Hypersensitivity to Opening of ATP-Sensitive Potassium Channels in Post-Traumatic Headache

Sponsor

Danish Headache Center (Other)

Overall Status

Completed

CT.gov ID

NCT05243953

Collaborator

(none)

Enrollment

Location

Arms

3.5

Actual Duration (Months)

5.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim is to investigate whether opening of ATP-sensitive potassium (KATP) channels induces headache with migraine-like features in people with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI).

Condition or Disease	Intervention/Treatment	Phase
Post-Traumatic Headache	Drug: Levcromakalim Drug: Placebo	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Hypersensitivity to Opening of ATP-Sensitive Potassium Channels in Post-Traumatic Headache: A Randomized Clinical Trial

Actual Study Start Date :

Mar 21, 2022

Actual Primary Completion Date :

Jul 7, 2022

Actual Study Completion Date :

Jul 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Levcromakalim A time- and volume-controlled infusion pump is used to administer levcromakalim by intravenous infusion over 20 minutes.	Drug: Levcromakalim Study participants will be allocated to receive continuous intravenous infusion of 0.05 mg/min (20 ml of 50 mg/ml) levcromakalim.
Placebo Comparator: Placebo (isotonic saline) A time- and volume-controlled infusion pump is used to administer placebo (isotonic saline) by intravenous infusion over 20 minutes.	Drug: Placebo Study participants will be allocated to receive continuous intravenous infusion of 20 mL placebo (isotonic saline). Other Names: Isotonic Saline

Arm

Intervention/Treatment

Experimental: Levcromakalim

A time- and volume-controlled infusion pump is used to administer levcromakalim by intravenous infusion over 20 minutes.

Drug: Levcromakalim

Study participants will be allocated to receive continuous intravenous infusion of 0.05 mg/min (20 ml of 50 mg/ml) levcromakalim.

Placebo Comparator: Placebo (isotonic saline)

A time- and volume-controlled infusion pump is used to administer placebo (isotonic saline) by intravenous infusion over 20 minutes.

Drug: Placebo

Study participants will be allocated to receive continuous intravenous infusion of 20 mL placebo (isotonic saline).

Other Names:

Isotonic Saline

Outcome Measures

Primary Outcome Measures

Incidence of Migraine-Like Headache [12 Hours]
Difference in incidence of headache with migraine-like features (0 to 12 hours) between levcromakalim and placebo.

Secondary Outcome Measures

Headache Intensity Scores [12 Hours]
Difference in area under the curve (AUC) for headache intensity scores (0 to 12 hours) between levcromakalim and placebo.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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