Clinical trial NCT05922059: Effects of Autonomic Nervous System Modulation on Heart Rate Variability and Musculoskeletal Manifestations in Patients With Chronic Neck Pain
Official title: Effects of Autonomic Nervous System Modulation on Heart Rate Variability and Musculoskeletal Manifestations in Patients With Chronic Neck Pain
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Autonomic Nervous System Modulation
Keywords: Vagus nerve stimulation
Neck pain
Heart rate variability
Heart rhythm coherence feedback
Lead sponsor: Imam Abdulrahman Bin Faisal University
Sponsor class: OTHER
First posted: 2023-06-28
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Group A (transcutaneous vagus nerve stimulation + standard-care physiotherapy), Group B (HRV-BF + standard-care physiotherapy), or Group C (standard-care physiotherapy alone).
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Heart-rate variability (HRV)
timeFrame: Baseline
measure: Heart-rate variability (HRV)
timeFrame: Change from baseline HRV after 3 weeks
measure: Heart-rate variability (HRV)
timeFrame: Change from baseline HRV after 6 weeks
measure: Visual analog scale (VAS)
timeFrame: Baseline
measure: Visual analog scale (VAS)
timeFrame: Change from baseline VAS after 3 weeks
measure: Visual analog scale (VAS)
timeFrame: Change from baseline VAS after 6 weeks
Secondary outcomes:
measure: Pressure pain threshold (PPT)
timeFrame: Baseline
measure: Pressure pain threshold (PPT)
timeFrame: Change from baseline PPT after 3 weeks
measure: Pressure pain threshold (PPT)
timeFrame: Change from baseline PPT after 6 weeks
measure: Neck Disability Index (NDI)
timeFrame: Baseline
measure: Neck Disability Index (NDI)
timeFrame: Change from baseline NDI after 3 weeks
measure: Neck Disability Index (NDI)
timeFrame: Change from baseline NDI after 6 weeks
Other outcomes:
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