Pain Biomarker Study

NCT ID: NCT03511846

Last Updated: 2025-01-14

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE1
• Total Enrollment: 371 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-21
• Study Completion Date: 2026-05-31

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. 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. 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. 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Oral capsaicin

Group Type: EXPERIMENTAL

Oral capsaicin

Intervention Type: DRUG

Subjects will drink a solution with capsaicin

Oral capsaicin and Medical Air

Group Type: SHAM_COMPARATOR

Oral capsaicin

Intervention Type: DRUG

Subjects will drink a solution with capsaicin

Medical Air

Intervention Type: OTHER

Subjects will be exposed to medical air

Oral Capsaicin and Low Flow Oxygen

Group Type: EXPERIMENTAL

Oral capsaicin

Intervention Type: DRUG

Subjects will drink a solution with capsaicin

Low Flow Oxygen

Intervention Type: DRUG

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

Oral capsaicin and High Flow Oxygen

Group Type: EXPERIMENTAL

Oral capsaicin

Intervention Type: DRUG

Subjects will drink a solution with capsaicin

High Flow Oxygen

Intervention Type: DRUG

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

Topical capsaicin

Group Type: EXPERIMENTAL

Topical capsaicin

Intervention Type: DRUG

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

Topical capsaicin and Medical Air

Group Type: SHAM_COMPARATOR

Topical capsaicin

Intervention Type: DRUG

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

Medical Air

Intervention Type: OTHER

Subjects will be exposed to medical air

Topical capsaicin and Low Flow Oxygen

Group Type: EXPERIMENTAL

Topical capsaicin

Intervention Type: DRUG

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

Low Flow Oxygen

Intervention Type: DRUG

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

Topical capsaicin and High Flow Oxygen

Group Type: EXPERIMENTAL

Topical capsaicin

Intervention Type: DRUG

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

High Flow Oxygen

Intervention Type: DRUG

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

Intranasal capsaicin

Group Type: EXPERIMENTAL

Intranasal capsaicin

Intervention Type: DRUG

Capsaicin cream will be applied to the nostril

Intranasal capsaicin and Medical Air

Group Type: SHAM_COMPARATOR

Intranasal capsaicin

Intervention Type: DRUG

Capsaicin cream will be applied to the nostril

Medical Air

Intervention Type: OTHER

Subjects will be exposed to medical air

Intranasal capsaicin and Low Flow Oxygen

Group Type: EXPERIMENTAL

Intranasal capsaicin

Intervention Type: DRUG

Capsaicin cream will be applied to the nostril

Low Flow Oxygen

Intervention Type: DRUG

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

Intranasal capsaicin and High Flow Oxygen

Group Type: EXPERIMENTAL

Intranasal capsaicin

Intervention Type: DRUG

Capsaicin cream will be applied to the nostril

High Flow Oxygen

Intervention Type: DRUG

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

Cold water irrigation

Group Type: EXPERIMENTAL

Cold Water Irrigation

Intervention Type: 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 and Medical Air

Group Type: SHAM_COMPARATOR

Cold Water Irrigation

Intervention Type: 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)

Medical Air

Intervention Type: OTHER

Subjects will be exposed to medical air

Cold water irrigation and Low Flow Oxygen

Group Type: EXPERIMENTAL

Cold Water Irrigation

Intervention Type: 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)

Low Flow Oxygen

Intervention Type: DRUG

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

Cold water irrigation and High Flow Oxygen

Group Type: EXPERIMENTAL

Cold Water Irrigation

Intervention Type: 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)

High Flow Oxygen

Intervention Type: DRUG

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

Interventions

Oral capsaicin

Subjects will drink a solution with capsaicin

Intervention Type: DRUG

Topical capsaicin

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

Intervention Type: DRUG

Intranasal capsaicin

Capsaicin cream will be applied to the nostril

Intervention Type: DRUG

Cold Water Irrigation

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)

Intervention Type: OTHER

Medical Air

Subjects will be exposed to medical air

Intervention Type: OTHER

Low Flow Oxygen

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

Intervention Type: DRUG

High Flow Oxygen

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Mark J Burish

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Burish, MD PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Countries

United States

Other Identifiers

HSC-MS-17-0763

Identifier Type: -

Identifier Source: org_study_id