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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
Sponsored by
The University of Texas Health Science Center, Houston
About
Eligibility
Locations
Arms
Outcomes
Full info

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

Experimental

Experimental

Sham Comparator

Experimental

Experimental

Experimental

Sham Comparator

Experimental

Experimental

Experimental

Sham Comparator

Experimental

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

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
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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
No
Product Manufactured in and Exported from the U.S.
No
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
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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