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Pain Biomarker Study (PBS)

Primary Purpose

Migraine, Cluster Headache, Trigeminal Autonomic Cephalgia

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Oral capsaicin

Topical capsaicin

Intranasal capsaicin

Cold Water Irrigation

Medical Air

Low Flow Oxygen

High Flow Oxygen

About this trial

This is an interventional basic science trial for Migraine focused on measuring Brain Freeze, Capsaicin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

The University of Texas Health Science Center at Houston

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm Type

Experimental

Sham Comparator

Experimental

Sham Comparator

Experimental

Sham Comparator

Experimental

Sham Comparator

Experimental

Arm Label

Oral capsaicin

Oral capsaicin and Medical Air

Oral Capsaicin and Low Flow Oxygen

Oral capsaicin and High Flow Oxygen

Topical capsaicin

Topical capsaicin and Medical Air

Topical capsaicin and Low Flow Oxygen

Topical capsaicin and High Flow Oxygen

Intranasal capsaicin

Intranasal capsaicin and Medical Air

Intranasal capsaicin and Low Flow Oxygen

Intranasal capsaicin and High Flow Oxygen

Cold water irrigation

Cold water irrigation and Medical Air

Cold water irrigation and Low Flow Oxygen

Cold water irrigation and High Flow Oxygen

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Activation of trigeminoautonomic reflex as assessed by saliva production

Activation of trigeminoautonomic reflex as assessed by nasal fluid production

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

Activation of trigeminoautonomic reflex as assessed by dermal blood flow

Full Information

NCT ID

NCT03511846

First Posted

April 17, 2018

Last Updated

October 31, 2022

Sponsor

The University of Texas Health Science Center, Houston

Collaborators

University of California, San Francisco

1. Study Identification

Unique Protocol Identification Number

NCT03511846

Brief Title

Pain Biomarker Study

Acronym

PBS

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 21, 2018 (Actual)

Primary Completion Date

May 31, 2024 (Anticipated)

Study Completion Date

May 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The University of Texas Health Science Center, Houston

Collaborators

University of California, San Francisco

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Masking Description

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.

Allocation

Non-Randomized

Enrollment

371 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Oral capsaicin

Arm Type

Experimental

Arm Title

Oral capsaicin and Medical Air

Arm Type

Sham Comparator

Arm Title

Oral Capsaicin and Low Flow Oxygen

Arm Type

Experimental

Arm Title

Oral capsaicin and High Flow Oxygen

Arm Type

Experimental

Arm Title

Topical capsaicin

Arm Type

Experimental

Arm Title

Topical capsaicin and Medical Air

Arm Type

Sham Comparator

Arm Title

Topical capsaicin and Low Flow Oxygen

Arm Type

Experimental

Arm Title

Topical capsaicin and High Flow Oxygen

Arm Type

Experimental

Arm Title

Intranasal capsaicin

Arm Type

Experimental

Arm Title

Intranasal capsaicin and Medical Air

Arm Type

Sham Comparator

Arm Title

Intranasal capsaicin and Low Flow Oxygen

Arm Type

Experimental

Arm Title

Intranasal capsaicin and High Flow Oxygen

Arm Type

Experimental

Arm Title

Cold water irrigation

Arm Type

Experimental

Arm Title

Cold water irrigation and Medical Air

Arm Type

Sham Comparator

Arm Title

Cold water irrigation and Low Flow Oxygen

Arm Type

Experimental

Arm Title

Cold water irrigation and High Flow Oxygen

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Oral capsaicin

Intervention Description

Subjects will drink a solution with capsaicin

Intervention Type

Drug

Intervention Name(s)

Topical capsaicin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Intranasal capsaicin

Intervention Description

Capsaicin cream will be applied to the nostril

Intervention Type

Other

Intervention Name(s)

Cold Water Irrigation

Intervention Description

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

Intervention Name(s)

Medical Air

Intervention Description

Subjects will be exposed to medical air

Intervention Type

Drug

Intervention Name(s)

Low Flow Oxygen

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

High Flow Oxygen

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Title

Activation of trigeminoautonomic reflex as assessed by tear fluid production

Description

The amount of tear fluid after each intervention will be measured via Schirmer strips

Time Frame

90 minutes after pain stimulation

Secondary Outcome Measure Information:

Title

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

Title

Activation of trigeminoautonomic reflex as assessed by saliva production

Time Frame

90 minutes after pain stimulation

Title

Activation of trigeminoautonomic reflex as assessed by nasal fluid production

Time Frame

90 minutes after pain stimulation

Title

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

Time Frame

90 minutes after pain stimulation

Title

Activation of trigeminoautonomic reflex as assessed by dermal blood flow

Time Frame

90 minutes after pain stimulation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark Burish, MD PhD

Organizational Affiliation

The University of Texas Health Science Center, Houston

Official's Role

Principal Investigator

Facility Information:

Facility Name

The University of Texas Health Science Center at Houston

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Pain Biomarker Study

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