MigraineIHSNCT05738213
Puberty, Sex Hormones and Pain Sensitivity in Adolescents With Migraine
A study testing Thermal stimuli, Pressure stimuli and Pain ratings in people with Migraine, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 11 to 15 yearsHealthy volunteers can take part
- Conditions the study is for
- Migraine
- What is being tested?
- Thermal stimuli, Pressure stimuli and Pain ratings
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2023to 1 Jan 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 11 to 15 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Age between 11-15
- Males and females
- English speakers
- Migraine group: diagnosed with migraine
- Control group: Healthy, with no first degree relative with migraine
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Hormonal Effects of Puberty-Related Alterations on Pain in Adolescents With Migraine
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.
Read the detailed description
This study will investigate how puberty and variability in sex hormone levels impact pain sensitivity and migraine symptoms.
Hypothesis 1- A significant reduction in pain sensitivity from early to late pubertal status will be found only for adolescents without but not with migraine during pubertal maturation.
Hypothesis 2- Experimental pain sensitivity will be negatively correlated with testosterone levels in adolescents in both groups (with and without migraine).
Exploratory Hypothesis 1- In adolescents with migraine, higher migraine severity (headache frequency and migraine disability) will be associated with lower testosterone levels.
Exploratory hypothesis 2- Adolescents with migraine will have lower testosterone levels than those without.
- Conditions
- Migraine
- Being tested
- Thermal stimuli, Pressure stimuli, Pain ratings, Pressure pain thresholds (PPT), Conditioned pain modulation (CPM) response
- Keywords
- pain, puberty, sex hormones
- Medical subject headings
- Migraine Disorders, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thermal stimuliDevice
Also called Thermal Sensory Analyzer (TSA-II or PATHWAY platform - Medoc, Ramat Yishai, Israel)
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.
Pressure stimuliDevice
Also called handheld algometer (Wagner Instruments), the Pressure Algometer (Medoc, Ramat Yishai, Israel)
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.
Pain ratingsBehavioural
Also called 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'')
Pain intensity and pain unpleasantness ratings will be assessed.
Pressure pain thresholds (PPT)Behavioural
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.
Conditioned pain modulation (CPM) responseBehavioural
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.
PedMIDAS (Pediatric Migraine Disability Assessment)Behavioural
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.
Hormonal assessmentDiagnostic test
Blood samples (approximetly 2 tablespoons) will be collected for analyses of sex hormone levels (e.g., testosterone, estradiol, progesterone).
Pubertal statusOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Migraine | Active comparator | Adolescents with a migraine diagnosis Receives: 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 Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline
Sex Hormones
Testosterone levels
Measured: Baseline
Secondary outcomes (2)
Sex hormone assessments
Estrogen levels
Measured: Baseline
Migraine specific measures
Pediatric Migraine Disability Assessment (PedMIDAS) (range 0-540, higher values indicate more disability, with scores >50 considered as severe disability)
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study start10 Jan 2023
- Primary completion14 Jul 2025
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MigraineStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- International Headache Society
- Responsible party
- Principal investigator, Hadas Nahman-Averbuch, Washington University School of Medicine
- Investigators
- Hadas Nahman-Averbuch, PhD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05738213
- Sponsor's protocol ID
- 202208057
- Other IDs
- Seed Pediatric Research Grant
- Acronym
- IHS
- Status last verified
- Jul 2026
- First submitted
- 6 Dec 2022
- Last updated
- 13 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hormonal Effects of Puberty-Related Alterations on Pain in Adolescents With Migraine
- ClinicalTrials.gov ID
- NCT05738213
- Acronym / sponsor ID
- IHS / 202208057
- Conditions
- Migraine
- Keywords
- pain, puberty, sex hormones
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- International Headache Society
- Study start
- 10 Jan 2023 (actual)
- Primary completion
- 14 Jul 2025 (actual)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 21 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study will investigate how puberty and variability in sex hormone levels impact pain sensitivity and migraine symptoms.
Hypothesis 1- A significant reduction in pain sensitivity from early to late pubertal status will be found only for adolescents without but not with migraine during pubertal maturation.
Hypothesis 2- Experimental pain sensitivity will be negatively correlated with testosterone levels in adolescents in both groups (with and without migraine).
Exploratory Hypothesis 1- In adolescents with migraine, higher migraine severity (headache frequency and migraine disability) will be associated with lower testosterone levels.
Exploratory hypothesis 2- Adolescents with migraine will have lower testosterone levels than those without.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Migraine | Active comparator | 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 statusAdolescents with a migraine diagnosis |
| Healthy control | Placebo comparator | 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 statusAdolescents without a migraine diagnosis |
Who may qualify
- Ages
- 11 to 15 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Age between 11-15
- Males and females
- English speakers
- Migraine group: diagnosed with migraine
- Control group: Healthy, with no first degree relative with migraine
Key exclusion criteria (3 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thermal stimuliAlso: Thermal Sensory Analyzer (TSA-II or PATHWAY platform - Medoc, Ramat Yishai, Israel)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. | Device | Healthy control, Migraine |
| Pressure stimuliAlso: handheld algometer (Wagner Instruments), the Pressure Algometer (Medoc, Ramat Yishai, Israel)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. | Device | Healthy control, Migraine |
| Pain ratingsAlso: 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'')Pain intensity and pain unpleasantness ratings will be assessed. | Behavioural | Healthy control, Migraine |
| Pressure pain thresholds (PPT)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. | Behavioural | Healthy control, Migraine |
| Conditioned pain modulation (CPM) responseThe 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. | Behavioural | Healthy control, Migraine |
| PedMIDAS (Pediatric Migraine Disability Assessment)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. | Behavioural | Migraine |
| Hormonal assessmentBlood samples (approximetly 2 tablespoons) will be collected for analyses of sex hormone levels (e.g., testosterone, estradiol, progesterone). | Diagnostic test | Healthy control, Migraine |
| Pubertal statusPubertal 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. | Other | Healthy control, Migraine |
Primary outcome
Conditioned pain modulation (CPM) response
Time frame: Baseline
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.
Sex Hormones
Time frame: Baseline
Testosterone levels
2 secondary outcomes
Sex hormone assessments
Time frame: Baseline
Migraine specific measures
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hadas Nahman-Averbuch, PhD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Thermal stimuli, Pressure stimuli and Pain ratings in people with Migraine, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conditioned pain modulation (CPM) response (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026.