Hypersensitivity to PACAP-38 in Post-Traumatic Headache

Not Applicable

• Conditions: Post-Traumatic Headache
• Interventions: Drug: Pituitary adenylate cyclase activating polypeptide-38; Drug: Placebo

• Registration Number: NCT05378061
• Lead Sponsor: Danish Headache Center

Brief Summary

The aim is to investigate whether signaling molecule PACAP-38 induces headache with migraine-like features in people with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-12
• Study First Submitted QC: 2022-05-12
• Study First Posted: 2022-05-17
• Status Verified: 2022-06
• Study Start: 2022-06-16
• Last Update Submitted: 2022-06-18
• Last Update Posted: 2022-06-22
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• Age 18 to 65 years of age upon entry into screening
• History of persistent headache attributed to mild traumatic injury to the head for ≥ 12 months and in accordance with the International Classification of Headache Disorders, 3rd Edition (ICHD-3)
• ≥ 4 monthly headache days on average across the 3 months prior to screening
• Provision of informed consent prior to initiation of any study-specific activities/procedures.

Exclusion Criteria

• > 1 mild traumatic injury to the head
• History of any primary or secondary headache disorder prior to mild traumatic injury to the head (except for infrequent episodic tension-type headache)
• History of moderate or severe injury to the head
• History of whiplash injury
• History of craniotomy
• History or evidence of any other clinically significant disorder, condition or disease (except for those outlined above) than, in the opinion of the site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion
• The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior
• Female subjects of childbearing potential with a positive pregnancy test during any study visit
• Cardiovascular disease of any kind, including cerebrovascular diseases
• Hypertension (systolic blood pressure of ≥150 mmHg and/or diastolic blood pressure of ≥100 mmHg) prior to the start of infusion on the experimental day
• Hypotension (systolic blood pressure of ≤90 mmHg and/or diastolic blood pressure of ≤50 mmHg)
• Initiation, discontinuation, or change of dosing of prophylactic medications within 2 months prior to study inclusion
• Intake of acute medications (e.g. analgesics, triptans) within 48 hours of infusion start
• Baseline headache intensity of >3 on an 11-point numeric rating scale (0 being no headache, 10 being the worst imaginable headache)
• Baseline headache with migraine-like features or self-reported baseline headache that mimics the subjects' usual headache with migraine-like features

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
PACAP-38	Pituitary adenylate cyclase activating polypeptide-38	A time- and volume-controlled infusion pump is used to administer PACAP-38 by intravenous infusion over 20 minutes.
Placebo (isotonic saline)	Placebo	A time- and volume-controlled infusion pump is used to administer placebo (isotonic saline) by intravenous infusion over 20 minutes.

Primary Outcome Measures

Name	Time	Method
Incidence of Migraine-Like Headache	12 Hours	Difference in incidence of headache with migraine-like features (0 to 12 hours) between PACAP-38 and placebo.

Secondary Outcome Measures

Name	Time	Method
Headache Intensity Scores	12 Hours	Difference in area under the curve (AUC) for headache intensity scores (0 to 12 hours) between PACAP-38 and placebo.

Trial Locations

Locations (1)

Danish Headache Center; 🇩🇰 Copenhagen, Denmark