MigrainePhase 1PBSNCT03511846

Pain Biomarker Study

A Phase 1 study testing Oral capsaicin, Topical capsaicin and Intranasal capsaicin in people with Migraine and Cluster Headache, run by The University of Texas Health Science Center, Houston at 1 site in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts

Official record

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Trial summary

This study investigates molecular and physical biomarkers of headaches in order to better understand mechanisms of these diseases. There are 3 main parts: 1. Use of capsaicin (active ingredient in hot chili peppers) to trigger release of calcitonin gene related peptide - the hypothesis is that this will be different… Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Migraine, Cluster Headache, Trigeminal Autonomic Cephalgia
What is being tested?: Oral capsaicin, Topical capsaicin and Intranasal capsaicin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 371 participants
Where: 1 siteUnited States
Study dates: 21 Mar 2018to 31 May 2028
Phase: Phase 1
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 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Diagnosis of one of the following: a. Diagnosis of a primary headache disorder according to the International Headache Classification, including migraine with aura, migraine without aura, chronic migraine, tension headache, cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA), and hemicrania continua; b. Diagnosed by a pain medicine physician with lumbar radiculopathy (possibly including neuropathic features, nerve impingement on MRI, or electromyography (EMG) report suggestive of lumbar radiculopathy); or c. Healthy control subject with no history of debilitating headaches or debilitating back pain / radiculopathy pain, and no headaches or back pain within the previous 3 months.
Able to provide HIPAA authorization to share prior medical records/imaging
Age 18 and older

Who cannot join

The following items exclude the subject from all portions of the study: a. Known history of cardiovascular or neurovascular diseases. These diseases may include carotid stenosis of >50%, vertebral stenosis, peripheral vascular disease, angina or myocardial infarction, stroke, or vascular malformations; b. History of brain tumors or epilepsy; c. Active pregnancy or lactation; d. Daily cigarette, tobacco or nicotine use; e. Life expectancy less than 1 year, co-existing disease or other characteristic that precludes appropriate diagnosis of headache or spine pain; f. Active drug / alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements; or g. Inability or unwillingness of subject to give informed consent (e.g., ward of the state)
The following items exclude the subject only from the capsaicin portion of the study: a. Known allergy to capsaicin or hot peppers
The following items exclude the subject only from the oxygen portion of the study: a. Pulmonary or other non-headache diseases that require the use of supplemental oxygen
The following items exclude the subject only from the cold water irrigation (ice water) portion of the study: a. Trauma, fractures, or congenital abnormalities of the soft palate

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site

The University of Texas Health Science Center at Houston
Houston, Texas, 77030

Other trials in United States

About this study

Official title: The Pain Biomarker Study: Changes in Circulating Pain Signalling Molecules With Activation of Pain Receptors

This study investigates molecular and physical biomarkers of headaches in order to better understand mechanisms of these diseases.

There are 3 main parts:

Use of capsaicin (active ingredient in hot chili peppers) to trigger release of calcitonin gene related peptide - the hypothesis is that this will be different in headache subjects compared to controls (and if so might be used to predict how these patients will respond to certain medications that modulate calcitonin gene-related peptide). Subjects will be given capsaicin as a cream applied to the forehead or the inner nostril, or a hot sauce that is ingested.
Use of capsaicin to trigger eye watering - the hypothesis is that oxygen gas will slow down the amount of eye watering. Cluster headache patients respond very powerfully to oxygen gas but to very little else. The mechanism for oxygen is unknown but in rodents there is data that it works on the parasympathetic / lacrimal gland system. This study translates rodent data into humans in a non-invasive way to confirm the mechanism of this very effective treatment.
Use of ice water to trigger headaches - brain freeze causes a very short-lived but intense headache that may cause similar biomarker release as other headache disorders. This may be a useful human model for other headache disorders.

Conditions: Migraine, Cluster Headache, Trigeminal Autonomic Cephalgia, Hemicrania Continua, Paroxysmal Hemicrania, SUNCT
Being tested: Oral capsaicin, Topical capsaicin, Intranasal capsaicin, Cold Water Irrigation, Medical Air
Keywords: Brain Freeze, Capsaicin
Medical subject headings: Migraine Disorders, Cluster Headache, Trigeminal Autonomic Cephalalgias, Paroxysmal Hemicrania, Lacerations

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Oral capsaicinDrug
Subjects will drink a solution with capsaicin
Topical capsaicinDrug
Capsaicin cream will be applied to the skin of the forehead, cheek, or leg
Intranasal capsaicinDrug
Capsaicin cream will be applied to the nostril
Cold Water IrrigationOther
Subjects will be asked to drink up to 2000 ml of cold water or ice water (temperature 0-10 degrees Celsius) as fast as possible, either continuously or intermittently (i.e. 200-800 ml at a time)
Medical AirOther
Subjects will be exposed to medical air
Low Flow OxygenDrug
Subjects will be exposed to oxygen gas between 1-9 L/min
High Flow OxygenDrug
Subjects will be exposed to oxygen gas between 10-25 L/min

Study groups in NCT03511846
Study group	Role	What they receive
Oral capsaicin	Experimental	Not described Receives: Drug: Oral capsaicin
Oral capsaicin and Medical Air	Sham comparator	Not described Receives: Drug: Oral capsaicin; Other: Medical Air
Oral Capsaicin and Low Flow Oxygen	Experimental	Not described Receives: Drug: Oral capsaicin; Drug: Low Flow Oxygen
Oral capsaicin and High Flow Oxygen	Experimental	Not described Receives: Drug: Oral capsaicin; Drug: High Flow Oxygen
Topical capsaicin	Experimental	Not described Receives: Drug: Topical capsaicin
Topical capsaicin and Medical Air	Sham comparator	Not described Receives: Drug: Topical capsaicin; Other: Medical Air
Topical capsaicin and Low Flow Oxygen	Experimental	Not described Receives: Drug: Topical capsaicin; Drug: Low Flow Oxygen
Topical capsaicin and High Flow Oxygen	Experimental	Not described Receives: Drug: Topical capsaicin; Drug: High Flow Oxygen
Intranasal capsaicin	Experimental	Not described Receives: Drug: Intranasal capsaicin
Intranasal capsaicin and Medical Air	Sham comparator	Not described Receives: Drug: Intranasal capsaicin; Other: Medical Air
Intranasal capsaicin and Low Flow Oxygen	Experimental	Not described Receives: Drug: Intranasal capsaicin; Drug: Low Flow Oxygen
Intranasal capsaicin and High Flow Oxygen	Experimental	Not described Receives: Drug: Intranasal capsaicin; Drug: High Flow Oxygen
Cold water irrigation	Experimental	Not described Receives: Other: Cold Water Irrigation
Cold water irrigation and Medical Air	Sham comparator	Not described Receives: Other: Cold Water Irrigation; Other: Medical Air
Cold water irrigation and Low Flow Oxygen	Experimental	Not described Receives: Other: Cold Water Irrigation; Drug: Low Flow Oxygen
Cold water irrigation and High Flow Oxygen	Experimental	Not described Receives: Other: Cold Water Irrigation; Drug: High Flow Oxygen

What is being measured

The primary outcome is the main question the study is designed to answer.

Activation of trigeminoautonomic reflex as assessed by change in Calcitonin gene-related peptide (CGRP) levels from before stimulation to after stimulation.
Measured: 10 minutes before pain stimulation and 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by tear fluid production
The amount of tear fluid after each intervention will be measured via Schirmer strips
Measured: 90 minutes after pain stimulation

Secondary outcomes (5)

Activation of trigeminoautonomic reflex as assessed by change in pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) levels levels from before stimulation to after stimulation.
Measured: 10 minutes before pain stimulation and 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by saliva production
Measured: 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by nasal fluid production
Measured: 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by tactile threshold measurement with von Frey Filaments
Measured: 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by dermal blood flow
Measured: 90 minutes after pain stimulation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Mar 201831 May 2028

First posted30 Apr 2018
Study start21 Mar 2018
Primary completion31 May 2028 (estimated)
Study completion31 May 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.
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 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 371 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03511846
Sponsor's protocol ID: HSC-MS-17-0763
Acronym: PBS
Status last verified: Feb 2026
First submitted: 17 Apr 2018
Last updated: 18 Feb 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Interested in taking part?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

RecruitingPhase 2/3
Efficacy and Safety of BR005-036C Tablets for the Acute Treatment of Migraine in Adults
Migraine, With or Without Aura
Not yet recruiting
Laser Acupuncture for Chronic Migraine: Clinical Response, Traditional Chinese Medicine Syndrome Patterns, and Brain Function
Chronic Migraine Headache
Active, not recruitingPhase 3
A Study to Learn About the Study Medicine Called Rimegepant in Adolescents With Frequent Migraine
Migraine
Not yet recruitingPhase 3
Eary Infusion of Eptinezumab for TreatmEnt of ACute Post-Traumatic Headaches (ELITE-ACT)
Post Traumatic Headache
Not yet recruitingObservational study
Validation of the Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI) for Adolescents
Vestibular Migraine

All Migraine trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Pain Biomarker Study: Changes in Circulating Pain Signalling Molecules With Activation of Pain Receptors
ClinicalTrials.gov ID: NCT03511846
Acronym / sponsor ID: PBS / HSC-MS-17-0763
Conditions: Migraine, Cluster Headache, Trigeminal Autonomic Cephalgia, Hemicrania Continua, Paroxysmal Hemicrania, SUNCT
Keywords: Brain Freeze, Capsaicin
Phase: Phase 1
Study type: Interventional
Recruitment status: Enrolling by invitation
Enrolment: 371 participants (estimated)
Lead sponsor: The University of Texas Health Science Center, HoustonUniversity, hospital or other
Collaborators: University of California, San Francisco
Study start: 21 Mar 2018 (actual)
Primary completion: 31 May 2028 (estimated)
Study completion: 31 May 2028 (estimated)
First posted: 30 Apr 2018 (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.

This study investigates molecular and physical biomarkers of headaches in order to better understand mechanisms of these diseases.

There are 3 main parts:

Use of capsaicin (active ingredient in hot chili peppers) to trigger release of calcitonin gene related peptide - the hypothesis is that this will be different in headache subjects compared to controls (and if so might be used to predict how these patients will respond to certain medications that modulate calcitonin gene-related peptide). Subjects will be given capsaicin as a cream applied to the forehead or the inner nostril, or a hot sauce that is ingested.
Use of capsaicin to trigger eye watering - the hypothesis is that oxygen gas will slow down the amount of eye watering. Cluster headache patients respond very powerfully to oxygen gas but to very little else. The mechanism for oxygen is unknown but in rodents there is data that it works on the parasympathetic / lacrimal gland system. This study translates rodent data into humans in a non-invasive way to confirm the mechanism of this very effective treatment.
Use of ice water to trigger headaches - brain freeze causes a very short-lived but intense headache that may cause similar biomarker release as other headache disorders. This may be a useful human model for other headache disorders.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 16

Arm	Type	Receives
Oral capsaicin	Experimental	Drug: Oral capsaicin
Oral capsaicin and Medical Air	Sham comparator	Drug: Oral capsaicin, Other: Medical Air
Oral Capsaicin and Low Flow Oxygen	Experimental	Drug: Oral capsaicin, Drug: Low Flow Oxygen
Oral capsaicin and High Flow Oxygen	Experimental	Drug: Oral capsaicin, Drug: High Flow Oxygen
Topical capsaicin	Experimental	Drug: Topical capsaicin
Topical capsaicin and Medical Air	Sham comparator	Drug: Topical capsaicin, Other: Medical Air
Topical capsaicin and Low Flow Oxygen	Experimental	Drug: Topical capsaicin, Drug: Low Flow Oxygen
Topical capsaicin and High Flow Oxygen	Experimental	Drug: Topical capsaicin, Drug: High Flow Oxygen
Intranasal capsaicin	Experimental	Drug: Intranasal capsaicin
Intranasal capsaicin and Medical Air	Sham comparator	Drug: Intranasal capsaicin, Other: Medical Air
Intranasal capsaicin and Low Flow Oxygen	Experimental	Drug: Intranasal capsaicin, Drug: Low Flow Oxygen
Intranasal capsaicin and High Flow Oxygen	Experimental	Drug: Intranasal capsaicin, Drug: High Flow Oxygen
Cold water irrigation	Experimental	Other: Cold Water Irrigation
Cold water irrigation and Medical Air	Sham comparator	Other: Cold Water Irrigation, Other: Medical Air
Cold water irrigation and Low Flow Oxygen	Experimental	Other: Cold Water Irrigation, Drug: Low Flow Oxygen
Cold water irrigation and High Flow Oxygen	Experimental	Other: Cold Water Irrigation, Drug: High Flow Oxygen

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Diagnosis of one of the following: a. Diagnosis of a primary headache disorder according to the International Headache Classification, including migraine with aura, migraine without aura, chronic migraine, tension headache, cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA), and hemicrania continua; b. Diagnosed by a pain medicine physician with lumbar radiculopathy (possibly including neuropathic features, nerve impingement on MRI, or electromyography (EMG) report suggestive of lumbar radiculopathy); or c. Healthy control subject with no history of debilitating headaches or debilitating back pain / radiculopathy pain, and no headaches or back pain within the previous 3 months.
Able to provide HIPAA authorization to share prior medical records/imaging
Age 18 and older

Key exclusion criteria (4 listed)

The following items exclude the subject from all portions of the study: a. Known history of cardiovascular or neurovascular diseases. These diseases may include carotid stenosis of >50%, vertebral stenosis, peripheral vascular disease, angina or myocardial infarction, stroke, or vascular malformations; b. History of brain tumors or epilepsy; c. Active pregnancy or lactation; d. Daily cigarette, tobacco or nicotine use; e. Life expectancy less than 1 year, co-existing disease or other characteristic that precludes appropriate diagnosis of headache or spine pain; f. Active drug / alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements; or g. Inability or unwillingness of subject to give informed consent (e.g., ward of the state)
The following items exclude the subject only from the capsaicin portion of the study: a. Known allergy to capsaicin or hot peppers
The following items exclude the subject only from the oxygen portion of the study: a. Pulmonary or other non-headache diseases that require the use of supplemental oxygen
The following items exclude the subject only from the cold water irrigation (ice water) portion of the study: a. Trauma, fractures, or congenital abnormalities of the soft palate

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
Oral capsaicinSubjects will drink a solution with capsaicin	Drug	Oral Capsaicin and Low Flow Oxygen, Oral capsaicin, Oral capsaicin and High Flow Oxygen, Oral capsaicin and Medical Air
Topical capsaicinCapsaicin cream will be applied to the skin of the forehead, cheek, or leg	Drug	Topical capsaicin, Topical capsaicin and High Flow Oxygen, Topical capsaicin and Low Flow Oxygen, Topical capsaicin and Medical Air
Intranasal capsaicinCapsaicin cream will be applied to the nostril	Drug	Intranasal capsaicin, Intranasal capsaicin and High Flow Oxygen, Intranasal capsaicin and Low Flow Oxygen, Intranasal capsaicin and Medical Air
Cold Water IrrigationSubjects will be asked to drink up to 2000 ml of cold water or ice water (temperature 0-10 degrees Celsius) as fast as possible, either continuously or intermittently (i.e. 200-800 ml at a time)	Other	Cold water irrigation, Cold water irrigation and High Flow Oxygen, Cold water irrigation and Low Flow Oxygen, Cold water irrigation and Medical Air
Medical AirSubjects will be exposed to medical air	Other	Cold water irrigation and Medical Air, Intranasal capsaicin and Medical Air, Oral capsaicin and Medical Air, Topical capsaicin and Medical Air
Low Flow OxygenSubjects will be exposed to oxygen gas between 1-9 L/min	Drug	Cold water irrigation and Low Flow Oxygen, Intranasal capsaicin and Low Flow Oxygen, Oral Capsaicin and Low Flow Oxygen, Topical capsaicin and Low Flow Oxygen
High Flow OxygenSubjects will be exposed to oxygen gas between 10-25 L/min	Drug	Cold water irrigation and High Flow Oxygen, Intranasal capsaicin and High Flow Oxygen, Oral capsaicin and High Flow Oxygen, Topical capsaicin and High Flow Oxygen

Primary outcome

Activation of trigeminoautonomic reflex as assessed by change in Calcitonin gene-related peptide (CGRP) levels from before stimulation to after stimulation.
Time frame: 10 minutes before pain stimulation and 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by tear fluid production
Time frame: 90 minutes after pain stimulation
The amount of tear fluid after each intervention will be measured via Schirmer strips

5 secondary outcomes

Activation of trigeminoautonomic reflex as assessed by change in pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) levels levels from before stimulation to after stimulation.
Time frame: 10 minutes before pain stimulation and 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by saliva production
Time frame: 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by nasal fluid production
Time frame: 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by tactile threshold measurement with von Frey Filaments
Time frame: 90 minutes after pain stimulation
Activation of trigeminoautonomic reflex as assessed by dermal blood flow
Time frame: 90 minutes after pain stimulation

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 18 Feb 2026.
Individual participant dataSharing planned: Undecided

Related trials for Migraine

RecruitingPhase 2/3
Efficacy and Safety of BR005-036C Tablets for the Acute Treatment of Migraine in Adults
Migraine, With or Without Aura
Not yet recruiting
Laser Acupuncture for Chronic Migraine: Clinical Response, Traditional Chinese Medicine Syndrome Patterns, and Brain Function
Chronic Migraine Headache
Active, not recruitingPhase 3
A Study to Learn About the Study Medicine Called Rimegepant in Adolescents With Frequent Migraine
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Not yet recruitingPhase 3
Eary Infusion of Eptinezumab for TreatmEnt of ACute Post-Traumatic Headaches (ELITE-ACT)
Post Traumatic Headache
Not yet recruitingObservational study
Validation of the Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI) for Adolescents
Vestibular Migraine

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.

Mark Burish, MD PhD principal investigator

The University of Texas Health Science Center, Houston

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 3 inclusion and 4 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: enrolling by invitation, as of the sponsor's last update on 18 Feb 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.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Activation of trigeminoautonomic reflex as assessed by change in Calcitonin gene-related peptide (CGRP) levels from before stimulation to after stimulation. (time frame: 10 minutes before pain stimulation and 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 90 minutes after pain stimulation). 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?

On the ClinicalTrials.gov record for NCT03511846.

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 18 Feb 2026.