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| Name | Class |
|---|---|
| University of Southern Denmark | OTHER |
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This randomized, single-blinded study will investigate the effects of Spinal Manipulative Therapy on Heart Rate Variability and Pain Sensitivity in a population of patients with recurrent and persistent neck pain. Alongside, the study will also develop a clinical test for Conditioned Pain Modulation and investigate its predictive properties.
Previously, Spinal Manipulative Therapy (SMT) was thought to mechanically affect the restoration of muscular and joint function, by normalising muscle tension and joint mobility. However, recent research has suggested that SMT may be influencing the incoming/ascending pain signals and/or the excitability of the central pain regulating mechanisms. People with chronic neck/shoulder pain have been found to have a disturbance of the Autonomic Nervous System (ANS). Little is known about the changes in the ANS and its relation to changes in pain in a series of treatments conducted in a clinical setting.
This multicentre randomized controlled clinical trial will be carried out in multimodal primary care clinics where both physiotherapists and chiropractors are consulted for musculoskeletal issues are selected to minimize selection bias from the patient's pre-desired treatment modality.
The subjects will be recruited among patients seeking care for persistent or recurrent Neck pain (NP), either self-selected or through referrals from general practitioners in the local areal. The aim is to study the effect of SMT and stretching exercises compared to stretching exercises alone, two well-known interventions for NP, during a two-week treatment regimen.
The primary outcome is the activity of the autonomic nervous system (Heart Rate Variability (HRV), but also Conditioned Pain Modulation (CPM) will be measured. HRV and CPM will be measured at baseline, prior to the third treatment and after the fourth treatment.
The subjective pain experience will be investigated by using two different instruments accessing pain intensity and the affective quality of pain, asked at the assessments during the two weeks of treatment and 2 months after the period of intervention ends.
Highly structured data collection procedures should provide reliable data to answer these questions. The study utilizes normal clinical procedures, which should aid the transferability of the results.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | Experimental | Stretching and Spinal Manipulative Therapy |
|
| Comparator | Active Comparator | Stretching |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stretching and Spinal manipulative therapy | Other | Subjects will be instructed to perform a series of progressively difficult stretching exercises for the neck and upper back muscles. In addition, subjects will be treated with Spinal manipulative therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Heart Rate Variability | The variation in beat-to-beat heart rate is an indicator of parasympathetic and sympathetic modulation of the heart rhythm. It is measured as the time between two R-waves on the ECG and measured in ms. | 2 weeks, the change is reported between baseline-2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Conditioned Pain Modulation, Measured as the Difference in Pain Intensity Between Two Conditions . | Conditioned Pain Modulation is assessed using a thumb clamp and a cold pressor test. Pain is rated on the Numeric Rating Scale, ranging from 10 (unbearable pain) to 0 (no pain). The outcome is the difference between these two measurements. | The test is done at baseline and again at 2 weeks, and the outcome is the difference between these two scores |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Pain Intensity | Self-reported, using the Numeric Rating Scale (0-10). High scores indicate more severe pain. The outcome is the difference between the scores measured at baseline at at two weeks. | 2 weeks, pain intensity is assessed at Baseline and after 2 weeks, the outcome is the difference between them. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Iben Axén | Karolinska Institutet | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karolinska Institutet | Stockholm | 171 77 | Sweden | |||
| Danvik Kiropraktik och Rehab |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40217263 | Derived | Galaasen Bakken A, Eklund A, Oksanen A, Axen I. The response to individualized treatment after a standardized treatment protocol among neck pain sufferers: a secondary analysis of a randomized controlled trial. Chiropr Man Therap. 2025 Apr 11;33(1):13. doi: 10.1186/s12998-025-00579-y. | |
| 36192738 | Derived | Bakken AG, Eklund A, Warnqvist A, O'Neill S, Hallman DM, Axen I. Are changes in pain associated with changes in heart rate variability in patients treated for recurrent or persistent neck pain? BMC Musculoskelet Disord. 2022 Oct 4;23(1):895. doi: 10.1186/s12891-022-05842-4. |
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Anonymized information may be shared with other researchers upon request, pending ethical approval.
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| ID | Title | Description |
|---|---|---|
| FG000 | Intervention | Stretching and Spinal Manipulative Therapy Stretching and Spinal manipulative therapy: Subjects will be instructed to perform a series of progressively difficult stretching exercises for the neck and upper back muscles. In addition, subjects will be treated with Spinal manipulative therapy |
| FG001 | Comparator | Stretching Stretching: Subjects will be instructed to perform a series of progressively difficult stretching exercises for the neck and upper back muscles. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intervention | Stretching and Spinal Manipulative Therapy Stretching and Spinal manipulative therapy: Subjects will be instructed to perform a series of progressively difficult stretching exercises for the neck and upper back muscles. In addition, subjects will be treated with Spinal manipulative therapy |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Heart Rate Variability | The variation in beat-to-beat heart rate is an indicator of parasympathetic and sympathetic modulation of the heart rhythm. It is measured as the time between two R-waves on the ECG and measured in ms. | Posted | Mean | Standard Deviation | ms | 2 weeks, the change is reported between baseline-2 weeks |
|
The participants were asked to report adverse events 1 day after the first treatment was administered.
Subjects were asked to report any adverse reactions to the first treatment through a text message, i.e. increased tenderness or fatigue in the neck, answered with an NRS-11 scale anchored by the descriptors 'No reaction' (0) and 'Worst reaction imaginable'
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intervention | Stretching and Spinal Manipulative Therapy Stretching and Spinal manipulative therapy: Subjects will be instructed to perform a series of progressively difficult stretching exercises for the neck and upper back muscles. In addition, subjects will be treated with Spinal manipulative therapy |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Minor | Musculoskeletal and connective tissue disorders | Serious /Other | Systematic Assessment | Increased pain and discomfort |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ass professor Iben Axén | Karolinska Institutet | +46704400618 | iben.axen@ki.se |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 20, 2018 | Mar 4, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D019547 | Neck Pain |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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Subjects will be randomized into two arms: 1: stretching exercises only, 2: stretching exercises and Spinal Manipulative Therapy
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The subject will not know the content of the other arm. The care provider cannot be blinded, as he/she will be performing the treatment. The investigator performing the measurements will not be aware of the treatment allocation, and the analyses will be masked for group allocation
| Stretching | Other | Subjects will be instructed to perform a series of progressively difficult stretching exercises for the neck and upper back muscles. |
|
| Change in Disability Score |
Neck Disability Index (10 questions, answer options 1-6, summary score, higher score indicating higher disabiity), reported at baseline and at 2 weeks follow up. The measure is the difference between these two scores |
| 2 weeks |
| Common Side-effects | Description and count of common side effects, data collected through a single question using text messages. Thus, the participants described their side-effects, which were categorized and counted. | 1 week |
| Stockholm |
| Sweden |
| 34844625 | Derived | Galaasen Bakken A, Eklund A, Hallman DM, Axen I. The effect of spinal manipulative therapy and home stretching exercises on heart rate variability in patients with persistent or recurrent neck pain: a randomized controlled trial. Chiropr Man Therap. 2021 Nov 29;29(1):48. doi: 10.1186/s12998-021-00406-0. |
| 34706706 | Derived | Bakken AG, Eklund A, Warnqvist A, O'Neill S, Axen I. The effect of two weeks of spinal manipulative therapy and home stretching exercises on pain and disability in patients with persistent or recurrent neck pain; a randomized controlled trial. BMC Musculoskelet Disord. 2021 Oct 27;22(1):903. doi: 10.1186/s12891-021-04772-x. |
| 31606042 | Derived | Galaasen Bakken A, Axen I, Eklund A, O'Neill S. The effect of spinal manipulative therapy on heart rate variability and pain in patients with chronic neck pain: a randomized controlled trial. Trials. 2019 Oct 12;20(1):590. doi: 10.1186/s13063-019-3678-8. |
| Comparator |
Stretching Stretching: Subjects will be instructed to perform a series of progressively difficult stretching exercises for the neck and upper back muscles. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Heart rate variability | The reported measure is the RMSSD, Root mean squared successive diferences, recorded with a sampling rate of 1000 Hz between inter-beat-intervals, measured in ms. | A few participants did not have HRV measurements of sufficient quality, and their measurements had to be excluded | Mean | Standard Deviation | ms |
|
|
|
| Secondary | Change in Conditioned Pain Modulation, Measured as the Difference in Pain Intensity Between Two Conditions . | Conditioned Pain Modulation is assessed using a thumb clamp and a cold pressor test. Pain is rated on the Numeric Rating Scale, ranging from 10 (unbearable pain) to 0 (no pain). The outcome is the difference between these two measurements. | In this analysis, the original study arms were not used, and the participants were treated as one cohort. | Posted | Mean | Standard Deviation | NRS change score | The test is done at baseline and again at 2 weeks, and the outcome is the difference between these two scores |
|
|
|
| Other Pre-specified | Change in Pain Intensity | Self-reported, using the Numeric Rating Scale (0-10). High scores indicate more severe pain. The outcome is the difference between the scores measured at baseline at at two weeks. | This is an intention-to-treat analysis. Participants are analyzed according to the arm in which they were randomized. | Posted | Mean | Standard Deviation | score on a scale | 2 weeks, pain intensity is assessed at Baseline and after 2 weeks, the outcome is the difference between them. |
|
|
|
| Other Pre-specified | Change in Disability Score | Neck Disability Index (10 questions, answer options 1-6, summary score, higher score indicating higher disabiity), reported at baseline and at 2 weeks follow up. The measure is the difference between these two scores | The disability score is based on the instrument Neck Disability Index, and the change is the difference between the last and first measurement, 2 weeks apart | Posted | Mean | Standard Deviation | score on a scale | 2 weeks |
|
|
|
| Other Pre-specified | Common Side-effects | Description and count of common side effects, data collected through a single question using text messages. Thus, the participants described their side-effects, which were categorized and counted. | Description and count of side-effects | Posted | Count of Participants | Participants | 1 week |
|
|
|
| 0 |
| 66 |
| 0 |
| 66 |
| 3 |
| 66 |
| EG001 | Comparator | Stretching Stretching: Subjects will be instructed to perform a series of progressively difficult stretching exercises for the neck and upper back muscles. | 0 | 65 | 0 | 65 | 1 | 65 |
|
The agreement stipulates that the funder has no say in the analysis, interpretation, publication or communication of the results.