search
Back to results

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

Primary Purpose

Migraine, Migraine Without Aura, Migraine With Aura

Status
Unknown status
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Erenumab
Placebo
Calcitonin gene-related peptide
Cilostazol
Sponsored by
Danish Headache Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for Migraine

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Danish Headache CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Other

Arm Label

Randomized treatment phase: Erenumab

Randomized treatment phase: Placebo

Open-label extension treatment phase: Erenumab

Arm Description

Erenumab 140 mg single subcutaneous injection at baseline

Saline placebo single subcutaneous injection at baseline

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
≥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.

Full Information

First Posted
June 22, 2020
Last Updated
October 6, 2020
Sponsor
Danish Headache Center
Collaborators
Novartis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT04452929
Brief Title
The Effect of Anti-calcitonin Gene-related Peptide (CGRP) Receptor Antibodies on the Headache Inducing Properties of CGRP and Cilostazol in Migraine Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
July 22, 2020 (Actual)
Primary Completion Date
February 2022 (Anticipated)
Study Completion Date
July 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Danish Headache Center
Collaborators
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine, Migraine Without Aura, Migraine With Aura

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blinded, placebo-controlled, parallel study followed by a 6-month open-label extension.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Randomized treatment phase: Erenumab
Arm Type
Active Comparator
Arm Description
Erenumab 140 mg single subcutaneous injection at baseline
Arm Title
Randomized treatment phase: Placebo
Arm Type
Placebo Comparator
Arm Description
Saline placebo single subcutaneous injection at baseline
Arm Title
Open-label extension treatment phase: Erenumab
Arm Type
Other
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Erenumab
Other Intervention Name(s)
Aimovig®
Intervention Description
Subcutaneous injection of 140 mg erenumab.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline placebo
Intervention Description
Subcutaneous injection of saline placebo.
Intervention Type
Drug
Intervention Name(s)
Calcitonin gene-related peptide
Intervention Description
Intravenous infusion of 1.5ug/min calcitonin gene-related peptide over 20 minutes.
Intervention Type
Drug
Intervention Name(s)
Cilostazol
Intervention Description
Oral intake of 200 mg cilostazol.
Primary Outcome Measure Information:
Title
Migraine-like attack
Description
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).
Time Frame
Before (-5 min) and after administration of (+12 hours) of experimental trigger
Secondary Outcome Measure Information:
Title
Headache intensity
Description
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.
Time Frame
Before (-5 min) and after administration of (+12 hours) of experimental trigger
Title
Hemodynamics (superficial temporal artery)
Description
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.
Time Frame
Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Title
Hemodynamics (radial artery)
Description
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.
Time Frame
Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Title
Neuropeptide plasma concentrations (CGRP)
Description
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.
Time Frame
(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
Title
Neuropeptide plasma concentrations (VIP)
Description
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.
Time Frame
(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
Title
Neuropeptide plasma concentrations (PACAP)
Description
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.
Time Frame
(1) Before (-5 min) and after administration of (+60 minutes) of experimental trigger; (2) 24-week open-label treatment phase
Title
Facial flushing
Description
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.
Time Frame
Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Title
Facial temperature
Description
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.
Time Frame
Before (-5 min) and after administration of (+90 minutes) of experimental trigger
Title
Headache day
Description
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.
Time Frame
Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase
Title
Migraine day
Description
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.
Time Frame
Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase
Title
≥50% responder rate
Description
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.
Time Frame
Baseline and the last 3 months (months 4, 5, and 6) of the 24-week open-label treatment phase

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thien P Do, MD
Phone
004541414117
Email
tdoo0001@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thien P Do, MD
Organizational Affiliation
Danish Headache Center
Official's Role
Study Director
Facility Information:
Facility Name
Danish Headache Center
City
Glostrup
ZIP/Postal Code
2600
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thien P Do, MD
Phone
004541414117
Email
tdoo0001@regionh.dk
First Name & Middle Initial & Last Name & Degree
Messoud Ashina, MD, PhD, DMSc
First Name & Middle Initial & Last Name & Degree
Thien P Do, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs