NCT05654012

Brief Summary

Aim 1. To identify psychophysical and neural factors predicting migraine onset in adolescents Aim 2a. To determine hormonal, psychophysical, and neural changes associated with migraine onset. Aim 2b. To identify the temporal relationships between hormonal, psychophysical, and neural changes preceding vs. following migraine onset. Aim 3. To identify psychophysical and neural factors predicting migraine prognosis in adolescents with migraine.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
250

participants targeted

Target at P75+ for not_applicable

Timeline
47mo left

Started Jun 2023

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

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 Progress43%
Jun 2023Mar 2030

First Submitted

Initial submission to the registry

November 28, 2022

Completed
18 days until next milestone

First Posted

Study publicly available on registry

December 16, 2022

Completed
6 months until next milestone

Study Start

First participant enrolled

June 1, 2023

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 15, 2028

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 15, 2030

Last Updated

August 13, 2025

Status Verified

August 1, 2025

Enrollment Period

4.8 years

First QC Date

November 28, 2022

Last Update Submit

August 12, 2025

Conditions

Outcome Measures

Primary Outcomes (2)

  • Number of participants with a new diagnosis of migraine

    Multivariable regression analyses with baseline psychophysical, and neural factors will be used to identify predictors for migraine diagnosis and headache frequency. For Aim 1a, the primary outcome is migraine diagnosis (binary variable based on the physician's diagnosis), the independent variables are baseline PPT, CPM response, and FC of the right amygdala, and the controlling factors are race and age.

    2 years

  • Number of participants with a new diagnosis of migraine

    Multivariable regression analyses with baseline psychophysical, and neural factors will be used to identify changes related to migraine diagnosis. For Aim 1b, the primary outcome measure is headache frequency (7-day average based on the headache diary completed before the 2-year follow-up visit), the independent variable is FC of the right amygdala, the controlling factors are the time of migraine diagnosis (at 1-year or 2-year study visit), race, and age. Since all participants will be at early pubertal maturation and pre-menarche at baseline, pubertal status will not be controlled for in this aim.

    2 Years

Study Arms (2)

Family History of Migraine

OTHER

This group has a first degree relative diagnosed with migraine.

Device: MRIDevice: Thermal StimuliDevice: Pressure stimuliBehavioral: Pain ratingsBehavioral: Pressure pain thresholds (PPT)Behavioral: Conditioned pain modulation (CPM) efficiencyDiagnostic Test: Hormonal assessmentBehavioral: Migraine-related measuresBehavioral: Neural assessmentsDiagnostic Test: Pubertal status

No Family History of Migraine

OTHER

This group does not have a first or second degree relative diagnosed with migraine.

Device: MRIDevice: Thermal StimuliDevice: Pressure stimuliBehavioral: Pain ratingsBehavioral: Pressure pain thresholds (PPT)Behavioral: Conditioned pain modulation (CPM) efficiencyDiagnostic Test: Hormonal assessmentBehavioral: Migraine-related measuresBehavioral: Neural assessmentsDiagnostic Test: Pubertal status

Interventions

MRIDEVICE

Grey Matter Volume (T1) Resting state BOLD

Family History of MigraineNo Family History of Migraine

The Thermal Sensory Analyzer (TSA-II or PATHWAY platform - Medoc, Ramat Yishai, Israel) will be used to safely deliver heat and cold stimuli. These devices can deliver relatively complex stimuli via computer control. All targeted stimulus temperatures will be less than 50°C, and participants will be free to remove their arm or leg at any time from the thermode. Noxious cold stimuli will also be delivered with a plastic water container or a water bath (FISHER, USA). Participants will be free to pull out of the water bath at any time.

Family History of MigraineNo Family History of Migraine

Pressure stimuli will be applied by using a handheld algometer (Wagner Instruments) or the Pressure Algometer (Medoc, Ramat Yishai, Israel). These devices have a round probe that allows quantifying the amount of pressure that is being applied. The Pressure Algometer allows a real-time visual feedback to control and monitor applied pressure rates. Pressure will be applied to the lower leg, volar forearm, or trapezius.

Family History of MigraineNo Family History of Migraine
Pain ratingsBEHAVIORAL

Pain intensity and pain unpleasantness ratings will be assessed by numerical rating scale (ranging from 0- no pain/unpleasantness to- 10 or 100 the most intense/unpleasantness pain imaginable) and by mechanical and computerized visual analog scales (VAS which ranges between ''no pain sensation'' and ''most intense pain imaginable'').

Family History of MigraineNo Family History of Migraine

Pressure will be increased continually and participants will be instructed to press a button the first moment they feel pain from the pressure stimulus.

Family History of MigraineNo Family History of Migraine

The CPM paradigm assesses endogenous inhibitory pain modulation efficiency related to spatial filtering of nociceptive information.

Family History of MigraineNo Family History of Migraine
Hormonal assessmentDIAGNOSTIC_TEST

Blood samples will be collected for analyses of sex hormone levels

Family History of MigraineNo Family History of Migraine

Adolescents with migraine will complete questions regarding their headache frequency and migraine symptoms.

Family History of MigraineNo Family History of Migraine

MRI and fMRI scans

Family History of MigraineNo Family History of Migraine
Pubertal statusDIAGNOSTIC_TEST

Pubertal status will be assessed using the self-reported Physical Developmental Scale-

Family History of MigraineNo Family History of Migraine

Eligibility Criteria

Age10 Years - 13 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Age 10-13
  • Males or females (biological sex)
  • Not diagnosed with migraine or having migraine symptoms
  • With a first degree relative diagnosed with migraine (for the Fam-His group) or without a first or a second degree relative diagnosed with migraine (for the No-Fam-His group)
  • Age 10-13
  • Males or females (biological sex)
  • Diagnosed with migraine or having migraine symptoms
  • Migraine duration \> 6 months
  • Without preventative treatment or with stable preventative treatment for migraine (no change in intervention in the last 6 months)

You may not qualify if:

  • Participants will not be enrolled if any of the following criteria exist and based on the investigator discretion:
  • Diagnosis of any chronic pain syndrome
  • Diagnosis of a neurological, developmental, pubertal, or psychiatric disorder
  • Taking pain or psychiatric medications regularly
  • Having an MRI contraindication such as metal in the body or claustrophobia
  • Not able to understand and communicate in English
  • Participants will not be enrolled if any of the following criteria exist and based on the investigator discretion:
  • Diagnosis of any chronic pain syndrome other than migraine
  • Diagnosis of a neurological, developmental, pubertal, or psychiatric disorder
  • Having an MRI contraindication such as metal in the body or claustrophobia
  • Not able to understand and communicate in English

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

MeSH Terms

Conditions

Migraine Disorders

Interventions

carboxypeptidase MEfficiency

Condition Hierarchy (Ancestors)

Headache Disorders, PrimaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

Organization and AdministrationHealth Services Administration

Study Officials

  • Hadas Nahman-Averbuch, PhD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Alana McMichael, MA

CONTACT

Hadas Nahman-Averbuch

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Asst Prof of Anesthesiology

Study Record Dates

First Submitted

November 28, 2022

First Posted

December 16, 2022

Study Start

June 1, 2023

Primary Completion (Estimated)

March 15, 2028

Study Completion (Estimated)

March 15, 2030

Last Updated

August 13, 2025

Record last verified: 2025-08

Locations