Headache, Migraine, Migraine With Aura, Migraine Without Aura
Conditions
Keywords
Headache, Episodic migraine, Randomized controlled trial, 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, advanced balanced placebo design, patients with episodic migraine will receive six treatment conditions in a randomized order.
Detailed description
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.
Interventions
DRUGActive drug for acute migraine treatment
Standard dose of Sumatriptan 100 mg, which is used as an acute treatment for episodic migraine
DRUGPlacebo Oral Tablet
Inactive placebo pill (100 mg) looking like 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) sumatriptan or 2) placebo and are told that they receive a) sumatriptan or placebo, b) sumatriptan, or c) placebo
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 episodic migraine (≥ 1 and \< 15 headache days with features of migraine on at least 2-8 days per month for \> 3 months) with and without aura and diagnosed before age 50 4. Previous or active use of triptans as acute treatment for migraine 5. Ability to speak and read Danish
Exclusion criteria
1. Chronic migraine or history of chronic migraine in the last 12 months 2. Other concomitant primary headache types except for infrequent tension-type headache 3. Secondary headache disorders including medication overuse headache 4. Severe psychiatric, vascular or liver diseases 5. Opioid or barbiturate use in the month preceding screening 6. Current use of preventive migraine treatment (i.e., onabotulinum toxin A, and/or Calcitonin gene-related peptide (CGRP) monoclonal antibodies) (however, stable medical treatment with other migraine prophylactic agents is permitted, e.g. antidepressant, calcium channel blockers, beta blockers and antiepileptic drugs, 4 weeks prior to inclusion until the completion of participation in the study) 7. Contraindications or inability to tolerate triptans 8. Current substance use disorder 9. Implanted metallic or electronic device in the head 10. Cardiac pacemaker or implanted or wearable defibrillator 11. Use of illegal psychotropic drugs less than a week before participation in the study; regarding cannabis: less than four weeks before participation in the study 12. Current pregnancy or planned pregnancy (confirmed by pregnancy test and by use of safe contraception as defined by the Danish Medicines Agency) and lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Headache intensity | Immediately before and 2 hours after each treatment administration | Headache intensity rated on a 11-point Numerical Rating Scale (("How intense is your headache right now?"; 0=no pain; 10=worst imaginable pain). |
| Adverse events | 2 hours 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive and negative affect (PANAS) | Before and 2 hours after each treatment administration | 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). |
| Functional disability scale | 2 hours after each treatment administration | 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) |
| Rescue medication | 2 hours after each treatment administration | Use of rescue medication for episodic migraine (type of rescue medications, dose and time of administration) will be noted |
| Pain Freedom | 2 hours after each treatment administration | Freedom from pain will be measured as yes/no. |
| Absence of the most bothersome migraine-associated symptom | 2 hours after each treatment administration | 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. |
| Intensity of experienced adverse events | 2 hours 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). |
| Most bothersome migraine-related symptom other than headache | Immediately before each treatment administration | Participants are asked to identify their most bothersome migraine-related symptom other than headache. |
| Presence of other migraine-related symptoms | 2 hours after each treatment administration | Presence of other migraine-related symptoms, including nausea, vomiting, photophobia, phonophobia, or other symptoms is assessed dichotomously (yes/no). |
| Desire for pain relief | 2 hours after each treatment administration | 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). |
| Blinding | 2 hours after each treatment administration and after completion of the trial | 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. |
Countries
Denmark
Contacts
CONTACTSigrid Juhl Lunde, MSc, PhD
Outcome results
None listed