The Effect of Anti-calcitonin Gene-related Peptide (CGRP) Receptor Antibodies on the Headache Inducing Properties of CGRP and Cilostazol in Migraine Patients

Not Applicable

• Conditions: Migraine Without Aura; Migraine With Aura; Migraine
• Interventions: Drug: Placebo; Drug: Erenumab; Drug: Calcitonin gene-related peptide; Drug: Cilostazol

• Registration Number: NCT04452929
• Lead Sponsor: Danish Headache Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-06-22
• Study First Submitted QC: 2020-06-29
• Study First Posted: 2020-07-01
• Study Start: 2020-07-22
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-06
• Last Update Posted: 2020-10-08
• Primary Completion: 2022-02
• Study Completion: 2022-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 72

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Randomized treatment phase: Placebo	Placebo	Saline placebo single subcutaneous injection at baseline
Randomized treatment phase: Placebo	Calcitonin gene-related peptide	Saline placebo single subcutaneous injection at baseline
Open-label extension treatment phase: Erenumab	Erenumab	Erenumab 140 mg monthly subcutaneous injection for six months after completion of the randomized, double-blinded, placebo-controlled study phase during the open-label extension
Randomized treatment phase: Placebo	Cilostazol	Saline placebo single subcutaneous injection at baseline
Randomized treatment phase: Erenumab	Erenumab	Erenumab 140 mg single subcutaneous injection at baseline
Randomized treatment phase: Erenumab	Cilostazol	Erenumab 140 mg single subcutaneous injection at baseline
Randomized treatment phase: Erenumab	Calcitonin gene-related peptide	Erenumab 140 mg single subcutaneous injection at baseline

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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 (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.
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.
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.

Trial Locations

Locations (1)

Danish Headache Center; 🇩🇰 Glostrup, Denmark