This study aims to explore the effect of Ivabradine on Levcromakalim-induced migraine in individuals with migraine without aura.
Hyperpolarization-activated cation (HCN) channels have recently been implicated in neuropathic and inflammatory pain processes through their hyperfunction and/or overexpression. HCN channels may play a significant role in migraine pathophysiology, as 1) both an inflammatory and a neuropathic component has been hypothesized to contribute to migraine, and 2) HCN channel activity is facilitated by cyclic nucleotides, e.g. cAMP and cGMP (molecules thought to be central in migraine pathophysiology) and increases in extracellular K+ concentration. Opening of adenosine 5'-triphosphate-sensitive potassium channels (KATP channels) using Levcromakalim causes migraine attacks with and without aura in a high proportion of patients. KATP channel activation leads to hyperpolarization, which in turn could increase the open probability of HCN channels. This study aims to explore the effects of Ivabradine on Levcromakalim-induced migraine in individuals with migraine without aura. The investigators anticipate that this project will contribute greatly to the current understanding of migraine pathophysiology and the hypothesized role of HCN channels in migraine pain mechanisms. This is of great interest in future research, as such knowledge is an important prerequisite for further investigation and understanding of intracellular signalling mechanisms in migraine, which in turn will lead to the development of more effective and mechanism-based drugs.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
37
20 min infusion of 1 mg Levcromakalim followed by either oral Ivabradine or Placebo.
15 mg oral Ivabradine.
Oral placebo (calcium supplements).
Danish Headache Centre, Rigshospitalet-Glostrup
Glostrup, Region Sjælland, Denmark
Danish Headache Center
Glostrup Municipality, Denmark
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).
Time frame: Assessed from baseline to 12 hours after infusion of levcromakalim
Incidence of headache
Incidence of headache is defined as headache intensity ≥1 as measured by a numerical rating scale (NRS) from 0 to 10. It is a verbally declared scale from 0 to 10, where 0 is no pain; 10 is the worst pain imaginable
Time frame: Assessed from baseline to 12 hours after infusion of levcromakalim
Intensity of headache
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 pain; 10 is the worst pain imaginable.
Time frame: 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)
Changes in cerebral hemodynamics will be assessed using Transcranial Doppler Ultrasound (TCD) (2 Mhz, DWL) to measure the velocity of middle cerebral artery (VMCA) blood flow bilaterally, and high-frequency ultrasound (Dermascan C, Cortex Technology, Denmark) to measure the diameter of the superficial temporal artery (STA) bilaterally.
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Time frame: Assessed from baseline until 150 minutes after levcromakalim infusion.
Changes in blood pressure
Changes in blood pressure (systolic and diastolic) over time.
Time frame: Assessed from baseline until 150 minutes after levcromakalim infusion.
Heart rate
Changes in heart rate over time.
Time frame: Assessed from baseline until 150 minutes after levcromakalim infusion.
Incidence of adverse events
Participants are instructed to inform the investigators in the case of adverse events.
Time frame: Assessed from baseline to 12 hours after infusion of Levcromakalim.