The Effects of Levcromakalim in Patients With Cluster Headache

NCT05093582 | Completed

• 1 other identifier: H20082689
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cluster Headache

Outcome Measures

Primary Outcomes (1)

• Occurrence of cluster headache attacks

  Experimentally induced cluster headache attacks must fulfill either: 1. Headache described as mimicking the patient's usual cluster headache attack (with or without cephalic autonomic symptom). 2. 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 Outcomes (2)

• Occurrence of headache

  Change from baseline at 90 minutes after drug administration

• Change of headache intensity scores

  Change from baseline at 90 minutes after drug administration

Study Arms (2)

Levcromakalim

ACTIVE COMPARATOR

Intravenous infusion of levcromakalim (1 mg/20 ml). The infusion is administered at constant speed by an automatic pump, lasting 20 minutes.

Drug: Levcromakalim

Placebo

PLACEBO COMPARATOR

Intravenous infusion of placebo (sterile saline, 20 ml). The infusion is administered at constant speed by an automatic pump, lasting 20 minutes.

Drug: Saline

Interventions

Levcromakalim DRUG

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.

Levcromakalim

Saline DRUG

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.

Also known as: Isotonic saline, 0.9% saline

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Primary headache types except above.
• Secondary headache disorders, according to ICHD-3.
• Headache at baseline.
• 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.

Sponsors & Collaborators

• Danish Headache Center: lead

Study Sites (1)

Danish Headache Center

Glostrup Municipality, Copenhagen, 2600, Denmark

Location

Related Publications (1)

• Al-Khazali HM, Deligianni CI, Pellesi L, Al-Karagholi MA, Ashina H, Chaudhry BA, Petersen AS, Jensen RH, Amin FM, Ashina M. Induction of cluster headache after opening of adenosine triphosphate-sensitive potassium channels: a randomized clinical trial. Pain. 2024 Jun 1;165(6):1289-1303. doi: 10.1097/j.pain.0000000000003130. Epub 2023 Dec 19.

  PMID: 38127692 DERIVED

MeSH Terms

Conditions

Cluster Headache

Interventions

Cromakalim; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Messoud Ashina, MD, PhD

  Danish Headache Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 17, 2021
• First Posted: October 26, 2021
• Study Start: June 4, 2021
• Primary Completion: September 27, 2022
• Study Completion: September 27, 2022
• Last Updated: June 28, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)