Clinical Characteristics and Pathophysiology of Post-Traumatic Headache

NCT ID: NCT03791515

Last Updated: 2020-01-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-26

Study Completion Date

2019-12-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

To better understand the clinical characteristics and complex pathophysiological events that constitute persistent post-traumatic headache (PPTH) and to identify possible calcitonin gene-related peptide (CGRP) hypersensitivity in PPTH patients.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The present project will embark upon identifying novel PTH-specific biomarkers by incorporating a plethora of scientific approaches. First, clinical biomarkers will be assessed by deep phenotyping of clinical characteristics and associated comorbidities using a semi-structured interview and multiple validated questionnaires. Second, biochemical biomarkers will be determined by plasma levels measurements of blood markers for headache hypersensitivity and neuronal/axonal damage. Third, imaging biomarkers will be established by magnetic resonance imaging (MRI) to assess structural and functional changes in the brain. Lastly, molecular biomarkers will be identified by examining whether intravenous infusion of calcitonin gene-related peptide (CGRP) provokes headache attacks mimicking the usual headache phenotype in subjects with PTH. This would determine whether PTH patients exhibit hypersensitivity to CGRP (molecular biomarker) and advance our understanding of the complex pathophysiological events that constitute the headache phenotypes in PTH sufferers.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Post-Traumatic Headache Concussion, Mild

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

100 patients with PPTH and 100 healthy controls will undergo a deep phenotyping of clinical characteristics and associated comorbidities. This is followed by a single MRI-session for all subjects.

Lastly, the 30 patients with PPTH will participate in a randomized, double-blind, placebo-controlled, 2-way crossover study. These patients will be allocated to receive intravenous infusion of CGRP or placebo (isotonic saline) over 20 minutes on 2 study days.
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Calcitonin Gene-Related Peptide (CGRP)

30 patients with PPTH will be allocated to receive intravenous infusion of 1.5 µg/min calcitonin-gene related peptide over 20 minutes

Other Name: CGRP

Group Type ACTIVE_COMPARATOR

Calcitonin Gene-Related Peptide

Intervention Type DRUG

A randomized clinical trial with a double-blinded, randomized, placebo-controlled crossover design. 30 PPTH patients will be included. All participants will receive continuous intravenous infusion of 1.5 µg/min CGRP over 20 min.

The following variables will be recorded before, during and after infusion (every 10 min over 60 min): headache intensity on a verbal rating scale from 0 to 10 and headache characteristics. At 90 min, participants will be discharged and instructed to fill out a headache diary for 24 hours from start of infusion.

Placebo

30 patients with PPTH wil be allocated to receive 40 mL Placebo (isotonic saline) over 20 minutes.

Other Name: Isotonic Saline

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

A randomized clinical trial with a double-blinded, randomized, placebo-controlled crossover design. 30 PPTH patients will be included. All participants will receive continuous intravenous infusion of 40 mL placebo (isotonic saline) over 20 min.

The following variables will be recorded before, during and after infusion (every 10 min over 60 min): headache intensity on a verbal rating scale from 0 to 10 and headache characteristics. At 90 min, participants will be discharged and instructed to fill out a headache diary for 24 hours from start of infusion.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Calcitonin Gene-Related Peptide

A randomized clinical trial with a double-blinded, randomized, placebo-controlled crossover design. 30 PPTH patients will be included. All participants will receive continuous intravenous infusion of 1.5 µg/min CGRP over 20 min.

The following variables will be recorded before, during and after infusion (every 10 min over 60 min): headache intensity on a verbal rating scale from 0 to 10 and headache characteristics. At 90 min, participants will be discharged and instructed to fill out a headache diary for 24 hours from start of infusion.

Intervention Type DRUG

Placebo

A randomized clinical trial with a double-blinded, randomized, placebo-controlled crossover design. 30 PPTH patients will be included. All participants will receive continuous intravenous infusion of 40 mL placebo (isotonic saline) over 20 min.

The following variables will be recorded before, during and after infusion (every 10 min over 60 min): headache intensity on a verbal rating scale from 0 to 10 and headache characteristics. At 90 min, participants will be discharged and instructed to fill out a headache diary for 24 hours from start of infusion.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

CGRP Isotonic Saline

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 18-65 years of age
* Subject has PPTH in accordance with the diagnostic criteria of the International Headache Society (IHS)
* Concussion (mild traumatic brain injury) occured \> 12 months ago
* Subject, who are fertile women, must be on safe contraceptives

Exclusion Criteria

* Pre-trauma existing primary headache disorder (maximum 1 day/per month with tension-type headache) and medication-overuse headache
* \> 1 episode with a sustained concussion
* Whiplash
* Pregnant or lactating women
* Cardiovascular disease of any kind
* Hypertension on the experimental day
* Hypotension on the experimental day
* Pre-trauma existing psychiatric disorder of any kind - unless well-regulated
* Any anamnestic or clinical signs of any kind deemed relevant for the study by the physician examining the subject
* Any MRI contraindication and a wish of not being informed about unexpected MRI changes
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Danish Headache Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Henrik Schytz

Associate Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Henrik Schytz, MD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Danish Headache Center

Glostrup Municipality, , Denmark

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Denmark

References

Explore related publications, articles, or registry entries linked to this study.

Schytz HW, Smilkov E, Carroll I, Dobrocky T, Al-Khazali HM, Tolnai D, Jensen RH, Amin FM. No evidence of intracranial hypotension in persistent post-traumatic headache: A magnetic resonance imaging study. Cephalalgia. 2025 Apr;45(4):3331024251325556. doi: 10.1177/03331024251325556. Epub 2025 Apr 21.

Reference Type DERIVED
PMID: 40255022 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

H-18011477

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.