Effect of Ivabradine on Levcromakalim-Induced Symptoms in Individuals With Migraine Without Aura (ILIM)

NCT04853797 | Completed

• 1 other identifier: Ivabradine H-20061329
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to explore the effect of Ivabradine on Levcromakalim-induced migraine in individuals with migraine without aura.

Conditions

Headache; Migraine Without Aura

Outcome Measures

Primary Outcomes (1)

• Incidence of migraine attacks

  A migraine attack is defined as an attack fulfilling either (i) or (ii): (i) Headache fulfilling criteria C and D for migraine without aura according to the International Headache Society criteria: C. Headache has at least two of the following characteristics: * unilateral location * pulsating quality * moderate or severe pain intensity (moderate to severe pain intensity is considered ≥4 on verbal rating scale) * aggravation by cough (in-hospital phase) or causing avoidance of routine physical activity (out-hospital phase) D. During headache at least one of the following: * nausea and/or vomiting * photophobia and phonophobia (ii) Headache described as mimicking the patient's usual migraine attack and treated with acute migraine medication (rescue medication).

  Assessed from baseline to 12 hours after infusion of levcromakalim

Secondary Outcomes (6)

• Incidence of headache

  Assessed from baseline to 12 hours after infusion of levcromakalim

• Intensity of headache

  Assessed from baseline to 12 hours after infusion of levcromakalim

• Changes in cerebral hemodynamics (velocity of blood flow in middle cerebral artery and diameter of superficial temporal artery) assessed using Transcranial Doppler Ultrasound (TCD) and high-frequency ultrasound (Dermascan C, Cortex Technology, Denmark)

  Assessed from baseline until 150 minutes after levcromakalim infusion.

• Changes in blood pressure

  Assessed from baseline until 150 minutes after levcromakalim infusion.

• Heart rate

  Assessed from baseline until 150 minutes after levcromakalim infusion.

Study Arms (2)

Levcromakalim - Ivabradine

ACTIVE COMPARATOR

Infusion of levcromakalim (2.5 nmol minutes-1 over 20 minutes) followed by oral administration of ivabradine (15 mg orally).

Drug: Levcromakalim; Drug: Ivabradine

Levcromakalim - Placebo

PLACEBO COMPARATOR

Infusion of levcromakalim (2.5 nmol minutes-1 over 20 minutes) followed by oral administration of placebo.

Drug: Levcromakalim; Drug: Placebo

Interventions

Levcromakalim DRUG

20 min infusion of 1 mg Levcromakalim followed by either oral Ivabradine or Placebo.

Levcromakalim - Ivabradine; Levcromakalim - Placebo

Ivabradine DRUG

15 mg oral Ivabradine.

Levcromakalim - Ivabradine

Placebo DRUG

Oral placebo (calcium supplements).

Levcromakalim - Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Be able to give voluntary written informed consent to participate.
• Have a diagnosis of episodic migraine without aura according to The International Classification of Headache Disorders 3rd Edition.
• Be in good general health and without any cardio- or cerebrovascular diseases, psychiatric disorders or other severe comorbidities.
• Be 18-60 years of age.
• Have a weight between 50-100 kg.
• Be without any chronic use of medicine.
• Have a negative urine-human chorionic gonadotropin (hCG) test at the screening visit if they are female of childbearing potential.

You may not qualify if:

• Suffer from tension type headache, as defined by the The International Classification of Headache Disorders 3rd Edition, more than five days a month on average in the last year.
• Are diagnosed with any primary headache disorder apart from migraine without aura as de-fined in The International Classification of Headache Disorders 3rd Edition (relating to tension type headache, see above).
• Suffer from any headache 48 hours prior to the start of the experiment or any migraine 72 hours prior to the start of the experiment.
• Are allergic to ivabradine or levcromakalim.
• Are lactose intolerant (due to Ivabradine tablets containing lactose).
• Have a daily intake of any medicine other than oral contraception or use of drugs or other ed-ibles/beverages with potential serious interactions with ivabradine
• Have a history of personal/familial or clinical signs of: cardiovascular and cerebrovascular disease (Long QT Syndrome, Cardiac dysrhythmia, Bradycardia, i.e. a resting heart rate of \< 60 bpm at screening, Amnestic information or clinical signs of hyper- or hypotension (Hypertension (systolic blood pressure \> 150 mmHg and / or diastolic blood pressure \> 100 mmHg)/Hypotension (systolic blood pressure \< 90 mm Hg and / or diastolic blood pressure \< 50 mmHg)), Heart failure (NYHA II or higher)); Psychiatric conditions; Drug abuse of any kind; Smoking; Other comorbidities or clinical signs of diseases of any kind considered by the investigating physician to make the participant ineligible because of safety concerns).
• Are pregnant, breastfeeding or not using appropriate contraception.
• Do not want any information on significant pathological findings in the study.

Sponsors & Collaborators

• Danish Headache Center: lead

Study Sites (2)

Danish Headache Centre, Rigshospitalet-Glostrup

Glostrup, Region Sjælland, 2600, Denmark

Location

Danish Headache Center

Glostrup Municipality, 2600, Denmark

Location

MeSH Terms

Conditions

Headache; Migraine without Aura

Interventions

Cromakalim; Ivabradine

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Migraine Disorders; 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; Benzazepines

Study Officials

• Messoud Ashina, Prof.

  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: Principal investigator

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: April 21, 2021
• Study Start: May 11, 2021
• Primary Completion: July 6, 2025
• Study Completion: July 6, 2025
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)