New Methods for Evaluating Preventive 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, balanced placebo design, patients with chronic migraine will receive four treatment conditions in a randomized order.

Detailed description

The existing paradigm for testing the effect of treatment 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 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 (BPD) 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.

Interventions

• Drug Active drug for chronic migraine treatment.
  Standard dose of Fremanezumab, 225 mg (Ajovy) injected subcutaneously
• Drug Placebo Subcutaneous injection
  Inactive placebo (saline) injected subcutaneously in the same volume as the active drug

Primary outcome measures

• Mean change in headache intensity [Time frame: Measured every day during the 8 month trial period]
• Mean change in moderate/severe headache days [Time frame: Measured every day during the 8 month trial period]
• Adverse events [Time frame: 24 hours, 14 and 28 days after each treatment administration]

Secondary outcome measures (8)

• Migraine days [Time frame: Measured every day during the 8 month trial period]
• Acute treatment utilization [Time frame: Measured every day during the 8 month trial period]
• Positive and negative affect (PANAS) [Time frame: Pre-treatment and 28 days after each treatment administration]
• Hospital Anxiety and Depression Scale (HADS) [Time frame: Pre-treatment and 28 days after each treatment administration]
• Quality of life (SF-12) [Time frame: Pre-treatment and 28 days after each treatment administration]
• HIT-6 [Time frame: Pre-treatment and 28 days after each treatment administration]
• Intensity of experienced adverse events [Time frame: 24 hours, 14 days and 28 days after each treatment administration]
• Blinding [Time frame: 28 days 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 chronic migraine (headache occurring ≥ 15 days per month for > 3 months, which on at least 8 days per month has the features of migraine headache) diagnosed before age 65
• Eligibility for preventive migraine treatment
• Ability to speak and read Danish

Exclusion criteria

• Use of onabotulinumtoxinA as preventive migraine treatment during the 4 months before inclusion
• Use of other preventive migraine treatment except CGRP antagonists (However, participants are allowed to be on two stable preventive medication (antidepressant, calcium channel blockers, beta blockers or antiepileptic)- 2 months prior to inclusion until end of study), devices for migraine prevention such as transcranial magnetic stimulation and use of nerve blocks 3 months prior to inclusion
• Use of opioid or barbiturate medications in the last four weeks before inclusion
• Secondary headache disorders including medication overuse headache
• Severe psychiatric, vascular disease, or known liver disease
• Alcohol abuse or substance abuse
• Current or planned pregnancy 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

• Department of Psychology and Behavioral sciences, Aarhus BSS, Aarhus University — Aarhus C
• Department of Neurology, Aarhus University Hospital — Aarhus N

Identifiers

NCT: NCT07071506 · UAarhus_Chronic migraine

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗