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Effect of Levcromakalim in Individuals With Migraine Pretreated With Erenumab (COLLIDE)

Primary Purpose

Migraine Without Aura

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Levcromakalim
Placebo
Sponsored by
Danish Headache Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Migraine Without Aura

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participant has provided informed consent prior to initiation of any study-specific activities/procedures. Age ≥18 years upon entry into screening. History of migraine without aura for ≥12 months with a frequency of 1-5 migraine attacks per month before screening according to the International Headache Society (IHS) Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018), based on medical records and/or patient self-report. Exclusion Criteria: History of any primary headache disorder other than migraine without aura, or tension-type headache with a frequency of ≥5 headache days per month before screening according to the International Headache Society (IHS) Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018), based on medical records and/or patient self-report. History of any secondary headache disorder before screening according to the International Headache Society (IHS) Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018) based on medical records and/or patient self-report. Intake of prophylactic migraine medication within ≤30 days or 5 plasma half-lives (whichever is longer) prior to screening. Prior intake of therapies targeting the CGRP signaling pathway, including anti-CGRP ligand monoclonal antibodies, anti-CGRP receptor monoclonal antibodies, and small molecule CGRP receptor antagonists. The participant is at risk of self-harm or harm to others as evidenced by past suicidal behavior. History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator will pose a risk to participant safety or interfere with the study evaluation, procedures or completion. Female participants of childbearing potential with a positive pregnancy test assessed at screening or day 1 by a urine pregnancy test. Female participants who are pregnant or breastfeeding or plan to become pregnant or breastfeed during participation in the study. Evidence of current pregnancy or breastfeeding per participant self-report or medical records. Participants likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participants' and investigator's knowledge.

Sites / Locations

  • Danish Headache Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Levcromakalim

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Incidence of migraine attack
Difference in incidence of migraine attack (0 to 12 hours) between levcromakalim and placebo. 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).

Secondary Outcome Measures

Incidence of headache
Difference in incidence of headache (0 to 12 hours) between levcromakalim and placebo. 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.
Intensity of headache
Difference in area under the curve (AUC) for headache intensity scores (0 to 12 hours) between levcromakalim and 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.
Diameter of superficial temporal artery
Diameter (mm) of superficial temporal artery is measured as a continuous outcome.

Full Information

First Posted
May 25, 2023
Last Updated
October 22, 2023
Sponsor
Danish Headache Center
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT05889442
Brief Title
Effect of Levcromakalim in Individuals With Migraine Pretreated With Erenumab
Acronym
COLLIDE
Official Title
Effect of Levcromakalim in Individuals With Migraine Pretreated With Erenumab: A Randomized Double-Blind Placebo-Controlled Two-Way Crossover Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
March 9, 2023 (Actual)
Primary Completion Date
June 12, 2023 (Actual)
Study Completion Date
June 12, 2023 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
An outstanding scientific question, that merits further investigation, is whether dilation of intracranial arteries is implicated in the pathogenesis of cephalic pain in migraine. Here, we hypothesize that experimentally-induced dilation of intracranial arteries using intravenous infusion of levcromakalim (a potent vasodilator) induces cephalic pain with migraine-like features in people with migraine, who prior to the infusion are administered erenumab (anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody).

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Levcromakalim
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Levcromakalim
Intervention Description
Continuous intravenous infusion of 20 mL levcromakalim (0.05 mg/min (50 μg/ mL) over 20 minutes
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Continuous intravenous infusion of 20 mL isotonic saline over 20 minutes
Primary Outcome Measure Information:
Title
Incidence of migraine attack
Description
Difference in incidence of migraine attack (0 to 12 hours) between levcromakalim and placebo. 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
12 hours
Secondary Outcome Measure Information:
Title
Incidence of headache
Description
Difference in incidence of headache (0 to 12 hours) between levcromakalim and placebo. 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
12 hours
Title
Intensity of headache
Description
Difference in area under the curve (AUC) for headache intensity scores (0 to 12 hours) between levcromakalim and 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
12 hours
Title
Diameter of superficial temporal artery
Description
Diameter (mm) of superficial temporal artery is measured as a continuous outcome.
Time Frame
1 hour

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participant has provided informed consent prior to initiation of any study-specific activities/procedures. Age ≥18 years upon entry into screening. History of migraine without aura for ≥12 months with a frequency of 1-5 migraine attacks per month before screening according to the International Headache Society (IHS) Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018), based on medical records and/or patient self-report. Exclusion Criteria: History of any primary headache disorder other than migraine without aura, or tension-type headache with a frequency of ≥5 headache days per month before screening according to the International Headache Society (IHS) Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018), based on medical records and/or patient self-report. History of any secondary headache disorder before screening according to the International Headache Society (IHS) Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018) based on medical records and/or patient self-report. Intake of prophylactic migraine medication within ≤30 days or 5 plasma half-lives (whichever is longer) prior to screening. Prior intake of therapies targeting the CGRP signaling pathway, including anti-CGRP ligand monoclonal antibodies, anti-CGRP receptor monoclonal antibodies, and small molecule CGRP receptor antagonists. The participant is at risk of self-harm or harm to others as evidenced by past suicidal behavior. History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator will pose a risk to participant safety or interfere with the study evaluation, procedures or completion. Female participants of childbearing potential with a positive pregnancy test assessed at screening or day 1 by a urine pregnancy test. Female participants who are pregnant or breastfeeding or plan to become pregnant or breastfeed during participation in the study. Evidence of current pregnancy or breastfeeding per participant self-report or medical records. Participants likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participants' and investigator's knowledge.
Facility Information:
Facility Name
Danish Headache Center
City
Copenhagen
ZIP/Postal Code
2600
Country
Denmark

12. IPD Sharing Statement

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Effect of Levcromakalim in Individuals With Migraine Pretreated With Erenumab

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