NCT06972056

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,335

participants targeted

Target at P75+ for phase_4

Timeline
43mo left

Started Jul 2025

Longer than P75 for phase_4

Geographic Reach
1 country

35 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress21%
Jul 2025Dec 2029

First Submitted

Initial submission to the registry

April 29, 2025

Completed
15 days until next milestone

First Posted

Study publicly available on registry

May 14, 2025

Completed
2 months until next milestone

Study Start

First participant enrolled

July 9, 2025

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2029

Expected
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2029

Last Updated

May 22, 2026

Status Verified

May 1, 2026

Enrollment Period

3.6 years

First QC Date

April 29, 2025

Last Update Submit

May 20, 2026

Conditions

Keywords

MigraineMigraine with auraMigraine prevention

Outcome Measures

Primary Outcomes (1)

  • Treatment Responder (atogepant vs. topiramate; atogepant vs. propranolol)

    This study will use a "treatment responder" primary endpoint that will investigate medication superiority using a combination of headache frequency reduction and medication persistence. To achieve this, a binary endpoint of treatment response will be used that combines effectiveness and medication persistence at the individual level, with success defined as: 1. Completing the first 12 weeks of the study on the assigned medication without discontinuation due to any reason, AND 2. Having a 50% or greater reduction in moderate to severe headache days during weeks 9-12 compared to a 4-week pre-randomization period.

    Weeks 9-12 post-randomization compared to the 4 weeks prior to randomization

Secondary Outcomes (4)

  • Migraine Specific Quality-of-Life - Role Function-Restrictive

    Week 12 post-randomization vs. baseline

  • Treatment Responder (propranolol vs. topiramate)

    Weeks 9-12 post-randomization vs. the 4 weeks prior to randomization

  • Headache Impact Test-6 (HIT-6)

    week 12 post-randomization vs. baseline

  • Medication-Related Adverse Events

    All 12 weeks of the randomized treatment phase

Study Arms (3)

Atogepant

ACTIVE COMPARATOR

Participants who are randomized to this arm will take up to 60mg daily for 12 weeks.

Drug: Atogepant 60 mg

Propranolol

ACTIVE COMPARATOR

Participants randomized to this arm will take up to 160 mg daily for 12 weeks.

Drug: Propranolol 160 mg

Topiramate

ACTIVE COMPARATOR

Participants randomized to this arm will take up to 100 mg daily for 12 weeks .

Drug: Topiramate 100 mg

Interventions

Atogepant at a dose up to 60 mg daily.

Also known as: Qulipta
Atogepant

Daily propranolol up to 80 mg twice daily.

Also known as: Inderal
Propranolol

Daily topiramate, up to 50 mg twice daily

Also known as: Topamax
Topiramate

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (35)

Northern Arizona Healthcare

Flagstaff, Arizona, 86001, United States

RECRUITING

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

USC Keck

Los Angeles, California, 90033, United States

RECRUITING

Clinical Research Institute

Los Angeles, California, 90048, United States

RECRUITING

Desert Physicians Medical Group

Palm Springs, California, 92262, United States

RECRUITING

The Neurology Group

Pomona, California, 91767, United States

RECRUITING

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Memorial Healthcare

Hollywood, Florida, 33021, United States

RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, 32066, United States

RECRUITING

Apple Med Research

Miami, Florida, 33126, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

NOT YET RECRUITING

Clinical Trials of New England

Hyde Park, Massachusetts, 02136, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University St Louis

St Louis, Missouri, 63110, United States

RECRUITING

Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

Advanced Research Institute Reno

Reno, Nevada, 89511, United States

RECRUITING

JFK Neuroscience Institute

Edison, New Jersey, 08820, United States

RECRUITING

Nuvance Health Institute

Kingston, New York, 12401, United States

RECRUITING

Northwell Health

Manhasset, New York, 11030, United States

RECRUITING

Mt Sinai Icahn School of Medicine

New York, New York, 10029, United States

RECRUITING

Onsite Clinical Solutions Park Cedar Dr.

Charlotte, North Carolina, 28210, United States

NOT YET RECRUITING

Onsite Clinical Solutions Mecklenburg

Charlotte, North Carolina, 28211, United States

NOT YET RECRUITING

Onsite Clinical Solutions Ballantyne

Charlotte, North Carolina, 28277, United States

NOT YET RECRUITING

Onsite Clinical Solutions Salisbury

Salisbury, North Carolina, 28144, United States

NOT YET RECRUITING

Wake Forest University Health

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

Advanced Research Institute

Portland, Oregon, 97223, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Brown University Health

Providence, Rhode Island, 02903, United States

RECRUITING

Vanderbilt Medical Center

Nashville, Tennessee, 37215, United States

RECRUITING

DHR Health Headache Center

McAllen, Texas, 78504, United States

RECRUITING

Advanced Research Institute Ogden

Ogden, Utah, 84405, United States

RECRUITING

West Virginia University

Morgantown, West Virginia, 26506, United States

RECRUITING

Marshfield Clinic Research Institute

Marshfield, Wisconsin, 54449, United States

RECRUITING

The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Migraine DisordersMigraine with Aura

Interventions

atogepantPropranololTopiramate

Condition Hierarchy (Ancestors)

Headache Disorders, PrimaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

PhenoxypropanolaminesPropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPolycyclic CompoundsFructoseHexosesMonosaccharidesSugarsCarbohydratesKetoses

Study Officials

  • Todd J Schwedt, M.D.

    Mayo Clinic

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael R Leonard, MDiv

CONTACT

Dani C Smith, M.S.

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

April 29, 2025

First Posted

May 14, 2025

Study Start

July 9, 2025

Primary Completion (Estimated)

March 1, 2029

Study Completion (Estimated)

December 1, 2029

Last Updated

May 22, 2026

Record last verified: 2026-05

Data Sharing

IPD Sharing
Will share

As per PCORI data sharing policy

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
Time Frame
Summer 2030 (anticipated)
Access Criteria
Per PCORI data sharing policy

Locations