imaginable at 10.	Baseline
Visual analog scale (VAS)	Current pain intensity will be measured using a 10-cm VAS with endpoints marked 'no pain' at 0 and 'worst pain imaginable at 10.	Change from baseline VAS after 3 weeks
Visual analog scale (VAS)	Current pain intensity will be measured using a 10-cm VAS with endpoints marked 'no pain' at 0 and 'worst pain imaginable at 10.	Change from baseline VAS after 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure pain threshold (PPT)	A digital pressure algometer (Somedic AB, Farsta, Sweden) with a surface probe of 1 cm2 and a rate of 40 kPa/s will be used to quantify the pain intensity. The measurement will be taken on the painful area. Participants will be instructed to activate a button when the sensation of pressure becomes painful, and the resultant value will be recorded. Three measurements will be performed. The average value will be recorded for analysis.	Baseline
Pressure pain threshold (PPT)	A digital pressure algometer (Somedic AB, Farsta, Sweden) with a surface probe of 1 cm2 and a rate of 40 kPa/s will be used to quantify the pain intensity. The measurement will be taken on the painful area. Participants will be instructed to activate a button when the sensation of pressure becomes painful, and the resultant value will be recorded. Three measurements will be performed. The average value will be recorded for analysis.	Change from baseline PPT after 3 weeks
Pressure pain threshold (PPT)	A digital pressure algometer (Somedic AB, Farsta, Sweden) with a surface probe of 1 cm2 and a rate of 40 kPa/s will be used to quantify the pain intensity. The measurement will be taken on the painful area. Participants will be instructed to activate a button when the sensation of pressure becomes painful, and the resultant value will be recorded. Three measurements will be performed. The average value will be recorded for analysis.	Change from baseline PPT after 6 weeks
Neck Disability Index (NDI)	The NDI is a self-assessment questionnaire for the specific functional status of individuals with neck pain. It consists of ten sections: pain, personal care, weight gain, reading, headache, concentration, work, driving, sleeping, and leisure. Each section is scaled from 0 to 5, where 0 represents "painless" and 5 represents "the worst pain imaginable." The points obtained are added to a total score.	Baseline
Neck Disability Index (NDI)	The NDI is a self-assessment questionnaire for the specific functional status of individuals with neck pain. It consists of ten sections: pain, personal care, weight gain, reading, headache, concentration, work, driving, sleeping, and leisure. Each section is scaled from 0 to 5, where 0 represents "painless" and 5 represents "the worst pain imaginable." The points obtained are added to a total score.	Change from baseline NDI after 3 weeks
Neck Disability Index (NDI)	The NDI is a self-assessment questionnaire for the specific functional status of individuals with neck pain. It consists of ten sections: pain, personal care, weight gain, reading, headache, concentration, work, driving, sleeping, and leisure. Each section is scaled from 0 to 5, where 0 represents "painless" and 5 represents "the worst pain imaginable." The points obtained are added to a total score.	Change from baseline NDI after 6 weeks

Collaborators and Investigators

• Sponsor: Imam Abdulrahman Bin Faisal University

Study record dates

Study Major Dates

• Study Start (Estimated): July 18, 2023
• Primary Completion (Estimated): October 30, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: June 8, 2023
• First Submitted That Met QC Criteria: June 18, 2023
• First Posted (Actual): June 28, 2023

Study Record Updates

• Last Update Posted (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: July 18, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Vagus nerve stimulation; Neck pain; Heart rate variability; Heart rhythm coherence feedback
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Neck Pain
• Other Study ID Numbers: IRB-PGS-2023-03-096

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The work will be published in peer review journal
• IPD Sharing Time Frame: When data collection finalized. A manuscript will be written for publication. The estimated time is 1 year. After publication in peer review journal, the data will remain in the journal in accordance to journal policy
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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