Autonomic Nervous System ModulationNCT05922059
Effects of Autonomic Nervous System Modulation on Heart Rate Variability and Musculoskeletal Manifestations in Patients With Chronic Neck Pain
A study testing Transcutaneous vagus nerve stimulation, Heart rate variability biofeedback and Standard-care physiotherapy in people with Autonomic Nervous System Modulation, run by Imam Abdulrahman Bin Faisal University.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autonomic Nervous System Modulation
- What is being tested?
- Transcutaneous vagus nerve stimulation, Heart rate variability biofeedback and Standard-care physiotherapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- No sites listed yet
- Study dates
- 18 Jul 2023to 31 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
No sites are listed yet.
About this study
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.
Read the 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.
- Conditions
- Autonomic Nervous System Modulation
- Being tested
- Transcutaneous vagus nerve stimulation, Heart rate variability biofeedback, Standard-care physiotherapy
- Keywords
- Vagus nerve stimulation, Neck pain, Heart rate variability, Heart rhythm coherence feedback
- Medical subject headings
- Neck Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous vagus nerve stimulationDevice
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.
Heart rate variability biofeedbackDevice
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
Standard-care physiotherapyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Vagus nerve stimulation | Experimental | Transcutaneous vagus nerve stimulation in addition to standard-care physiotherapy Receives: Device: Transcutaneous vagus nerve stimulation |
| Heart rate variability biofeedback | Experimental | Heart rate variability biofeedback in addition to standard-care physiotherapy Receives: Device: Heart rate variability biofeedback |
| standard-care physiotherapy alone | Active comparator | standard-care physiotherapy Receives: Other: Standard-care physiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Change from baseline VAS after 6 weeks
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Change from baseline NDI after 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2023
- Study start18 Jul 2023 (estimated)
- Primary completion30 Oct 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autonomic Nervous System ModulationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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).
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 102 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imam Abdulrahman Bin Faisal University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hani Alkhawajah, Imam Abdulrahman Bin Faisal University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05922059
- Sponsor's protocol ID
- IRB-PGS-2023-03-096
- Status last verified
- Jul 2023
- First submitted
- 8 Jun 2023
- Last updated
- 19 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The work will be published in peer review journal
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Autonomic Nervous System Modulation on Heart Rate Variability and Musculoskeletal Manifestations in Patients With Chronic Neck Pain
- ClinicalTrials.gov ID
- NCT05922059
- Acronym / sponsor ID
- IRB-PGS-2023-03-096
- Conditions
- Autonomic Nervous System Modulation
- Keywords
- Vagus nerve stimulation, Neck pain, Heart rate variability, Heart rhythm coherence feedback
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 102 participants (estimated)
- Lead sponsor
- Imam Abdulrahman Bin Faisal UniversityUniversity, hospital or other
- Study start
- 18 Jul 2023 (estimated)
- Primary completion
- 30 Oct 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 28 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
- 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).
| Arm | Type | Receives |
|---|---|---|
| Vagus nerve stimulation | Experimental | Device: Transcutaneous vagus nerve stimulationTranscutaneous vagus nerve stimulation in addition to standard-care physiotherapy |
| Heart rate variability biofeedback | Experimental | Device: Heart rate variability biofeedbackHeart rate variability biofeedback in addition to standard-care physiotherapy |
| standard-care physiotherapy alone | Active comparator | Other: Standard-care physiotherapystandard-care physiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous vagus nerve stimulationAuricular 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. | Device | Vagus nerve stimulation |
| Heart rate variability biofeedbackThe 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 | Device | Heart rate variability biofeedback |
| Standard-care physiotherapyconsists 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. | Other | standard-care physiotherapy alone |
Primary outcome
Heart-rate variability (HRV)
Time frame: Baseline
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
Heart-rate variability (HRV)
Time frame: Change from baseline HRV after 3 weeks
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
Heart-rate variability (HRV)
Time frame: Change from baseline HRV after 6 weeks
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
Visual analog scale (VAS)
Time frame: Baseline
Current pain intensity will be measured using a 10-cm VAS with endpoints marked 'no pain' at 0 and 'worst pain imaginable at 10.
Visual analog scale (VAS)
Time frame: Change from baseline VAS after 3 weeks
Current pain intensity will be measured using a 10-cm VAS with endpoints marked 'no pain' at 0 and 'worst pain imaginable at 10.
Visual analog scale (VAS)
Time frame: Change from baseline VAS after 6 weeks
Current pain intensity will be measured using a 10-cm VAS with endpoints marked 'no pain' at 0 and 'worst pain imaginable at 10.
6 secondary outcomes
Pressure pain threshold (PPT)
Time frame: Baseline
Pressure pain threshold (PPT)
Time frame: Change from baseline PPT after 3 weeks
Pressure pain threshold (PPT)
Time frame: Change from baseline PPT after 6 weeks
Neck Disability Index (NDI)
Time frame: Baseline
Neck Disability Index (NDI)
Time frame: Change from baseline NDI after 3 weeks
Neck Disability Index (NDI)
Time frame: Change from baseline NDI after 6 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2023.
- Individual participant dataSharing planned: Yes. The work will be published in peer review journal
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous vagus nerve stimulation, Heart rate variability biofeedback and Standard-care physiotherapy in people with Autonomic Nervous System Modulation, run by Imam Abdulrahman Bin Faisal University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hani A Alkhawajah, MSc (0138966666 ext. 1074, hkhawajah@iau.edu.sa), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart-rate variability (HRV) (time frame: Baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2023.