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, advanced balanced placebo design, patients with episodic migraine will receive six treatment conditions in a randomized order.
The existing paradigm for testing the effect of treatments 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 study results 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 the shortcomings of the RCT by balancing the information given to the patients (correct or false) with the actual treatment administered (active treatment or placebo). In this project, the aim is to examine whether the active drug response and the placebo response interact in acute migraine treatment. Patients suffering from episodic migraine will go through six treatment conditions in randomized order. They will receive acute migraine treatment (a sumatriptan pill) or inactive treatment (a placebo pill) in the event of a developing migraine attack. Using a clinical within-subjects design, the patients receive 1) sumatriptan or 2) placebo and are told that they receive a) sumatriptan or placebo, b) sumatriptan, or c) placebo. All treatments and accompanying treatment descriptions will be administered at home.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
128
Standard dose of Sumatriptan 100 mg, which is used as an acute treatment for episodic migraine
Inactive placebo pill (100 mg) looking like the active drug
Dept. of Psychology and Behavioural Sciences
Aarhus C, Denmark
NOT_YET_RECRUITINGDepartment of Neurology, Aarhus University Hospital
Aarhus N, Denmark
RECRUITINGHeadache intensity
Headache intensity rated on a 11-point Numerical Rating Scale (("How intense is your headache right now?"; 0=no pain; 10=worst imaginable pain).
Time frame: Immediately before and 2 hours after each treatment administration
Adverse events
Occurrence of adverse events in each treatment condition recorded by the presence of adverse events ascribed to the treatment, measured using structured prompting (fatigue/drowsiness, nausea/vomiting, altered taste, feeling of warmth, flushing, feeling of cold, heaviness, muscle pain, chest pain/pressure, tingling sensations, dizziness, shortness of breath, or any other adverse event/symptom). 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.
Time frame: 2 hours after each treatment administration
Positive and negative affect (PANAS)
PANAS will be used to measure positive and negative emotions or feelings in the present moment. 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: Before and 2 hours after each treatment administration
Functional disability scale
Functional disability due to migraine will be measured on a 4-point scale (0= no disability (i.e., able to function normally); 1=mild disability (i.e., able to perform all activities of daily living but with some difficulty); 2=moderate disability (i.e., unable to perform certain activities of daily living); 3=severe disability (i.e., unable to perform most to all activities of daily living or requiring bed rest)
Time frame: 2 hours after each treatment administration
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Rescue medication
Use of rescue medication for episodic migraine (type of rescue medications, dose and time of administration) will be noted
Time frame: 2 hours after each treatment administration
Pain Freedom
Freedom from pain will be measured as yes/no.
Time frame: 2 hours after each treatment administration
Absence of the most bothersome migraine-associated symptom
Absence of the most bothersome migraine-associated symptoms such as nausea, vomiting, photophobia, and phonophobia. The participants are asked to answer the question by answering yes or no.
Time frame: 2 hours 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: 2 hours after each treatment administration
Most bothersome migraine-related symptom other than headache
Participants are asked to identify their most bothersome migraine-related symptom other than headache.
Time frame: Immediately before each treatment administration
Presence of other migraine-related symptoms
Presence of other migraine-related symptoms, including nausea, vomiting, photophobia, phonophobia, or other symptoms is assessed dichotomously (yes/no).
Time frame: 2 hours after each treatment administration
Desire for pain relief
Desire for pain relief is rated on a 11-point NRS ("How strong is your desire for pain relief from the treatment you just received?"; 0 = no desire, 10 = strongest possible desire).
Time frame: 2 hours after each treatment administration
Blinding
Participants indicate which treatment they believe to have received (sumatriptan 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 pill or envelope, or other reasons). After completion of all six treatment conditions, participants complete a single, retrospective assessment indicating which treatment they preferred overall or whether they perceived no meaningful difference between treatments. Participants are also asked to briefly describe the reasons for their preference.
Time frame: 2 hours after each treatment administration and after completion of the trial