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

Migraine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04452929
• Other study ID #: CGRP2020
• Status: Recruiting
• Phase: N/A
• Start date: July 22, 2020
• Est. completion date: July 2022

Study information

• Verified date: October 2020
• Source: Danish Headache Center
• Contact: Thien P Do, MD
• Phone: 004541414117
• Email: tdoo0001[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: July 2022
• Est. primary completion date: February 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Headache
• Migraine
• Migraine Disorders
• Migraine with Aura
• Migraine Without Aura

Intervention

Drug:
• Erenumab
Subcutaneous injection of 140 mg erenumab.
• Placebo
Subcutaneous injection of saline placebo.
• Calcitonin gene-related peptide
Intravenous infusion of 1.5ug/min calcitonin gene-related peptide over 20 minutes.
• Cilostazol
Oral intake of 200 mg cilostazol.

Locations

Country	Name	City	State
Denmark	Danish Headache Center	Glostrup

Sponsors (2)

Lead Sponsor	Collaborator
Danish Headache Center	Novartis Pharmaceuticals

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Migraine-like attack	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).	Before (-5 min) and after administration of (+12 hours) of experimental trigger
Secondary	Headache intensity	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.	Before (-5 min) and after administration of (+12 hours) of experimental trigger
Secondary	Hemodynamics (superficial temporal artery)	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.	Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Secondary	Hemodynamics (radial artery)	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.	Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Secondary	Neuropeptide plasma concentrations (CGRP)	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.; Change in plasma concentrations of calcitonin gene-related peptide during the open-label treatment phase.	(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
Secondary	Neuropeptide plasma concentrations (VIP)	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.; Change in plasma concentrations of vasoactive intestinal peptide (VIP) during the open-label treatment phase.	(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
Secondary	Neuropeptide plasma concentrations (PACAP)	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.; Change in plasma concentrations of pituitary adenylate cyclase-activating peptide (PACAP) during the open-label treatment phase.	(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
Secondary	Facial flushing	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.	Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Secondary	Facial temperature	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.	Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Secondary	Headache day	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.	Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase
Secondary	Migraine day	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.	Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase
Secondary	=50% responder rate	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.	Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase