The Effects of Levcromakalim in Patients With Cluster Headache

Study Overview
=================
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.

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

Conditions
-----------------
Cluster Headache

Intervention / Treatment
-----------------
* Drug: Levcromakalim
* Drug: Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levcromakalim<br>Intravenous infusion of levcromakalim (1 mg/20 ml). The infusion is administered at constant speed by an automatic pump, lasting 20 minutes. | Drug: Levcromakalim<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Intravenous infusion of placebo (sterile saline, 20 ml). The infusion is administered at constant speed by an automatic pump, lasting 20 minutes. | Drug: Saline<br>* 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.<br>* Other names: 0.9% 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 |