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Specific Neck Rehabilitation for Unilateral Headache and Neck Pain, and Structural and Functional Changes in the Brain

Primary Purpose

Cervicogenic Headache

Status
Active
Phase
Not Applicable
Locations
Norway
Study Type
Interventional
Intervention
Specific neck rehabilitation
Standard primary health care
Sponsored by
University of Tromso
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cervicogenic Headache focused on measuring unilateral headache, cervical pain, neck pain, rehabilitation, structural brain changes, surface based volumetry, diffusion tensor imaging, functional brain changes, sensorimotor control, craniocervical flexion, vestibular rehabilitation, cortical thickness

Eligibility Criteria

25 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Unilateral headache and neck pain for 2 years or more
  • Minimum one headache attack pr week (numeric rating scale ≥4)
  • Five or more of Antonaci's seven diagnostic criteria
  • Neck Disability Index score ≥8 Points (≥16 percent points).

For healthy controls:

• Same age distribution

Exclusion Criteria:

  • Progressive diseases (rheumatoid arthritis, cancer)
  • Ongoing cervical infection
  • Neurological disease (syringomyelia, radiculopathy, multiple sclerosis, Parkinson's disease, ischemic stroke )
  • Other headache (>1 tension type headache or migraine attack every month)
  • Other pain conditions (including primary temporomandibular disorder and generalized pain (fibromyalgia with pain intensity >6 to digital palpation)
  • Previous or ongoing drug abuse
  • Serious psychiatric disorder.
  • Hopkins Symptom Checklist-25 score for depressive symptoms > 2.2
  • Ongoing litigation process
  • Intolerance to MRI
  • Pregnancy and lactation
  • For the subsample undergoing MR analyses: Other systemic diseases (Hypertension, hyperlipidemia, diabetes mellitus, heart disease, cerebrovascular, epilepsy or other vascular diseases) and dysmenorrhea requiring analgesics

For healthy controls:

  • Exclusion criteria as above
  • Chronic pain
  • Chronic dizziness
  • Intolerance to MRI
  • Pregnancy and lactation

Sites / Locations

  • University Hospital of North Norway

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Specific neck rehabilitation

Standard primary health care

Arm Description

The intervention includes specific neck rehabilitation as described by Jull and Falla over a period of 4 weeks and recommendations for further training.

This represents individualized therapy administered by the primary physician.

Outcomes

Primary Outcome Measures

Difference of days with headache pr week after specific neck rehabilitation vs standard primary health care
Between group comparison with a numeric variable (scale 0-7)
Differences in grey matter volume of the brain and brain stem between patients with unilateral headache and neck pain vs. healthy controls
Two independent group comparison based on volumetric analysis of cerebral grey matter also including surface based measurements (continuous variable)
Differences in cortical thickness between patients with unilateral headache and neck pain vs. healthy controls
Two independent group comparison based on surface based analyses of cerebral grey matter carried out with FreeSurfer version 6.0

Secondary Outcome Measures

Difference in pain intensity after specific neck rehabilitation vs. standard primary health care
Between group comparison with a numeric variable (scale 0-10)
Improved neck function after specific neck rehabilitation vs. standard primary health care
Between group comparison with a numeric variable (scale 0-50)
Change in grey matter volume of the brain and brain stem in patients with unilateral headache and neck pain after specific neck rehabilitation
Within group comparison based on volumetric analysis of cerebral grey matter also including surface based measurements (continuous variable)
Change in cortical thickness of the brain between patients with unilateral headache and neck pain after specific neck rehabilitation
Within group comparison based on surface based volumetric analysis of cerebral grey matter (continous variable)
Differences in white matter integrity in patients with unilateral headache and neck pain vs. healthy controls
Two independent group comparison based on diffusion tensor imaging with tract based spatial statistics analyses
Difference in white matter integrity after specific neck rehabilitation vs standard primary health care
Between group comparison based on diffusion tensor imaging with tract based spatial statistics analyses
How four week baseline headache intensity reported by a numeric rating scale is associated with regional grey matter volumes measured by surface based volumetry in patients with unilateral headache and neck pain.
Linear regression analysis will be performed where the surface based volumetric measure of cerebral grey matter is the dependent variable, and four week baseline headache intensity is independent variable. Baseline headache intensity is based on daily measures during the last 4 weeks and is reported by an electronic diary and numeric rating scale where 0 is no pain and 10 is worst imaginable pain. It is thus considered a continuous measure. Age and gender are included as covariates.
How baseline perceived cognitive function predicts volumetric differences of cerebral grey matter in patients with unilateral headache and neck pain
Linear regression analysis of surface based volumetric measures of grey matter (continuous data) and scores of Everyday Memory Questionnaire (scale 0-8).
How baseline active range of neck movement predicts neck function
A logistic regression analysis on how baseline active range of neck movement (continuous data, degrees of rotation) predicts a 30% reduction in Neck Disability Index Score (0-50). Co-factors are age, gender, education, sick-leave.
How baseline active range of neck movement predicts headache frequency
A logistic regression analysis on how baseline active range of neck movement (continuous data, degrees of rotation) predicts a 30% reduction in headache frequency (0-7). Co-factors are age, gender, education, sick-leave.
How baseline self efficacy predicts neck function
A logistic regression analysis on how baseline General self efficacy scale score (scale 10-40) predicts a 30% reduction in Neck Disability Index Score (0-50). Co-factors are age, gender, education, sick-leave.
How baseline self efficacy predicts headache frequency
A logistic regression analysis on how baseline General self efficacy scale score (scale 10-40) predicts a 30% reduction in headache frequency (0-7). Co-factors are age, gender, education, sick-leave.
How baseline fear avoidance beliefs for physical activity predict neck function
A logistic regression analysis on how baseline fear avoidance beliefs score predict a 30% reduction in Neck Disability Index Score (0-50). Co-factors are age, gender, education, sick-leave.
How baseline fear avoidance beliefs for physical activity predict headache frequency
A logistic regression analysis on how baseline fear avoidance beliefs for physical activity score predict a 30% reduction in headache frequency (0-7). Co-factors are age, gender, education, sick-leave.
Difference in intra-network connectivity of resting state networks in patients with unilateral headache and neck pain vs. healthy controls.
Two independent comparison based on baseline rs-fMRI data to compare patients and controls. In multivariate general linear models, the investigators will use DMN and other major cerebral networks, identified by independent component analysis (ICA), as dependent variables and test whether there are differences in cerebral connectivity between patients and controls. All rs-fMRI analyses will be performed with the GIFT software http://mialab.mrn.org/software/gift/index.html. An ICA procedure in GIFT will be used to identify functional networks. GIFT that has a MatLab based statistical module for general linear modelling (GLM) of rs-fMRI data that will be used for all rs-fMRI analyses.
Change of resting state connectivity in patients who report reduction in headache attacks.
Within group comparison of resting state networks between baseline and 6 months follow up in a repeated measure GLM in the GIFT. Connectivity of DMN and other major networks is dependent variable and change in number of headache attacks main predictor variable.
Changes of resting state connectivity related to pain relief after specific neck rehabilitation.
Within group comparison of resting state networks between baseline and 6 months follow up in a multivariate GLM. Change of connectiviy in DMN and other major networks is dependent variables and pain reports main covariate.
Changes in connectivity of resting state networks related to improved craniocervical flexion endurance capacity after specific neck rehabilitation.
Within group comparison of resting state networks between baseline and 6 months follow in a multivariate GLM. Connectivity of DMN and other major networks is dependent variables and craniocervical flexion endurance capacity main covariate.

Full Information

First Posted
January 14, 2016
Last Updated
May 10, 2023
Sponsor
University of Tromso
Collaborators
The Royal Norwegian Ministry of Health
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1. Study Identification

Unique Protocol Identification Number
NCT02908984
Brief Title
Specific Neck Rehabilitation for Unilateral Headache and Neck Pain, and Structural and Functional Changes in the Brain
Official Title
Effects of Specific Neck Rehabilitation on Patients With Unilateral Headache and Neck Pain (Cervicogenic Headache), and Relation to Structural and Functional Changes in the Brain
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 2016 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Tromso
Collaborators
The Royal Norwegian Ministry of Health

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
In part 1 of the project clinical effect of specific neck rehabilitation for unilateral headache and neck pain (also termed cervicogenic headache) will be compared with standard primary health care. The researchers will further study whether fear avoidance beliefs and self-efficacy predict long term neck function and headache frequency superior to active range of neck movement. Part 2 will investigate whether patients with cervicogenic headache have structural changes in cerebral grey and white matter and in connectivity of the resting state state network, and whether these are reversed after effective neck rehabilitation and correlate to symptom severity and degree of disability.
Detailed Description
The project includes two parts: Part 1: With a longitudinal semicross-over, randomized control design the investigators will compare the clinical efficacy of a 6 month specific neck rehabilitation with standard primary health care on patients with unilateral headache and neck pain ( also termed cervicogenic headache) and study whether self-efficacy and fear avoidance beliefs predict 12 month self-reported neck function and headache frequency superior to the active range of neck movement The patients will either receive a specific neck rehabilitation program or 6 month standard primary health care before they cross over to neck rehabilitation. Sociodemographic and clinical characteristics will be collected before each treatment session and 6 and 12 months later. Part 2: With a non-randomized comparative design including a subsample of the patients (n: 36) and healthy controls (n: 36) the investigators will explore whether there are structural changes in the cerebral grey and white matter, and whether cerebral connectivity within the default mode network (DMN and other major cerebral networks) are significantly different and whether the changes correlate to symptom severity and degree of disability. Structural (cortical volume and thickness) changes will measured by volumetric magnetic resonance imaging (MRi) and diffusion tensor imaging (DTI), while cerebral connectivity by resting state fMRI (rs-fMRI). Whether the anticipated cerebral changes in volume, structure and connectivity are reversed after specific neck rehabilitation will be tested by repeated measurements. Analyses of MRI scans and clinical characteristics will be performed before each treatment session and 6 months later. Statistics: Power calculations based on previous studies indicate that for the clinical part a number of 21 patients within each treatment group (a total of 42 patients) and for the MR analyses a subsample of 34 patients and 34 health controls will be sufficient to obtain a statistical power of 80% with a p-value of 5%. Due to a high drop out rate we have included a total of 57 patients. Changes between baseline and the 6 month follow up will be used for "between and within group" comparisons while 12 months data will be included for in "within-group" comparisons. Statistical predictor analyses will be performed by regression analyses. The statistician who are performing the primary end point analysis, are blinded to group assignment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervicogenic Headache
Keywords
unilateral headache, cervical pain, neck pain, rehabilitation, structural brain changes, surface based volumetry, diffusion tensor imaging, functional brain changes, sensorimotor control, craniocervical flexion, vestibular rehabilitation, cortical thickness

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Specific neck rehabilitation
Arm Type
Experimental
Arm Description
The intervention includes specific neck rehabilitation as described by Jull and Falla over a period of 4 weeks and recommendations for further training.
Arm Title
Standard primary health care
Arm Type
Active Comparator
Arm Description
This represents individualized therapy administered by the primary physician.
Intervention Type
Behavioral
Intervention Name(s)
Specific neck rehabilitation
Intervention Description
Guided craniocervical, axioscapular and proprioceptive training that includes education, postural exercises, as well as training of cervical and shoulder muscles, and vestibular rehabilitation, included oculomotor function if indicated, and general exercises
Intervention Type
Other
Intervention Name(s)
Standard primary health care
Intervention Description
The treatment may include pharmacological medication, chiropractic and physiotherapy or no active treatment
Primary Outcome Measure Information:
Title
Difference of days with headache pr week after specific neck rehabilitation vs standard primary health care
Description
Between group comparison with a numeric variable (scale 0-7)
Time Frame
6 months after baseline
Title
Differences in grey matter volume of the brain and brain stem between patients with unilateral headache and neck pain vs. healthy controls
Description
Two independent group comparison based on volumetric analysis of cerebral grey matter also including surface based measurements (continuous variable)
Time Frame
Baseline
Title
Differences in cortical thickness between patients with unilateral headache and neck pain vs. healthy controls
Description
Two independent group comparison based on surface based analyses of cerebral grey matter carried out with FreeSurfer version 6.0
Time Frame
Baseline
Secondary Outcome Measure Information:
Title
Difference in pain intensity after specific neck rehabilitation vs. standard primary health care
Description
Between group comparison with a numeric variable (scale 0-10)
Time Frame
6 months after baseline
Title
Improved neck function after specific neck rehabilitation vs. standard primary health care
Description
Between group comparison with a numeric variable (scale 0-50)
Time Frame
6 months after baseline
Title
Change in grey matter volume of the brain and brain stem in patients with unilateral headache and neck pain after specific neck rehabilitation
Description
Within group comparison based on volumetric analysis of cerebral grey matter also including surface based measurements (continuous variable)
Time Frame
6 months
Title
Change in cortical thickness of the brain between patients with unilateral headache and neck pain after specific neck rehabilitation
Description
Within group comparison based on surface based volumetric analysis of cerebral grey matter (continous variable)
Time Frame
6 months
Title
Differences in white matter integrity in patients with unilateral headache and neck pain vs. healthy controls
Description
Two independent group comparison based on diffusion tensor imaging with tract based spatial statistics analyses
Time Frame
Baseline
Title
Difference in white matter integrity after specific neck rehabilitation vs standard primary health care
Description
Between group comparison based on diffusion tensor imaging with tract based spatial statistics analyses
Time Frame
6 months after baseline
Title
How four week baseline headache intensity reported by a numeric rating scale is associated with regional grey matter volumes measured by surface based volumetry in patients with unilateral headache and neck pain.
Description
Linear regression analysis will be performed where the surface based volumetric measure of cerebral grey matter is the dependent variable, and four week baseline headache intensity is independent variable. Baseline headache intensity is based on daily measures during the last 4 weeks and is reported by an electronic diary and numeric rating scale where 0 is no pain and 10 is worst imaginable pain. It is thus considered a continuous measure. Age and gender are included as covariates.
Time Frame
Baseline
Title
How baseline perceived cognitive function predicts volumetric differences of cerebral grey matter in patients with unilateral headache and neck pain
Description
Linear regression analysis of surface based volumetric measures of grey matter (continuous data) and scores of Everyday Memory Questionnaire (scale 0-8).
Time Frame
Baseline
Title
How baseline active range of neck movement predicts neck function
Description
A logistic regression analysis on how baseline active range of neck movement (continuous data, degrees of rotation) predicts a 30% reduction in Neck Disability Index Score (0-50). Co-factors are age, gender, education, sick-leave.
Time Frame
12 months after baseline
Title
How baseline active range of neck movement predicts headache frequency
Description
A logistic regression analysis on how baseline active range of neck movement (continuous data, degrees of rotation) predicts a 30% reduction in headache frequency (0-7). Co-factors are age, gender, education, sick-leave.
Time Frame
12 months after baseline
Title
How baseline self efficacy predicts neck function
Description
A logistic regression analysis on how baseline General self efficacy scale score (scale 10-40) predicts a 30% reduction in Neck Disability Index Score (0-50). Co-factors are age, gender, education, sick-leave.
Time Frame
12 months after baseline
Title
How baseline self efficacy predicts headache frequency
Description
A logistic regression analysis on how baseline General self efficacy scale score (scale 10-40) predicts a 30% reduction in headache frequency (0-7). Co-factors are age, gender, education, sick-leave.
Time Frame
12 months after baseline
Title
How baseline fear avoidance beliefs for physical activity predict neck function
Description
A logistic regression analysis on how baseline fear avoidance beliefs score predict a 30% reduction in Neck Disability Index Score (0-50). Co-factors are age, gender, education, sick-leave.
Time Frame
12 months after baseline
Title
How baseline fear avoidance beliefs for physical activity predict headache frequency
Description
A logistic regression analysis on how baseline fear avoidance beliefs for physical activity score predict a 30% reduction in headache frequency (0-7). Co-factors are age, gender, education, sick-leave.
Time Frame
12 months after baseline
Title
Difference in intra-network connectivity of resting state networks in patients with unilateral headache and neck pain vs. healthy controls.
Description
Two independent comparison based on baseline rs-fMRI data to compare patients and controls. In multivariate general linear models, the investigators will use DMN and other major cerebral networks, identified by independent component analysis (ICA), as dependent variables and test whether there are differences in cerebral connectivity between patients and controls. All rs-fMRI analyses will be performed with the GIFT software http://mialab.mrn.org/software/gift/index.html. An ICA procedure in GIFT will be used to identify functional networks. GIFT that has a MatLab based statistical module for general linear modelling (GLM) of rs-fMRI data that will be used for all rs-fMRI analyses.
Time Frame
Baseline
Title
Change of resting state connectivity in patients who report reduction in headache attacks.
Description
Within group comparison of resting state networks between baseline and 6 months follow up in a repeated measure GLM in the GIFT. Connectivity of DMN and other major networks is dependent variable and change in number of headache attacks main predictor variable.
Time Frame
6 months after baseline
Title
Changes of resting state connectivity related to pain relief after specific neck rehabilitation.
Description
Within group comparison of resting state networks between baseline and 6 months follow up in a multivariate GLM. Change of connectiviy in DMN and other major networks is dependent variables and pain reports main covariate.
Time Frame
6 months
Title
Changes in connectivity of resting state networks related to improved craniocervical flexion endurance capacity after specific neck rehabilitation.
Description
Within group comparison of resting state networks between baseline and 6 months follow in a multivariate GLM. Connectivity of DMN and other major networks is dependent variables and craniocervical flexion endurance capacity main covariate.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Unilateral headache and neck pain for 2 years or more Minimum one headache attack pr week (numeric rating scale ≥4) Five or more of Antonaci's seven diagnostic criteria Neck Disability Index score ≥8 Points (≥16 percent points). For healthy controls: • Same age distribution Exclusion Criteria: Progressive diseases (rheumatoid arthritis, cancer) Ongoing cervical infection Neurological disease (syringomyelia, radiculopathy, multiple sclerosis, Parkinson's disease, ischemic stroke ) Other headache (>1 tension type headache or migraine attack every month) Other pain conditions (including primary temporomandibular disorder and generalized pain (fibromyalgia with pain intensity >6 to digital palpation) Previous or ongoing drug abuse Serious psychiatric disorder. Hopkins Symptom Checklist-25 score for depressive symptoms > 2.2 Ongoing litigation process Intolerance to MRI Pregnancy and lactation For the subsample undergoing MR analyses: Other systemic diseases (Hypertension, hyperlipidemia, diabetes mellitus, heart disease, cerebrovascular, epilepsy or other vascular diseases) and dysmenorrhea requiring analgesics For healthy controls: Exclusion criteria as above Chronic pain Chronic dizziness Intolerance to MRI Pregnancy and lactation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gunnvald Kvarstein, PhD
Organizational Affiliation
UiT The Arctic University of Tromsø
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of North Norway
City
Tromso
ZIP/Postal Code
9019
Country
Norway

12. IPD Sharing Statement

Plan to Share IPD
No

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Specific Neck Rehabilitation for Unilateral Headache and Neck Pain, and Structural and Functional Changes in the Brain

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