The Effects of Levcromakalim in Patients With Cluster Headache

The Headache-inducing Effects of Levcromakalim in Patients With Cluster Headache

Cluster headache is a primary headache disorder characterized by attacks of unilateral headache of short duration and severe pain intensity. There is an unmet need to understand the underlying disease mechanisms that will ultimately lead to the development of disease-specific medicines. Until now, it has been suggested that the calcitonin gene-related peptide (CGRP) plays a major role in the initiation of a cluster headache attack, possibly involving the ATP-sensitive potassium channels. The current study aims to determine whether the opening of ATP-sensitive potassium channels triggers cluster headache attacks in patients with cluster headache.

Study Overview

• Status: Completed
• Conditions: Cluster Headache
• Intervention / Treatment: Drug: Levcromakalim; Drug: Saline

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Glostrup, Copenhagen, Denmark, 2600
      • Danish Headache Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Cluster headache patients meeting ICHD-3 criteria for episodic and chronic cluster headache of either sex. Patients were defined as having episodic cluster headache in the active phase when they had usual attacks within the last 30 days, episodic cluster headache in the remission phase when they were attack-free for at least 30 days, or chronic cluster headache when they had not had more than 30 consecutively attack-free days over the last 12 months or longer.
• Weight between 50 and 100 kg.
• All preventive medications, except steroid treatments or greater occipital nerve blockade within 30 days, were allowed with stable dosing.
• Negative urinary HCG at baseline.

Exclusion Criteria:

• Primary headache types except above.
• Secondary headache disorders, according to ICHD-3.
• Headache at baseline.
• Anamnestic information or clinical signs of (at inclusion date) hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg) or hypotension (systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 50 mmHg)
• Known severe or treatment-requiring cardiovascular disease including cerebrovascular disease.
• Anamnestic or clinical evidence of mental disorder or substance abuse.
• Anamnestic or clinical evidence of any disease considered by the investigating physician to be relevant to participation in the study.
• Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Levcromakalim; Intravenous infusion of levcromakalim (1 mg/20 ml). The infusion is administered at constant speed by an automatic pump, lasting 20 minutes.	Drug: Levcromakalim; 12 active episodic patients, 15 episodic patients in remission and 20 chronic patients of both genders are randomized to receive a 20-minute infusion of levcromakalim and/or sterile saline on two days, with at least 3 days in between.
Placebo Comparator: Placebo; Intravenous infusion of placebo (sterile saline, 20 ml). The infusion is administered at constant speed by an automatic pump, lasting 20 minutes.	Drug: Saline; 12 active episodic patients, 15 episodic patients in remission and 20 chronic patients of both genders are randomized to receive a 20-minute infusion of levcromakalim and/or sterile saline on two days, with at least 3 days in between.; Other Names: 0.9% saline; Isotonic saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of cluster headache attacks	Experimentally induced cluster headache attacks must fulfill either: Headache described as mimicking the patient's usual cluster headache attack (with or without cephalic autonomic symptom).; Headache fulfilling criteria A and B for cluster headache according to International Classification of Headache Disorders criteria: A. Severe unilateral pain lasting 15 to 180 minutes. B. Either or both of the following: At least 1 cephalic autonomic symptom ipsilateral to the headache.; A sense of restlessness or agitation.	Change from baseline at 90 minutes after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of headache	Yes/no questions.	Change from baseline at 90 minutes after drug administration
Change of headache intensity scores	Headache intensity scores are measured by a numerical rating scale (NRS). It is a verbally declared scale from 0 to 10, where 0 is no headache; 1 is a very mild headache, including a feeling of pressing or throbbing; 5 is a moderate headache; 10 is the worst imaginable headache.	Change from baseline at 90 minutes after drug administration

Collaborators and Investigators

• Sponsor: Danish Headache Center
• Investigators: Principal Investigator: Messoud Ashina, MD, PhD, Danish Headache Center

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2021
• Primary Completion (Actual): September 27, 2022
• Study Completion (Actual): September 27, 2022

Study Registration Dates

• First Submitted: September 17, 2021
• First Submitted That Met QC Criteria: October 25, 2021
• First Posted (Actual): October 26, 2021

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Trigeminal Autonomic Cephalalgias; Headache; Cluster Headache; Physiological Effects of Drugs; Antihypertensive Agents; Vasodilator Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Cromakalim
• Other Study ID Numbers: H20082689

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No