Pain Biomarker Study

NCT03511846 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 1 other identifier: HSC-MS-17-0763
• Study Type: interventional
• Target: 371
• Locations: 1 country
• Sites: 1

Brief 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. 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 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.
2. 2.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.
3. 3.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; Short-Lasting Unilateral Neuralgiform Headache With Conjunctival Injection and Tearing

Keywords

Brain Freeze; Capsaicin

Outcome Measures

Primary Outcomes (2)

• Activation of trigeminoautonomic reflex as assessed by change in Calcitonin gene-related peptide (CGRP) levels from before stimulation to after stimulation.

  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

  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.

  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

  90 minutes after pain stimulation

• Activation of trigeminoautonomic reflex as assessed by nasal fluid production

  90 minutes after pain stimulation

• Activation of trigeminoautonomic reflex as assessed by tactile threshold measurement with von Frey Filaments

  90 minutes after pain stimulation

• Activation of trigeminoautonomic reflex as assessed by dermal blood flow

  90 minutes after pain stimulation

Study Arms (16)

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

Interventions

Oral capsaicin DRUG

Subjects will drink a solution with capsaicin

Oral Capsaicin and Low Flow Oxygen; Oral capsaicin; Oral capsaicin and High Flow Oxygen; Oral capsaicin and Medical Air

Topical capsaicin DRUG

Capsaicin cream will be applied to the skin of the forehead, cheek, or leg

Topical capsaicin; Topical capsaicin and High Flow Oxygen; Topical capsaicin and Low Flow Oxygen; Topical capsaicin and Medical Air

Intranasal capsaicin DRUG

Capsaicin cream will be applied to the nostril

Intranasal capsaicin; Intranasal capsaicin and High Flow Oxygen; Intranasal capsaicin and Low Flow Oxygen; Intranasal capsaicin and Medical Air

Cold Water Irrigation OTHER

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)

Cold water irrigation; Cold water irrigation and High Flow Oxygen; Cold water irrigation and Low Flow Oxygen; Cold water irrigation and Medical Air

Medical Air OTHER

Subjects will be exposed to medical air

Cold water irrigation and Medical Air; Intranasal capsaicin and Medical Air; Oral capsaicin and Medical Air; Topical capsaicin and Medical Air

Low Flow Oxygen DRUG

Subjects will be exposed to oxygen gas between 1-9 L/min

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 Oxygen DRUG

Subjects will be exposed to oxygen gas between 10-25 L/min

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• University of California, San Francisco: collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Migraine Disorders; Cluster Headache; Trigeminal Autonomic Cephalalgias; Paroxysmal Hemicrania; Lacerations

Interventions

Capsaicin; Air

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Polyunsaturated Alkamides; Amides; Organic Chemicals; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Atmosphere; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Meteorological Concepts; Environment and Public Health

Study Officials

• Mark Burish, MD PhD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: In the oxygen portion of the study, subjects and the outcomes assessors will be told that they will be receiving either medical air or oxygen.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 17, 2018
• First Posted: April 30, 2018
• Study Start: March 21, 2018
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2028
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

US (1)