Chronic Migraine, Headache, Headache Disorders, Migraine, Migraine With or Without Aura
Conditions
Keywords
Headache, Chronic migraine, Balanced placebo design, Treatment effects, Adverse events
Brief summary
The study aims to test interactions between drug and placebo-responses in acute migraine treatment and to assess variation in adverse events according to treatment information provided. Using a clinical within-subjects, balanced placebo design, patients with chronic migraine will receive four treatment conditions in a randomized order.
Detailed description
The existing paradigm for testing the effect of treatment is the double-blind randomized controlled trial (RCT) comparing an active drug to an inactive placebo. This comparison is done in order to control for contextual and psychological factors such as the patients' treatment expectations - a key factor in placebo responses. However, recent studies have indicated that some assumptions underlying the RCT may be incorrect and may lower the assay sensitivity and miscalculate the actual drug response. The so-called balanced placebo design (BPD) targets some of the shortcomings of the RCT by balancing the information given to the patients with the actual treatment administered. In this project, patients suffering from chronic migraine will receive a total of 4 injections over 8 months. Half of them are femanezumab, while the other half are placebo (an inactive injection). The injections (fremanezumab and placebo) look the same, and neither the patient nor the investigator know which injection will be administered. The order will be randomized. The injections are given with different information about what the patients are receiving. To avoid a carry-over effect, the patients will receive one injection every second month. The first month will be without treatment whereupon the patient will receive the first injection. During the first 28 days before and after each administration, patients rate outcome measures in an electronic pain/headache diary at home. In addition, they will also fill out questionnaires assessing their quality of life, psychological parameters and the headache burden.
Interventions
DRUGActive drug for chronic migraine treatment.
Standard dose of Fremanezumab, 225 mg (Ajovy) injected subcutaneously
Inactive placebo (saline) injected subcutaneously in the same volume as the active drug
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Double-blinded randomized controlled cross-over design where patients receive 1\) Fremanezumab or 2) placebo, twice.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adults (18-65 years) 2. ≥ 1-year history of migraine with or without aura according to the International Classification of Headache Disorders (ICHD-3) diagnostic criteria 3. Known chronic migraine (headache occurring ≥ 15 days per month for \> 3 months, which on at least 8 days per month has the features of migraine headache) diagnosed before age 65 4. Eligibility for preventive migraine treatment 5. Ability to speak and read Danish
Exclusion criteria
1. Use of onabotulinumtoxinA as preventive migraine treatment during the 4 months before inclusion 2. Use of other preventive migraine treatment except CGRP antagonists (However, participants are allowed to be on two stable preventive medication (antidepressant, calcium channel blockers, beta blockers or antiepileptic)- 2 months prior to inclusion until end of study), devices for migraine prevention such as transcranial magnetic stimulation and use of nerve blocks 3 months prior to inclusion 3. Use of opioid or barbiturate medications in the last four weeks before inclusion 4. Secondary headache disorders including medication overuse headache 5. Severe psychiatric, vascular disease, or known liver disease 6. Alcohol abuse or substance abuse 7. Current or planned pregnancy and lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean change in headache intensity | Measured every day during the 8 month trial period | Headache intensity rated on a 11-point Numerical Rating Scale (0=no pain; 10=worst pain intensity) measured 28 days before and after each treatment administration. |
| Mean change in moderate/severe headache days | Measured every day during the 8 month trial period | Total number of moderate/severe headache days will be measured 28 days before and after each treatment administration. Moderate/severe headache days will be recorded by the presence of headache (yes/no), peak pain intensity (mild/moderate/severe), and duration (\< 4h or ≥ 4h), as well as acute medication intake and treatment response. |
| Adverse events | 24 hours, 14 and 28 days after each treatment administration | Occurrence of adverse events in each treatment condition recorded by the presence of adverse events ascribed to the treatment, measured using free recall and prompting. For each prompted symptom, participants respond "yes" or "no" and indicate whether they believe the symptom is related to the medication, the migraine attack, or another cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Migraine days | Measured every day during the 8 month trial period | Total number of migraine days will be measured 28 days before and after each treatment condition. |
| Acute treatment utilization | Measured every day during the 8 month trial period | The use of acute migraine medication will be recorded, including the specific drug used, number of days and dose. |
| Positive and negative affect (PANAS) | Pre-treatment and 28 days after each treatment administration | PANAS will be used to measure positive and negative emotions or feelings pre- and post-treatment of each treatment condition. Positive affectivity refers to positive emotions and expressions. Negative affectivity, on the other hand, refers to negative emotions and expressions. This scale consists of words that describe different emotions and is scored on a Likert Scale ranging from 1 to 5 (1= very slightly or not at all, 2 = little, 3 = moderately, 4 = quite a bit and 5 = extremely). |
| Hospital Anxiety and Depression Scale (HADS) | Pre-treatment and 28 days after each treatment administration | It is a 14-item measure designed to assess anxiety and depression symptoms. It is rated on a 4-point Likert scale. It will be measured pre- and post-treatment of each treatment condition. |
| Quality of life (SF-12) | Pre-treatment and 28 days after each treatment administration | Short-form-12 (SF-12) is a self-reported outcome measure assessing the impact of health on an individual's everyday life. It consists of two components- physical (PCS-12) and mental (MCS-12). The summary scores are scored using norm-based scoring, where means of 50 and standard deviations of 10 are achieved. |
| HIT-6 | Pre-treatment and 28 days after each treatment administration | Headache impact test (HIT-6) measures the impact that headache has on social functioning, role functioning, vitality, cognitive functioning, and psychological distress. It consists of 6 questions. Each question can be answered with 5 responses (never, rarely, sometimes, very often, or always), which has the following numerical values (6, 8, 10, 11, and 13, respectively). |
| Intensity of experienced adverse events | 24 hours, 14 days and 28 days after each treatment administration | Intensity of the experienced adverse events will be measured on a 11-point Numerical Rating Scale (e.g., "To what extent have you been feeling fatigue/dizziness?"; 0=not at all; 10=worst imaginable) |
| Blinding | 28 days after each treatment administration and after completion of the trial | At the end of each treatment condition, participants indicate which treatment they believe to have received (fremanezumab or placebo), how certain they are on an 11-point NRS (0 = not at all certain, 10 = completely certain), and the reasons for this response (e.g., adverse events, symptom relief, characteristics of the injection, or other reasons). After completion of all four treatment conditions, participants complete a single, retrospective assessment indicating which treatment they preferred overall. Participants are also asked to briefly describe the reasons for their preference. |
Countries
Denmark
Contacts
CONTACTSigrid Juhl Lunde, MSc, PhD
PRINCIPAL_INVESTIGATORLene Vase, MSc, PhD, DMSc
Dept. of Psychology and Behavioural Sciences, Aarhus University, Aarhus, Denmark
Outcome results
None listed