Clinical trial NCT06972056: Comparative Effectiveness of Migraine Preventive Medications: The APT Comparison Study
Official title: A Comparative Effectiveness Study of Oral Medications Used for Migraine Prevention: The APT Comparison Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Migraine
Keywords: Migraine
Migraine with aura
Migraine prevention
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: University of Iowa
name: Patient-Centered Outcomes Research Institute
name: AbbVie
First posted: 2025-05-14
Enrollment: 1335
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This goal of this study is to compare three medications used for migraine preventive treatment.

This study will compare atogepant, a newer migraine preventive medication, with two older preventive medications, topiramate and propranolol. It will be determined if one works better and is more tolerable than the others.

Research participants will:

* Be randomly assigned to one of the three medications.
* Provide information about their migraine pattern using a daily headache diary and during research visits.

Detailed description: This is a prospective, randomized, comparative effectiveness clinical trial of atogepant, propranolol, and topiramate for the prevention of migraine in adults.

Eligible participants will provide information in a daily headache diary for four weeks. If after those four weeks they are still eligible for the study, they will be randomized to one of the study medications and receive study medication for twelve weeks.

Research visits occur at baseline, four weeks later for the randomization visit, and then at post-randomization weeks four, eight, twelve, twenty-four, and forty-eight.

Participants provide data using a headache diary (first 16 weeks of the study) and during research visits.

The primary endpoint is the proportion of participants in each treatment group who are "treatment responders" defined as completing the first twelve weeks of the study on the assigned medication and having a 50% or greater reduction in moderate severe headache days during weeks 9-12 post-randomization compared to the four weeks pre-randomization.

Eligibility criteria: Inclusion Criteria:

* Adults, 18-70 years of age at the time of enrollment
* Migraine with aura, migraine without aura, and/or chronic migraine; according to ICHD-3 diagnostic criteria. (Those with daily or continuous headaches are not excluded.)
* Migraine onset prior to 50 years of age
* Migraine present for at least 12 months at the time of enrollment
* At least four "moderate to severe headache days" per month (by patient self-report and then confirmed during four-week pre-randomization headache diary phase) A "moderate to severe headache day" is defined as a day during which there is a headache of moderate to severe intensity that lasts for at least four hours, or a day on which a migraine-specific acute medication is taken to treat headache.
* If already taking a migraine preventive treatment, willing to continue with that treatment without dose change during the first 16 weeks of the study, including the 4-week run-in phase and 12-week randomized phase.
* Not pregnant or breastfeeding
* Women of childbearing potential must agree to use effective methods of contraception to reduce the risk of pregnancy.
* Willingness and ability to provide informed consent.
* Willingness and ability to complete all research visits.

Exclusion Criteria:

* Contraindications to taking atogepant, propranolol, or topiramate.
* Currently taking atogepant, propranolol, or topiramate\*
* Previously took atogepant, propranolol, or topiramate\*
* Unwillingness to take atogepant, topiramate, or propranolol.
* Current use of a CGRP-targeting preventive medication or beta-blocker
* Migraine with brainstem aura
* Hemiplegic migraine
* Retinal migraine
* Migraine aura without headache (exclusively)
* Pure menstrual migraine
* Trigeminal autonomic cephalalgias
* Facial neuralgias
* Secondary headache disorders (medication overuse headache is not an exclusion)
* Migraine preventive treatment has been started or dose has been changed within 12 weeks prior to potential enrollment.
* Used opioids or butalbital on five or more days per month on average for at least 3 months prior to enrollment.
* Current or past epilepsy
* Severe hepatic impairment
* Moderate or more severe renal impairment \* Occasional as needed use of propranolol, currently or in the past, is not an exclusion, such as taking as needed propranolol for treatment of anxiety.

Primary outcomes:
measure: Treatment Responder (atogepant vs. topiramate; atogepant vs. propranolol)
timeFrame: Weeks 9-12 post-randomization compared to the 4 weeks prior to randomization
Secondary outcomes:
measure: Migraine Specific Quality-of-Life - Role Function-Restrictive
timeFrame: Week 12 post-randomization vs. baseline
measure: Treatment Responder (propranolol vs. topiramate)
timeFrame: Weeks 9-12 post-randomization vs. the 4 weeks prior to randomization
measure: Headache Impact Test-6 (HIT-6)
timeFrame: week 12 post-randomization vs. baseline
measure: Medication-Related Adverse Events
timeFrame: All 12 weeks of the randomized treatment phase
Other outcomes:
Locations:
city: Flagstaff
country: United States
facility: Northern Arizona Healthcare
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Los Angeles
country: United States
facility: USC Keck
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Todd J Schwedt, M.D.
role: PRINCIPAL_INVESTIGATOR
References: