Puberty, Sex Hormones and Pain Sensitivity in Adolescents With Migraine

NCT05738213 | Active Not Recruiting

• 2 other identifiers: 202208057Seed Pediatric Research Grant
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to investigate the relationships between sex hormone levels and experimental pain sensitivity and migraine severity will be examined.

Conditions

Migraine

Keywords

pain; puberty; sex hormones

Outcome Measures

Primary Outcomes (2)

• Conditioned pain modulation (CPM) response

  This psychophysical test examine the inhibitory pain modulation efficiency. In this test, pressure pain thresholds (measures by kilopascal) are assessed before and during immersion of the foot in cold water.

  Baseline

• Sex Hormones

  Testosterone levels

  Baseline

Secondary Outcomes (2)

• Sex hormone assessments

  Baseline

• Migraine specific measures

  Baseline

Study Arms (2)

Migraine

ACTIVE COMPARATOR

Adolescents with a migraine diagnosis

Device: Thermal stimuli; Device: Pressure stimuli; Behavioral: Pain ratings; Behavioral: Pressure pain thresholds (PPT); Behavioral: Conditioned pain modulation (CPM) response; Behavioral: PedMIDAS (Pediatric Migraine Disability Assessment); Diagnostic Test: Hormonal assessment; Other: Pubertal status

Healthy control

PLACEBO COMPARATOR

Adolescents without a migraine diagnosis

Device: Thermal stimuli; Device: Pressure stimuli; Behavioral: Pain ratings; Behavioral: Pressure pain thresholds (PPT); Behavioral: Conditioned pain modulation (CPM) response; Diagnostic Test: Hormonal assessment; Other: Pubertal status

Interventions

Thermal stimuli DEVICE

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.

Also known as: Thermal Sensory Analyzer (TSA-II or PATHWAY platform - Medoc, Ramat Yishai, Israel)

Healthy control; Migraine

Pressure stimuli DEVICE

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.

Also known as: handheld algometer (Wagner Instruments), the Pressure Algometer (Medoc, Ramat Yishai, Israel)

Healthy control; Migraine

Pain ratings BEHAVIORAL

Pain intensity and pain unpleasantness ratings will be assessed.

Also known as: Numerical rating scale (ranging from 0- no pain/unpleasantness to- 100 the most intense/unpleasantness pain imaginable), mechanical and computerized visual analog scales (VAS which ranges between ''no pain sensation'' and ''most intense pain imaginable'')

Healthy control; Migraine

Pressure pain thresholds (PPT) BEHAVIORAL

Pressure will be increased continually and participants will be instructed to press a button the first moment they feel pain from the pressure stimulus. The first threshold measurement will be used as a familiarization. The average threshold is calculated from three measurements.

Healthy control; Migraine

Conditioned pain modulation (CPM) response BEHAVIORAL

The CPM paradigm assesses endogenous inhibitory pain modulation efficiency. CPM testing includes the application of a "test" stimulus without conditioning (control run, pressure pain thresholds) and a subsequent application of the same test stimulus together with a conditioning stimulus (conditioning run, a 60 second of foot immersion in cold water). The CPM response is the difference in the pressure pain thresholds between the control and the conditioning runs.

Healthy control; Migraine

PedMIDAS (Pediatric Migraine Disability Assessment) BEHAVIORAL

Adolescents with migraine will complete questions regarding their headache frequency. Migraine disability will be assessed using PedMIDAS (Pediatric Migraine Disability Assessment). This self-reported questionnaire assesses the number of days that headaches affect participant's daily activities. This is a widely used, reliable and validated tool to assess migraine disability.

Migraine

Hormonal assessment DIAGNOSTIC_TEST

Blood samples (approximetly 2 tablespoons) will be collected for analyses of sex hormone levels (e.g., testosterone, estradiol, progesterone).

Healthy control; Migraine

Pubertal status OTHER

Pubertal status will be assessed using the self-reported Physical Developmental Scale-Wave 3 survey, which allows for differentiation between pre-, early-, late-, and post-pubertal status. Early puberty is defined as a score of 3 and no menarche, mid-puberty is defined as 4 and no menarche, late pubertal is defined as a score of 7 points or less and with menarche, and post pubertal is defined as a score of 8 and menarche. For boys, pubertal maturation status will be determined by the Physical Development Scale using the body hair growth voice change and facial hair questions. Early puberty is defined as a score of 4-5, mid-puberty is defined as a score of 6-8, late pubertal is defined as a score of 9-11 points, and post pubertal is defined as a score of 12.

Healthy control; Migraine

Eligibility Criteria

• Age: 11 Years - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age between 11-15
• Males and females
• English speakers
• Migraine group: diagnosed with migraine
• Control group: Healthy, with no first degree relative with migraine

You may not qualify if:

• Pregnancy or breastfeeding,
• Chronic pain (except for migraine for the migraine group), neurological or psychiatric syndromes or syndromes associated with pubertal maturation
• Use of medications that impact sex hormone levels (i.e., contraceptive pills)

Sponsors & Collaborators

• Washington University School of Medicine: lead
• International Headache Society: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Migraine Disorders; Pain

Interventions

carboxypeptidase M

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Hadas Nahman-Averbuch, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: February 21, 2023
• Study Start: January 10, 2023
• Primary Completion: July 14, 2025
• Study Completion (Estimated): January 1, 2028
• Last Updated: October 16, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)