Clinical trial NCT03511846: Pain Biomarker Study
Official title: The Pain Biomarker Study: Changes in Circulating Pain Signalling Molecules with Activation of Pain Receptors
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
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
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
First posted: 2018-04-30
Enrollment: 371
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Activation of trigeminoautonomic reflex as assessed by change in Calcitonin gene-related peptide (CGRP) levels from before stimulation to after stimulation.
timeFrame: 10 minutes before pain stimulation and 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 90 minutes after pain stimulation
measure: Activation of trigeminoautonomic reflex as assessed by tear fluid production
timeFrame: 90 minutes after pain stimulation
Secondary outcomes:
measure: 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.
timeFrame: 10 minutes before pain stimulation and 10 minutes, 20 minutes, 30 minutes, 60 minutes, and 90 minutes after pain stimulation
measure: Activation of trigeminoautonomic reflex as assessed by saliva production
timeFrame: 90 minutes after pain stimulation
measure: Activation of trigeminoautonomic reflex as assessed by nasal fluid production
timeFrame: 90 minutes after pain stimulation
measure: Activation of trigeminoautonomic reflex as assessed by tactile threshold measurement with von Frey Filaments
timeFrame: 90 minutes after pain stimulation
measure: Activation of trigeminoautonomic reflex as assessed by dermal blood flow
timeFrame: 90 minutes after pain stimulation
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Mark Burish, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: