The Safety and Feasibility of tDCS Combined With Conservative Treatment for Cervicogenic Headaches

Study Overview
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Brief Summary
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Annually, up to 150,000 individuals are affected by cervicogenic headaches (CGH) in Canada with many of these cases being chronic. Current treatments for CGH are limited in efficacy and durability - indicating a dire need for novel interventions in this population. Transcranial direct current stimulation (tDCS) and physiotherapy have a high degree of safety and have been studied as interventions for many other chronic pain conditions and headache disorders. We propose to study the feasibility and safety of tDCS alongside physiotherapy for CGH further in a randomized sham controlled trial.

Detailed Description
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Annually, up to 150,000 people in Canada and experience cervicogenic headaches (CGH) with many of these patients suffering from chronic CGH. CGH is a pain disorder where pain is perceived in the head but caused by dysfunction of the cervical spine and its anatomical structure. More specifically, the pathogenesis of CGH is due to the convergence of nociceptive afferents from the upper three cervical nerves and trigeminal nerves onto second-order neurons in the trigeminocervical nucleus. The pain signaling resulting from this is also modulated through sensorineural pathways involving the thalamus and the sensorimotor cortex. As such symptoms of CGH include restricted movement, local tenderness of the upper cervical spine joints, musculoskeletal impairments, headache, local pressure hyperalgesia and bilateral thermal hypoesthesia. To date, there is no cure for chronic CGH and current treatment entails trial and error with behavior management, environmental modifications and medications. Consequently, there is a significant need for new approaches to symptom management in order to help improve functional impairment and disease burden associated with treating CGH. Transcranial direct current stimulation (tDCS) and physiotherapy have a high degree of safety and have been studied as an intervention for many other chronic pain conditions and headache disorders, including arthritis and migraines, demonstrating considerable potential. The investigators propose to study the safety and feasibility of tDCS alongside physiotherapy as a treatment for CGH in a randomized sham controlled trial. RESEARCH QUESTIONS AND OBJECTIVES The overall objective is to study the feasibility and safety of tDCS applied to the primary motor cortex in patients with CGH and to explore whether active tDCS augments the effect of rehabilitation therapy. Specifically the objectives are: Primary Objective: To determine whether active tDCS is feasible and safe compared to sham when administered with rehabilitation therapy for patients with CGH when administered 3 times per week over the course of 6 weeks; this will be measured with patient drop out rates, medication use, and adverse effects throughout the treatment process and at 6- and 12- weeks post treatment. Secondary Objective: To determine what secondary outcomes such as quality of life, headaches, pain sensitivity, neck mobility, anxiety, and depression improve with active tDCS treatment in individuals suffering with CGH. Quality of life will be measured via the European Quality of Life Five Dimension (EQ-5D), headache intensity will be measured via the Headache Intensity Test - 6 (HIT-6), headache effects on participant function will be measured via the Headache Disability Index (HDI), pain sensitivity will be measured via the Pain Sensitivity Questionnaire (PSQ), neck mobility will be measured through various motor control, strength, and endurance tests, feelings of depression will be measured via the PHQ-9 and anxiety via the GADS-7 before treatment after treatment and at 6- and 12- weeks post treatment. Third objective: To explore whether the effects of active tDCS will augment the effects of rehabilitation therapy in treating individuals with CGH. METHODS This study will be a double-blind, sham-controlled, concealed allocation, randomized, clinical trial. Clinical Assessments: Demographic information will be collected two weeks prior to starting the study including age, sex, education, headache history, concussion history, past medical history, medication use, and family medical history. Baseline questionnaires will be completed including Headache Impact Test - 6 (HIT-6), Rivermead PPCS questionnaire, Headache Disability Index (HDI), European Quality of Life Five Dimension (EQ-5D), Section A of the Quantitative Analgesics Questionnaire (QAQ-A), patient health questionnaire-9 (PHQ-9), generalized anxiety disorder scale-7 (GADS-7), Patient Reported Outcomes Measurement Information System (PROMIS), and the Pain Catastrophizing Scale (PCS). Furthermore the following baseline neck mobility assessments will be used: the Craniocervical Flexion Test (CCFT), the Cervical Extensor Endurance Test (CEET), and the Dynamometry Neck-Strength Assessment (DNSA). Patients will keep a two-week baseline headache diary before treatment, 2 weeks during treatment, 2 weeks following tDCS, and for 2 weeks before the 6 and 12 week follow up assessments (total of 8 weeks). Patients will be reassessed at the completion of their tDCS treatment, and at 6- and 12-weeks post-treatment. The assessments administered at each follow up are: Rivermead PPCS questionnaire, HIT-6, HDI, SF-12, PHQ-9, GAD-7, QAQ-A, NPRS, PSQ, CCFT, CEET, DNSA, and a tDCS Attitudes and Impressions Survey. tDCS Protocol: Patients will engage in a six-week treatment protocol with 3 sessions per week (18 treatments). This was chosen to give participants at least a day between each session in order to minimize discomfort and because the number of sessions is consistent with previous migraine literature. The primary motor cortex (M1) will be the treatment target given previous literature highlighting reduced pain sensitivity and improved motor learning outcomes following tDCS stimulation of this region. M1 will be found through measurements of the head; more specifically the point halfway between the nasion and inion as well as halfway between the left and right tragus will be found, from here we will move down 20% of the distance between the left and right tragus while staying on the line between tragi. The anode will be placed over the M1 while the cathode will be placed over the super orbital region; each electrode will be held in place with a strap and will make as much contact with the skin as possible. tDCS will be delivered via two 35cm2 surface sponge electrodes at an intensity of 2mA in the active group and 0mA in the sham group. There will be a 30 second fade in and fade out period before and after stimulation with 20 minutes of active stimulation. In the sham condition, participants will only experience the 30 second fade in period and then the stimulator will be turned off. Previous sham studies have demonstrated the efficacy of this blinding method. Physiotherapy Protocol: Participants will engage in a six-week physiotherapy program which will occur immediately following each tDCS session. The exercises to be used focus on head and back strength and motor control and were assembled by a licensed physiotherapist based on previous physiotherapy protocols for treating CGH. The exercises are performed at a level that is pain-free and are progressed when goals are reached (approximately every 2 weeks). Participants will also be expected to increase daily physical activity levels to 30 minutes per day for at least 5 days a week as a part of the physiotherapy program. This will be tracked using an exercise diary to be completed by participants each day. Statistical Analysis: Summary statistics will be done and reported so that feasibility and safety can be assessed and future studies can use the results presented for power calculations.

Official Title
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The Safety and Feasibility of Transcranial Direct Current Stimulation Combined With Conservative Treatment for Cervicogenic Headaches

Conditions
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Cervicogenic Headache

Intervention / Treatment
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* Device: Transcranial Direct Current Stimulation
* Device: Sham Transcranial Direct Current Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with cervicogenic headaches based on International Headache Society Guidelines lasting greater than 12 weeks The International Headache Society Guidelines are as follows: A) Presence of a headache fulfilling criterion C; B) Clinical and/or imaging evidence of a disorder or lesion within the cervical spine or soft tissues of the neck, known to be able to cause headache; C) Evidence of causation demonstrated by at least two of the following: (a) Headache has developed in temporal relation to the onset of the cervical disorder or appearance of the lesion; (b) Headache has significantly improved or resolved in parallel with improvement in or resolution of the cervical disorder or lesion; (c) Cervical range of motion is reduced and headache is made significantly worse by provocative maneuvers; (d) Headache is abolished following diagnostic blockade of a cervical structure or its nerve supply. Average pain score ≥ 4/10 and Neck Disability score ≥ 28/50 Exclusion Criteria: Presence of primary or mixed headaches (ie. Migraines and tension type headaches) Known spinal pathology (tumour, fracture, etc) Nerve root pain/sensory loss Muscular or joint inflammatory conditions Neurological or psychiatric conditions Undergone recent surgery (within prior year) Have contraindications to tDCS (metal or electronic implants in the brain/skull; metal or electronic implants in other sites on the body; surgical procedures involving the head or spinal cord; skin problems such as dermatitis, psoriasis or eczema; epilepsy or a previous convulsion/seizure; fainting spells or syncope; pregnancy or any chance of pregnancy; previous electrical or magnetic stimulation)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blind randomized placebo controlled clinical trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active tDCS with physiotherapy<br>Patients will engage in a six-week treatment protocol with 3 sessions per week (18 treatments). This was chosen to minimize discomfort and ensure the number of sessions is consistent with previous migraine literature. The primary motor cortex (M1) will be the treatment target to reduce pain sensitivity and improve motor learning. M1 will be found through measurements of the head: the point halfway between the nasion and inion and halfway between the left and right tragus will be found, we will then move down 20% of the inter-tragi distance and place the anode there. The cathode will then be placed over the super orbital region. Each electrode will be held in place with a strap and will make as much contact with the skin as possible. tDCS will be delivered via two 35cm2 surface sponge electrodes at an intensity of 2mA in the active group. | Device: Transcranial Direct Current Stimulation<br>* See treatment arm description<br>|
| Sham Comparator: Sham tDCS with physiotherapy<br>In the sham condition, the number of sessions, placement of electrodes, and types of electrodes used will be the same, however, only a 30 second ramp up period will be administered to emulate active tDCS therapy. Patients will be able to hear the sounds of the device and will feel slight tingling for the first 30 seconds but will receive no active stimulation. Previous sham studies have demonstrated efficacy of the blinding method. | Device: Sham Transcranial Direct Current Stimulation<br>* See sham comparator arm description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of tDCS through change in participant rate, change in pain intensity, frequency, and duration, and change in medication usage | The feasibility of tDCS will be measured through changes in participant enrolment and dropout rates. | To be assessed throughout the 6 weeks of treatment and at the 6 and 12 week follow up | 
| Safety of tDCS through change in adverse effect rates from before treatment to after. | The safety of tDCS will primarily be measured through changes in safety questionnaire scores, and medication usage. Safety questionnaires ask participants to rate commonly experienced symptoms from 0-100 (0= Not occurring, 100 = Most severe). The symptoms assessed are itchiness, tingling, burning sensations, headache, fatigue, nausea, and mood difficulties. | To be assessed throughout the 6 weeks of treatment and at the 6 and 12 week follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| European Quality of Life Five Dimension (EQ-5D) | Quality of life will be measured via the European Quality of Life Five Dimension (EQ-5D). Ranges from 0-25 with higher scores indicating reduced quality of life. | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| Headache Impact Test 6 (HIT-6) | Headache intensity will be measured via the Headache Intensity Test - 6 (HIT-6). This test ranges between a score of 36 and 78 with higher scores meaning increased headache intensity and frequency. | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| Headache Disability Index (HDI) | Headache effects on participant function will be measured via the Headache Disability Index (HDI). Scores on this index range from 0-100 with higher scores indicating more severe disability as a result of headaches. | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| Pain Catastrophizing Scale (PCS) | Pain sensitivity will be measured via the Pain Catastrophizing Scale (PCS). Scores on this scale range from 0-52 with higher scores indicating greater sensitivity to pain. | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| PROMIS Pain Interference Scale | Patient Reported Outcomes Measurement Information System (PROMIS) Pain interference scale. Ranges from 4-20 with increasing scores meaning increased pain interference in daily life. | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| Craniocervical Flexion Test (CCFT) | Fine motor control of neck muscles will be measured via the Craniocervical Flexion Test (CCFT). | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| Cervical Extensor Endurance Test (CEET) | Neck muscle endurance will be measured via the Cervical Extensor Endurance Test (CEET). | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| Dynamometry Neck-Strength Assessment (DNSA) | Neck muscle strength will be measured via the Dynamometry Neck-Strength Assessment (DNSA). | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| Patient health questionnaire 9 (PHQ-9) | Depression will be measured via the patient health questionnaire-9 (PHQ-9). Ranges from 0-27 with higher scores meaning more depressive symptoms. | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| Generalized anxiety disorder scale 7 (GADS-7) | Anxiety will be measured via the generalized anxiety disorder scale-7 (GADS-7). Ranges from 0-21 with her scores meaning more symptoms of anxiety. | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| Cervical Flexor Endurance Test (CFET) | Neck muscle endurance will be measured via the Cervical Flexor Endurance Test (CFET) as well. | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| Numeric Pain Rating Scale (NPRS) | Pain intensity will be assessed through the numeric pain rating scale (NPRS). This scale ranges from 0-10 with a higher score indicating more pain intensity. | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 
| Medication usage as measured by the quantitative analgesics questionnaire. | Measure a decline, increase or stoppage of medication throughout the study. | To be assessed at baseline, immediately after treatment and at 6 and 12 weeks post treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Physiotherapy, Transcranial Direct Current Stimulation