Clinical trial NCT03671681: Mindfulness Therapy for Chronic Migraine
Official title: A Randomized Clinical Trial on the Efficacy and Cost-efficacy of Adding on a Mindfulness-based Therapy to Standard Medical Prophylaxis in the Treatment of Patients With Chronic Migraine Associated to Medication Overuse Following Structured Withdrawal: the Mind-CM Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Migraine
Medication Overuse Headache
Keywords: Chronic Migraine
Medication Overuse Headache
Mindfulness
Pharmacological Prophylaxis
Neuroimaging
Neuroinflammation
Disability
Quality of Life
Depression
Anxiety
Lead sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Sponsor class: OTHER
First posted: 2018-09-14
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim is to assess the efficacy of adding on a Mindfulness-based therapy to pharmacological prophylaxis (experimental group: pharmacological prophylaxis + Mindfulness) against pharmacological prophylaxis only (control group) on the reduction of monthly headaches frequency (primary endpoint), symptomatic medications intake, inflammatory pattern, depression, anxiety, cutaneous allodynia, improving disability and quality of life (secondary endpoints). Moreover, other aims are to assess whether adding on Mindfulness-based therapy is also associated to a superior improvement of neuroimaging pattern among patients prescribed neuromodulators or antidepressants and to assess the cost-efficacy of adding on a Mindfulness-based therapy to pharmacological prophylaxis. Mindfulness will be provided in small groups (5-7 patients each) by specifically trained therapists. The treatment consists in six 45 minutes weekly sessions in which one will work on meditation, acceptance and awareness. The program of control group will consist in education of patients, followed by pharmacological prophylaxis. Prophylaxis is prescribed based on patients' profile, such as previous failures, contraindications and so on by a neurologist with expertise in headache treatments. We expect that adding-on Mindfulness will determine a wider reduction of headaches frequency and improvement of secondary endpoints, and that disease cost reduction will support the cost-efficacy of Mindfulness. The study will be a Phase III; randomized, Open-Label; Monocentric study. Patients will be enrolled to detect a 20% difference between the two groups on the primary outcome (50% or more of headache reduction by 12 months). For each medication type and research arm 20 patients will be selected: thus 80 patients will be enrolled for neuroradiological investigation.

Detailed description: Background and significance. Chronic migraine (CM) is a negative evolution of migraine characterized by frequent headache attacks (\>45 days/three months) with a 1-year prevalence of 3.1%. Comorbidities, lifestyle and excessive intakes of symptomatic medications (medication overuse-MO) play a role in progression into CM; altered inflammatory state (WBC, peripheral blood lymphocyte subsets CD3, CD4, CD8, CD19) and dysfunctions in the mesocorticolimbic dopamine circuit were found in CMMO patients. To prevent CM-MO relapse, withdrawal of overused drugs and complementing pharmacological prophylaxis with behavioral treatments is indicated \[5\]. Withdrawal from MO and medical prophylaxis determine a 30-40% reduction in headaches frequency by 12 months, and 40-50% of patients show a reduction \>=50%. Conversely, 30% of them relapse into CM-MO by 12 months: the main drivers include overuse of analgesic compared to triptans and being on medical therapy alone compared to adjuvant psychological techniques. Research demonstrated the utility of relaxation training, stress management, cognitive-behavioral therapy in migraine disorder. Parallel to this, mindfulness showed considerable promise particularly on headache-related disability, affective distress: however, to date evidence of its efficacy is limited by small trials, short follow-up periods, inadequate power and poor consideration of primary outcomes for CM research, i.e. reduction of headaches frequency. Our main hypothesis is that mindfulness might provide additional benefit, when added to medical prophylaxis alone, on both primary (i.e. an increased number of patients showing a reduction of headaches frequency \>=50%) and secondary outcomes: reduction in the consumption of symptomatic medications (i.e. analgesics, triptans, opioids, ergot-derivate), reduction of disability, depression, anxiety and cutaneous allodynia, improvement in quality of life; reduction of costs, connected to both lower direct medical costs (e.g. drugs consumption and attendance to ER) and indirect costs (i.e. reduction in lost workdays and improved workplace efficiency); reduction in concentration of the markers of inflammatory pattern; reversible neuroadaptations highlighted by functional connectivity in regions of dopaminergic circuit.

The study will be a Phase III; randomized, Open-Label; Monocentric study. Patients will be enrolled to detect a 20% difference between the two groups on the primary outcome (50% or more of headache reduction by 12 months). We set alpha 0.05 and power 80%, and foresee that up to 12% of patients might be lost at follow-up: therefore, we determined that 170 patients should be randomized 1:1 to the two groups. Patients will be excluded if they: have psychiatric comorbidities of psychotic area; pregnancy; comorbidity with secondary headaches (e.g. idiopathic intracranial hypertension); were submitted to withdrawal from MO at least twice in the previous two years; attended any mindfulness-based therapy. For each medication type and research arm 20 patients will be selected: thus 80 patients will be enrolled for neuroradiological investigation. The treatment consists in six 45 minutes weekly sessions. The main focus of the six session will be the following: 1) introduction and meaning; 2) Focus on breath; 3) posture and body awareness; 4) meditation of sounds; 5) Guided imagery; 6) acceptance and awareness.

Our project is highly innovative as it will be the first time in which a new emerging treatment like Mindfulness is tested for its efficacy and cost-efficacy when added to standard pharmacological prophylaxis. If our hypothesis will be confirmed, then we will positively impact on: a) clinicians, that will have confirmation of another valid adjuvant treatment option; b) national health system, that will cut down the relevant costs of medication intake and indirect costs associated to reduced productivity; c) patients, that will enhance their ability to cope with headaches and improve their overall health, quality of life, work-ability and reduce their disability. Moreover, our study will address the possible impact of Mindfulness as an add-on to pharmacological prophylaxis not only on clinical data, such as headaches frequency and symptomatic medications intake, but also on biomarkers of inflammatory and functional neuroimaging patterns.

Eligibility criteria: Inclusion Criteria:

* Chronic Migraine (migraine headaches on ≥15 days of migraine headache per month, for three consecutive months) associated to Medication overuse (Regular intake for \>3 months of analgesics on \>=15 days/month or of triptans, ergotamine, NSAID, opioids or multiple drugs on \>=10 days/month). Diagnoses are made according to the third version of the International Classification of Headache Disorders (code 1.3-Chronic Migraine; code 8.2-Medication Overuse Headache).

Exclusion Criteria:

* psychiatric comorbidities of psychotic area;
* pregnancy;
* comorbidity with secondary headaches (e.g. idiopathic intracranial hypertension);
* submitted to withdrawal from MO at least twice in the previous two years;
* attended any mindfulness-based therapy

Primary outcomes:
measure: Headache frequency reduction
timeFrame: 12 months
Secondary outcomes:
measure: Neuroimaging pattern
timeFrame: 12 months
measure: Cost-efficacy
timeFrame: 3, 6, 12 months
measure: Health and disability
timeFrame: 3, 6, 12 months
measure: Disability
timeFrame: 3, 6, 12 months
measure: Change in Quality of life
timeFrame: 3, 6, 12 months
measure: Depression
timeFrame: 3, 6, 12 months
measure: Anxiety
timeFrame: 3, 6 and 12 months
measure: Allodynia
timeFrame: 3, 6 and 12 months
measure: Inflammatory pattern
timeFrame: 6 and 12 months
measure: Medications consumption
timeFrame: 3, 6 and 12 months
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico C. Besta, Neuroalgology Unit
Study officials:
References: