Trial Designs for Evaluating Migraine Treatment

Overview

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

• Drug Active drug for acute migraine treatment
  Standard dose of Sumatriptan 100 mg, which is used as an acute treatment for episodic migraine
• Drug Placebo Oral Tablet
  Inactive placebo pill (100 mg) looking like the active drug

Primary outcome measures

• Headache intensity [Time frame: Immediately before and 2 hours after each treatment administration]
• Adverse events [Time frame: 2 hours after each treatment administration]

Secondary outcome measures (10)

• Positive and negative affect (PANAS) [Time frame: Before and 2 hours after each treatment administration]
• Functional disability scale [Time frame: 2 hours after each treatment administration]
• Rescue medication [Time frame: 2 hours after each treatment administration]
• Pain Freedom [Time frame: 2 hours after each treatment administration]
• Absence of the most bothersome migraine-associated symptom [Time frame: 2 hours after each treatment administration]
• Intensity of experienced adverse events [Time frame: 2 hours after each treatment administration]
• Most bothersome migraine-related symptom other than headache [Time frame: Immediately before each treatment administration]
• Presence of other migraine-related symptoms [Time frame: 2 hours after each treatment administration]
• Desire for pain relief [Time frame: 2 hours after each treatment administration]
• Blinding [Time frame: 2 hours after each treatment administration and after completion of the trial]

Eligibility criteria

Inclusion criteria

• Adults (18-65 years)
• ≥ 1-year history of migraine with or without aura according to the International Classification of Headache Disorders (ICHD-3) diagnostic criteria
• 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
• Previous or active use of triptans as acute treatment for migraine
• Ability to speak and read Danish

Exclusion criteria

• Chronic migraine or history of chronic migraine in the last 12 months
• Other concomitant primary headache types except for infrequent tension-type headache
• Secondary headache disorders including medication overuse headache
• Severe psychiatric, vascular or liver diseases
• Opioid or barbiturate use in the month preceding screening
• 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)
• Contraindications or inability to tolerate triptans
• Current substance use disorder
• Implanted metallic or electronic device in the head
• Cardiac pacemaker or implanted or wearable defibrillator
• 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
• Current pregnancy or planned pregnancy (confirmed by pregnancy test and by use of safe contraception as defined by the Danish Medicines Agency) and lactation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Basic science

Study locations

Denmark · 2 centers

• Dept. of Psychology and Behavioural Sciences — Aarhus C
• Department of Neurology, Aarhus University Hospital — Aarhus N

Identifiers

NCT: NCT06617832 · UAarhus_Acute migraine

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗