NCT03472092

Brief Summary

The overarching objective of this protocol is to identify and understand the neural and pain processing mechanisms by which youth with migraine improve in response to preventive treatment. The study design of this mechanistic investigation includes functional magnetic resonance imaging (fMRI), daily headache diaries, assessment of conditioned pain modulation via quantitative sensory testing, and validated psychometric assessments before and after the delivery of one of five treatments over an 8 week period \[cognitive behavioral therapy (CBT), biofeedback-assisted relaxation training (BART) and cognitive reappraisal (CR) training, amitriptyline, and placebo\]. We are examining both distinct and common pathways that may help explain the response to various preventive treatments, as well as potential predictors of outcome.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
132

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Oct 2018

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

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

First Submitted

Initial submission to the registry

March 14, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

March 21, 2018

Completed
7 months until next milestone

Study Start

First participant enrolled

October 2, 2018

Completed
6.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 24, 2025

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2025

Completed
Last Updated

August 26, 2025

Status Verified

August 1, 2025

Enrollment Period

6.4 years

First QC Date

March 14, 2018

Last Update Submit

August 25, 2025

Conditions

Keywords

headachemigrainecognitive behavioral therapyamitriptylinefunctional magnetic resonance imagingconditioned pain modulationbrain connectivitypediatrics

Outcome Measures

Primary Outcomes (2)

  • Change in functional resonance imaging (fMRI)

    For each study group, changes in distinct neural mechanisms of the brain will be compared to between baseline and post treatment (8 weeks). For each study group, the primary endpoint will be examine changes in brain connectivity and activation.

    baseline and post treatment (8 weeks post randomization)

  • Conditioned pain modulation as measured in a standard protocol using quantitative sensory testing. Employed as a predictor of headache day change in the study analytic plan

    Conditioned pain modulation as measured by quantitative sensory testing will be established for each participant. This measure involves testing pain tolerance of pressure and cold pain stimuli in a controlled manner using a standard protocol. Baseline levels of CPM for each study group will be used to predict headache day reduction for each study group. The hypothesis to be tested is that low efficiency of CPM will be differentially predictive of headache reductions following CBT in relation to other study groups.

    baseline and post treatment (8 weeks post randomization)

Study Arms (5)

Cognitive Behavioral Therapy (CBT)

EXPERIMENTAL

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

Behavioral: Cognitive Behavioral Therapy (CBT)

Placebo

PLACEBO COMPARATOR

The placebo pill will be administered once a day at home, to be taken by mouth.

Drug: Placebo

Amitriptyline

ACTIVE COMPARATOR

Amitriptyline will be administered once a day at home, to be taken by mouth. Dosage will be weight-based.

Drug: Amitriptyline

Biofeedback-Assisted Relaxation Training (BART)

ACTIVE COMPARATOR

Biofeedback-Assisted Relaxation Training (BART) is a mind and body based intervention that focuses specifically on mind and body techniques such as deep breathing, muscle relaxation, and guided imagery skills to manage pain.

Behavioral: Biofeedback-Assisted Relaxation Training (BART)

Cognitive Retraining (CR)

ACTIVE COMPARATOR

Cognitive Retraining (CR) is a mind and body based intervention that focuses on the use of tests of evidence and other cognitive strategies such as positive coping statements and pleasant activities and mindfulness to manage pain.

Behavioral: Cognitive Reappraisal Training (CR)

Interventions

This intervention will consist of 8 weekly sessions. The duration of each session is about 45 minutes and will be led by a psychologist/therapist using a manualized protocol. About half of the sessions will be conducted in person and the remaining sessions will be offered via telehealth (Skype or phone).

Also known as: CBT, coping skills, mind body relaxation
Cognitive Behavioral Therapy (CBT)

The placebo pill will be administered once a day at home for 8 weeks, to be taken by mouth with or without food under the supervision of the participant's parent or guardian. To maintain blinding, all participants will receive 1 matching capsule as a daily dose to be taken each evening during the study.

Also known as: Placebo Oral Capsule
Placebo

Amitriptyline will be administered once a day at home for 8 weeks, to be taken by mouth with or without food under the supervision of the participant's parent or guardian. To maintain blinding, all participants will receive 1 matching capsule as a daily dose to be taken each evening during the study. For this study, a dose of 0.25 mg/kg/day will be provided for the 1st 2 weeks, followed by a dose of 0.5 mg/kg/day for 2 weeks, 0.75 mg/kg/day for 2 weeks and a maximum dose of 1.0 mg/kg/day for 2 weeks based on tolerability. Participants experiencing tolerability issues, may be held a current dose rather than titrated to the next dosage if deemed appropriate by the study doctor.

Also known as: Elavil
Amitriptyline

This intervention will consist of 8 weekly sessions. The duration of each session is about 45 minutes and will be led by a psychologist/therapist using a manualized protocol. About half of the sessions will be conducted in person and the remaining sessions will be offered via telehealth (Skype or phone).

Biofeedback-Assisted Relaxation Training (BART)

This intervention will consist of 8 weekly sessions. The duration of each session is about 45 minutes and will be led by a psychologist/therapist using a manualized protocol. About half of the sessions will be conducted in person and the remaining sessions will be offered via telehealth (Skype or phone).

Cognitive Retraining (CR)

Eligibility Criteria

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

You may qualify if:

  • Diagnosis: Migraine with or without aura or chronic migraine that meets the International Classification of Headache Disorders, 3rd Edition (beta) (ICHD-3b) criteria
  • Frequency: Headache frequency based upon prospective headache diary of 28 days must be ≥ 8 and ≤ 28
  • PedMIDAS: PedMIDAS Disability Score \> 10, indicating at least mild disruption in daily activities and \< 140, indicating extreme disability that may require more comprehensive, multi-component therapy
  • English speaking: able to complete interviews and questionnaires in English

You may not qualify if:

  • Continuous migraine defined as an unrelenting headache for a 28 day period
  • Weight less than 30 kg or greater than 120 kg, or weight/size incompatible with magnetic resonance imaging (MRI) scanner
  • Must agree not to take non-specific acute medication, such as nonsteroidal anti-inflammatory drugs (NSAIDS) (e.g., ibuprofen), more than 3 times per week, or migraine specific acute medications, such as triptans, more than 6 times per month
  • No current prophylactic anti-migraine medication within a period equivalent to \< 5 half-lives of that medication before entering the screening phase, and agree to not begin a migraine prevention medication during the study period
  • Current use of the following medications/products: opioids, antipsychotics, antimanics, barbiturates, benzodiazepines, muscle relaxants, sedatives, tramadol, nutraceuticals
  • Known history of allergic reaction or anaphylaxis to amitriptyline
  • Abnormal findings on electrocardiogram (ECG) at baseline, particularly lengthening of the QT interval ≥ 450 msec
  • Orthodontic braces, metallic or electronic implants, or other metal objects in the body which obscure or interfere with the MRI, or pose a risk from heating, movement, or malfunction in the MRI environment
  • Claustrophobia
  • Youth who are pregnant, or those who are sexually active and not using a medically accepted form of contraception (barrier or hormonal methods)
  • Diagnosis of epilepsy or other neurological diseases
  • Inability to learn how to swallow pills using behavioral techniques (if indicated)
  • Present psychiatric disease as defined by the Diagnostic and Statistical Manual (DSM) IV (e.g. psychosis, bipolar disorder, major depression, generalized anxiety disorder), alcohol or drug dependence, or documented developmental delays or impairments (e.g., autism, cerebral palsy, attention deficit hyperactivity disorder (ADHD), or mental retardation) that, in the opinion of the investigator, would interfere with adherence to study requirements or safe participation in the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Migraine DisordersHeadache

Interventions

Cognitive Behavioral TherapyCoping SkillsAmitriptyline

Condition Hierarchy (Ancestors)

Headache Disorders, PrimaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesPainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

  • Scott Powers, PhD

    Children's Hospital Medical Center, Cincinnati

    PRINCIPAL INVESTIGATOR
  • Robert Coghill, PhD

    Children's Hospital Medical Center, Cincinnati

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Behavioral therapy assignment is known to the treating therapist/care provider. Placebo and amitriptyline are double blinded. Participant will be aware they are either assigned to behavioral or pill therapy.
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Model Details: Mechanistic/basic science project seeking to identify the neural mechanisms by which youth with migraine improve in response to preventive treatment.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 14, 2018

First Posted

March 21, 2018

Study Start

October 2, 2018

Primary Completion

February 24, 2025

Study Completion

June 30, 2025

Last Updated

August 26, 2025

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will not share

Locations