Clinical trial NCT02908984: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: 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
Lead sponsor: University of Tromso
Sponsor class: OTHER
Collaborators: name: The Royal Norwegian Ministry of Health
First posted: 2016-09-21
Enrollment: 57
Sex: ALL
Minimum age (years): 25
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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: A parallel design power calculations based on previous studies indicated 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%. Given a 2:1 ratio following a semi-cross over design, normal distributed data, α = 0.05, different standard deviations for each group (SD 1,38 and 1,71), and a statistical power of 0,8, a calculation indicated a sample size of 36 patients for the RCT. With a dropout rate up to 35%, 54 participants would be satisfactory.

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.

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

Primary outcomes:
measure: Difference of days with headache pr week after specific neck rehabilitation vs standard primary health care
timeFrame: 6 months after baseline
measure: Differences in grey matter volume of the brain and brain stem between patients with unilateral headache and neck pain vs. healthy controls
timeFrame: Baseline
measure: Differences in cortical thickness between patients with unilateral headache and neck pain vs. healthy controls
timeFrame: Baseline
Secondary outcomes:
measure: Difference in pain intensity after specific neck rehabilitation vs. standard primary health care
timeFrame: 6 months after baseline
measure: Improved neck function after specific neck rehabilitation vs. standard primary health care
timeFrame: 6 months after baseline
measure: Change in grey matter volume of the brain and brain stem in patients with unilateral headache and neck pain after specific neck rehabilitation
timeFrame: 6 months
measure: Change in cortical thickness of the brain between patients with unilateral headache and neck pain after specific neck rehabilitation
timeFrame: 6 months
measure: Differences in white matter integrity in patients with unilateral headache and neck pain vs. healthy controls
timeFrame: Baseline
measure: Difference in white matter integrity after specific neck rehabilitation vs standard primary health care
timeFrame: 6 months after baseline
measure: 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.
timeFrame: Baseline
measure: How baseline perceived cognitive function predicts volumetric differences of cerebral grey matter in patients with unilateral headache and neck pain
timeFrame: Baseline
measure: How baseline active range of neck movement predicts neck function
timeFrame: 12 months after baseline
measure: How baseline active range of neck movement predicts headache frequency
timeFrame: 12 months after baseline
measure: How baseline self efficacy predicts neck function
timeFrame: 12 months after baseline
measure: How baseline self efficacy predicts headache frequency
timeFrame: 12 months after baseline
measure: How baseline fear avoidance beliefs for physical activity predict neck function
timeFrame: 12 months after baseline
measure: How baseline fear avoidance beliefs for physical activity predict headache frequency
timeFrame: 12 months after baseline
measure: Difference in intra-network connectivity of resting state networks in patients with unilateral headache and neck pain vs. healthy controls.
timeFrame: Baseline
measure: Change of resting state connectivity in patients who report reduction in headache attacks.
timeFrame: 6 months after baseline
measure: Changes of resting state connectivity related to pain relief after specific neck rehabilitation.
timeFrame: 6 months
measure: Changes in connectivity of resting state networks related to improved craniocervical flexion endurance capacity after specific neck rehabilitation.
timeFrame: 6 months
Other outcomes:
Locations:
city: Tromso
country: Norway
facility: University Hospital of North Norway
Study officials:
affiliation: UiT The Arctic University of Tromsø
name: Gunnvald Kvarstein, PhD
role: PRINCIPAL_INVESTIGATOR
References: