Clinical trial NCT06617832: Trial Designs for Evaluating Migraine Treatment
Official title: Trial Designs for Evaluating Migraine Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Migraine with Aura
Migraine Without Aura
Headache, Migraine
Keywords: Headache
Episodic migraine
Randomized controlled trial
Balanced placebo design
Treatment effects
Adverse events
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2024-10-01
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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
Primary purpose: BASIC_SCIENCE

Brief summary: The study aims to estimate treatment effects in randomized controlled trials (RCT) and a balanced placebo design (BPD) to specify how contextual and psychological factors interact in acute migraine treatment and influence adverse event occurrence. Using a clinical within-subjects 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 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 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 if the magnitude of the drug effect differs when estimated based on the RCT design and when based on BPD, conditioning on the information provided to the recipient. Additionally, it will also be tested if 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.

Eligibility criteria: 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 \&lt; 15 headache days with features of migraine on at least 2-8 days per month for \&gt; 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 baseline 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

Primary outcomes:
measure: Headache intensity
timeFrame: 2 hours from each treatment administration
measure: Adverse events
timeFrame: 2 hours from each treatment administration
Secondary outcomes:
measure: Positive and negative affect (PANAS)
timeFrame: Before and 2 hours after each treatment administration
measure: Functional disability scale
timeFrame: Before and 2 hours after each treatment administration
measure: Rescue medication
timeFrame: 2 hours from each treatment administration
measure: Pain Freedom
timeFrame: 2 hours from each treatment administration
measure: Absence of the most bothersome symptom
timeFrame: 2 hours from each treatment administration
measure: Intensity of experienced adverse events
timeFrame: 2 hours (from each treatment administration)
Other outcomes:
measure: Expectations
timeFrame: Before administration of each treatment condition
Locations:
city: Aarhus C
country: Denmark
facility: Dept. of Psychology and Behavioural Sciences
city: Aarhus N
country: Denmark
facility: Department of Clinical Medicine, Aarhus University Hospital
Study officials:
References: