Migraine, Migraine With Aura, Migraine Without Aura
Conditions
Brief summary
A randomized, double-blind, placebo-controlled, parallel study to investigate the effect of erenumab in calcitonin-gene related peptide and cilostazol experimental models of migraine in humans. Followed by a 6-month open-label extension.
Interventions
DRUGErenumab
Subcutaneous injection of 140 mg erenumab.
DRUGPlacebo
Subcutaneous injection of saline placebo.
Intravenous infusion of 1.5ug/min calcitonin gene-related peptide over 20 minutes.
DRUGCilostazol
Oral intake of 200 mg cilostazol.
Sponsors
Novartis Pharmaceuticals
Danish Headache Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomized, double-blinded, placebo-controlled, parallel study followed by a 6-month open-label extension.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patients with migraine with or without aura according to the International Classification of Headache Disorders with a frequency of ≥4 migraine days per month * 50-100 kg weight * Participants of childbearing potential must use safe contraception (birth control) or be sexually abstinent
Exclusion criteria
* Any other primary headache disorder according to the International Classification of Headache Disorders except for tension-type headache * Any secondary headache disorder according to the International Classification of Headache Disorders * Migraine attack during the preceding 48 hours on provocation day * Headache during the preceding 24 hours on provocation day * Treatment with monoclonal antibodies or participation in clinical trials with monoclonal antibodies during the preceding year * Daily consumption of any other drug/medication than oral contraception (birth control) * Consumption of any other drug/medication later than four times the plasma half-time of the drug on provocation day except for oral contraception * Pregnant or active breastfeeding participants * Any cardiovascular diseases including cerebrovascular disorders * Information in patient history or during physical examination indicating psychiatric disorders or substance abuse * Information in patient history or during physical examination that the screening physician deems relevant for participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Migraine-like attack | Before (-5 min) and after administration of (+12 hours) of experimental trigger | The incidence of migraine-like attack after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo. A migraine-like attack is defined 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; and (ii) Headache described as mimicking the patient's usual migraine attack and treated with acute migraine medication (rescue medication). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemodynamics (superficial temporal artery) | Before (-5 min) and after administration of (+90 minutes) of experimental trigger | Change in diameter (mm) of superficial temporal artery after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo. |
| Hemodynamics (radial artery) | Before (-5 min) and after administration of (+90 minutes) of experimental trigger | Change in diameter (mm) of radial artery after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo. |
| Neuropeptide plasma concentrations (CGRP) | (1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase | 1. Change in plasma concentrations of calcitonin gene-related peptide (CGRP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo. 2. Change in plasma concentrations of calcitonin gene-related peptide during the open-label treatment phase. |
| Neuropeptide plasma concentrations (VIP) | (1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase | 1. Change in plasma concentrations of vasoactive intestinal peptide (VIP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo. 2. Change in plasma concentrations of vasoactive intestinal peptide (VIP) during the open-label treatment phase. |
| Neuropeptide plasma concentrations (PACAP) | (1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase | 1. Change in plasma concentrations of pituitary adenylate cyclase-activating peptide (PACAP) after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo. 2. Change in plasma concentrations of pituitary adenylate cyclase-activating peptide (PACAP) during the open-label treatment phase. |
| Headache intensity | Before (-5 min) and after administration of (+12 hours) of experimental trigger | Change in headache intensity after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo. 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. |
| Facial temperature | Before (-5 min) and after administration of (+90 minutes) of experimental trigger | Change in facial temperature after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo. |
| Headache day | Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase | Change in number of headache days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase. |
| Migraine day | Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase | Change in number of migraine days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase. |
| ≥50% responder rate | Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase | Proportion of participants with a ≥50% reduction in number of migraine days per month after administration of erenumab from baseline compared to the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase. |
| Facial flushing | Before (-5 min) and after administration of (+90 minutes) of experimental trigger | Change in facial skin flushing after administration of calcitonin-gene related peptide or cilostazol in patients with migraine pretreated with erenumab compared to patients with migraine pretreated with placebo. |
Countries
Denmark
Contacts
Primary ContactThien P Do, MD
Outcome results
None listed