The study aims to estimate treatment effects in a balanced placebo design (BPD) to specify to which extent contextual factors interact in preventive migraine treatment and influence adverse event occurrence in patients with chronic migraine. Using a clinical within-subjects design, patients with chronic migraine will receive four treatment conditions in a randomized order.
The existing paradigm for testing the effect of treatment is the double-blind 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 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Standard dose of Fremanezumab, 225 mg (Ajovy) injected subcutaneously
Inactive placebo (saline) injected subcutaneously in the same volume as the active drug
Department of Psychology and Behavioral sciences, Aarhus BSS, Aarhus University
Aarhus C, Denmark, Denmark
RECRUITINGDepartment of Clinical Medicine, Aarhus University Hospital
Aarhus N, Denmark, Denmark
RECRUITINGModerate/severe headache days
Total number of moderate/severe headache days will be measured 28 days before and after each treatment administration. Headache days will be recorded by the presence of headache (yes/no), peak pain intensity (mild/moderate/severe), and duration (\< 4h or ≥ 4h), acute medication intake type (triptan/ergotamine/other) and migraine associated symptoms.
Time frame: Through study completion, an average of 8 months
Headache/pain intensity
Headache/pain intensity rated on a 11-point Numerical Rating Scale (0=no pain; 10=worst pain intensity) will also be measured 28 days before and after each treatment administration.
Time frame: 8 months
Adverse events
Occurrence of adverse events in each treatment condition recorded by the presence of adverse events ascribed to the treatment, measured by free recall and by prompting.
Time frame: 24 hours, 14 and 28 days after each treatment administration
Migraine days
Total number of migraine days will be measured 28 days before and after each treatment condition.
Time frame: Through study completion, an average of 8 months
Intensity of migraine
A categorical, four-point rating scale will be used to rate each migraine day as absent, mild, moderate, or severe. It is is graded mild when it does not inhibit work or other activities, moderate when it inhibits but does not prohibit work or other activities, and severe when it prohibits work and other activities.
Time frame: Through study completion, an average of 8 months
Acute treatment utilization
The use of acute migraine medication will be recorded, including the number of days and the specific drug used.
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Enrollment
60
Time frame: Through study completion, an average of 8 months
Positive and negative affect (PANAS)
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).
Time frame: Pre-treatment and 28 days after each treatment administration
Hospital Anxiety and Depression Scale (HADS)
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.
Time frame: Pre-treatment and 28 days after each treatment administration
Quality of life (SF-12)
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.
Time frame: Pre-treatment and 28 days after each treatment administration
HIT-6
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).
Time frame: Pre-treatment and 28 days after each treatment administration
Intensity of experienced adverse events
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)
Time frame: 24 hours, 14 days and 28 days after each treatment administration