NCT05889624

Brief Summary

This comparative effectiveness study will clarify current first-line preventive treatment approaches for use by neurologists, psychologists, and primary care providers in the context of real world care, and will demonstrate the feasibility of Cognitive Behavioral Therapy (CBT) via telehealth for youth with migraine. The focus is on applying evidence-based care and enhancing access to it. CBT via telehealth while taking a clinically-prescribed, pill-based prevention therapy (amitriptyline) will be compared to CBT via telehealth alone.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
400

participants targeted

Target at P75+ for not_applicable

Timeline
20mo left

Started Aug 2023

Longer than P75 for not_applicable

Geographic Reach
1 country

15 active sites

Status
recruiting

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

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress62%
Aug 2023Dec 2027

First Submitted

Initial submission to the registry

May 10, 2023

Completed
26 days until next milestone

First Posted

Study publicly available on registry

June 5, 2023

Completed
3 months until next milestone

Study Start

First participant enrolled

August 22, 2023

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2027

Expected
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2027

Last Updated

March 6, 2026

Status Verified

March 1, 2026

Enrollment Period

3.9 years

First QC Date

May 10, 2023

Last Update Submit

March 4, 2026

Conditions

Keywords

headachemigrainecognitive behavioral therapypediatricsdiaphragmatic breathingprogressive muscle relaxationimageryrelaxationbiofeedback

Outcome Measures

Primary Outcomes (2)

  • Change in number of headache days

    This outcome measures whether there is a 50% reduction in the number of headaches days based on a self reported daily headache diary, per 28-day period, between the two arms.

    baseline to weeks 4-8 to weeks 20-24 (post treatment)

  • Reduction to a PedMIDAS score of 20 or less

    The PedMIDAS scale which evaluates the impact of headaches in school, home, play, and social activities, is comprised of six items that pertain to days missed in various activities over the past 90 days. Questions are answered by the youth in consultation with their parents and reviewed by study staff. The PedMIDAS scale is administered at baseline (covering the three months prior to enrollment) and at the endpoint visit (covering last three months of enrollment). This outcome measures whether there is a reduction in migraine related disability measured by the Pediatric Migraine Disability Scale (PedMIDAS) between the two arms. A reduction to a score of 20 or less, indicating mild impact of less is a meaningful outcome for patients and families and considered clinically significant.

    baseline to weeks 20-24 (post treatment)

Secondary Outcomes (4)

  • Change in absolute reduction in severe headache days

    baseline to weeks 20-24 (post treatment)

  • Change in absolute headache days

    baseline to weeks 4-8 to weeks 20-24 (post treatment)

  • Change in absolute headache disability score on PedMIDAS

    baseline to weeks 20-24 (post treatment)

  • Safety and tolerability of treatments (CBT and Amitriptyline)

    randomization to weeks 20-24 (post treatment)

Other Outcomes (3)

  • Exploratory: Change in self-reported physical and psychosocial functioning (functional impact)

    baseline to weeks 20-24 (post treatment)

  • Exploratory: Change in self-reported quality of life

    baseline to weeks 20-24 (post treatment)

  • Exploratory: Impact of social determinants of health

    baseline

Study Arms (2)

CBT while taking a clinically-prescribed, pill-based prevention therapy (amitriptyline)

EXPERIMENTAL

This intervention consists of Cognitive Behavioral (CBT), a mind and body based intervention using education on gate control theory of pain, behavioral strategies such as muscle relaxation, activity pacing, and cognitive strategies including distraction, problem solving, and using calming self-statements. This arm will also take a daily oral dose of Amitriptyline, which will be clinically prescribed and managed by the patient's headache provider.

Behavioral: CBTDrug: Amitriptyline

CBT alone

EXPERIMENTAL

This intervention arm consists of 6 Cognitive Behavioral Therapy (CBT), a mind and body based intervention using education on gate control theory of pain, behavioral strategies such as muscle relaxation, activity pacing, and cognitive strategies including distraction, problem solving, and using calming self-statements.

Behavioral: CBT

Interventions

CBTBEHAVIORAL

During an 8-week active treatment, participants will receive 6 telehealth CBT sessions, followed by a maintenance phase (16 weeks) when participants will receive 3 "booster" CBT sessions. The sessions will be conducted by teletherapists from the Clinical Coordinating Center at Cincinnati Children's using a standardized treatment manual. A parent/legal guardian will be included in 2 sessions teaching ways to be active coaches, encouraging use of effective coping skills and refraining from reinforcement of maladaptive coping. Each session will be about 45 minutes.

Also known as: Cognitive Behavioral Therapy
CBT aloneCBT while taking a clinically-prescribed, pill-based prevention therapy (amitriptyline)

During an 8-week active treatment, participants will begin taking a daily pill (amitriptyline) prescribed and managed clinically by the site headache provider. Amitriptyline will be taken once a day before bedtime. The weight based dosage will gradually be increased based on tolerability and a standardized titration protocol during the 8 week active treatment. The participant will remain on a maximum tolerated dose for the final 16 weeks (maintenance).

CBT while taking a clinically-prescribed, pill-based prevention therapy (amitriptyline)

Eligibility Criteria

Age10 Years - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Diagnosis: Migraine with or without aura that meets the International Classification of Headache Disorders (ICHD) criteria 5 or presentation of continuous headache that includes migranous episodes based upon headache history obtained by site PI or designee. (includes presentation with or without medication overuse headache as well)
  • Headache Frequency: 4 or more headache days based upon prospective headache diary of 28 days prior to randomization
  • Amitriptyline Eligible: Site PI or medical staff determined participant to be eligible for clinical prescription of amitriptyline as a preventive treatment for migraine
  • English fluency: Able to complete the study visits and questionnaires in English

You may not qualify if:

  • Current treatment includes amitriptyline and/or CBT specific to headache care
  • Current prescribed preventive antimigraine medication within a period equivalent to \< 5 half-lives of that medication before entering the baseline phase
  • Current treatment with onabotulinumtoxinA (Botox) or CGRP-based monoclonal antibody medications for migraine prevention
  • Youth who are pregnant
  • Report of current or ongoing suicidal thoughts. Suicide attempt within the past six months. History of bipolar disorder, prolonged QT, or pre-existing significant constipation or gastroparesis
  • Any and all other diagnoses or conditions which, in the opinion of the site investigator, would prevent the patient from being a suitable candidate for the study or interfere with the medical care needs of the participant

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

University of Alabama at Birmingham Children's of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Phoenix Children's Hospital - Barrow Neurological Institute

Phoenix, Arizona, 85016-7710, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94115, United States

RECRUITING

University of Colorado/Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Nemours Children's Health System

Wilmington, Delaware, 19810, United States

RECRUITING

Clinical Integrative Research Center of Atlanta, Inc

Atlanta, Georgia, 30328, United States

RECRUITING

University of Louisville Health/Norton

Louisville, Kentucky, 40292, United States

RECRUITING

Louisiana State Univ/Children's Hospital of New Orleans

New Orleans, Louisiana, 70118-5720, United States

RECRUITING

Dent Neurological Institute

Amherst, New York, 14226, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Nationwide Childrens

Columbus, Ohio, 43205, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Tennessee Health Science Center/ LeBonheur Children's Hospital

Memphis, Tennessee, 38103, United States

RECRUITING

Dell Children's Hospital-UT Health

Austin, Texas, 78712, United States

RECRUITING

Marshall Health

Huntington, West Virginia, 25701, United States

RECRUITING

MeSH Terms

Conditions

HeadacheHeadache DisordersMigraine DisordersMigraine with AuraMigraine without Aura

Interventions

Cognitive Behavioral TherapyAmitriptyline

Condition Hierarchy (Ancestors)

PainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesHeadache Disorders, Primary

Intervention Hierarchy (Ancestors)

Behavior TherapyPsychotherapyBehavioral Disciplines and ActivitiesDibenzocycloheptenesBenzocycloheptenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Study Officials

  • Scott Powers, PhD

    Cincinnati Childrens Medical Center, Cincinnati

    PRINCIPAL INVESTIGATOR

Central Study Contacts

LeighAnn Chamberlin, MEd

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Masking Details
Only the principal investigator will remain blinded to the randomization assignment. All other study staff including the project manager, assistant project manager, study statistician, site investigators and study staff, participants, and their parents will be aware of the treatment assignment.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 10, 2023

First Posted

June 5, 2023

Study Start

August 22, 2023

Primary Completion (Estimated)

July 31, 2027

Study Completion (Estimated)

December 31, 2027

Last Updated

March 6, 2026

Record last verified: 2026-03

Locations