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Effect of Riocigaut on Migraine Attack Induction and Cerebral Vasodilation in Migraine Patients.

Primary Purpose

Migraine Without Aura

Status
Not yet recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Riociguat (BAY 63-2521)
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 focused on measuring Riociguat, Migraine, Cerebral vasodilation, Migraine Without Aura, Headache, Pain, Enzyme Activators, Neurologic Manifestations, Molecular Mechanisms of Pharmacological Action

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: A history of migraine without aura for ≥ 12 months according to the classification criteria of the International Classification of Headache Disorders 3rd Edition (ICHD-3) criteria. Ability to provide written informed consent and receive participant privacy and rights information prior to initiation of any study-specific activities. Male or female participants aged 18-45 years at screening. No migraine preventive treatment at screening or during study conduction. Non-smokers Exclusion Criteria: Any current or previous history of other primary or secondary headache disorder(s) apart from tension type headache ≤ 5 days per month. Lack of ability to differentiate migraine from other headaches Headache within 24 hours before any study related procedures (Provocation Day 1 and Provocation Day 2) - Subjects are however allowed to be re-booked for provocation days according to allowed timelines. Any daily medication apart from contraceptives. Use of any antihypertensive, nitrates or nitric oxide donors or phosphodiesterase inhibitors, CYP3A4 and P-glycoprotein inhibitors, HIV-proteaseinhibitors, ciclosporin A or CYP1A1-inhibitors, antacida and acid-neutreulizing agents (such as aluminium-/magnesiumhydroxid), CYP3A4-inductors (such as bosentan, phenytoin, carbamazepin, phenobarbital and herbal remedies with perikon). Intake of any pro necessitate medication later than 4 times plasma half-life for the specific drug before study start. Women of child-bearing potential not currently using safe contraceptives. Women of child-bearing potential does not include hysterectomized women and women who have been in menopause for at least 2 years. Safe contraceptives include either IUD, birth control pills, surgical sterilization of the woman, depositary gestagen, barrier prevention or sexual abstinence. Pregnant or breastfeeding women Positive pregnancy urine screening on screening day or provocation days. A medical history or clinical signs of Hypertension (systolic blood pressure >150mmHg and/or diastolic blood pressure >100mmHg) Hypotension (systolic blood pressure <100mmHg and/or diastolic blood pressure <50mmHg) Electrocardiogram (ECG) with any clinically significant abnormalities at screening determined by the investigator, including but not limited to, prolonged PQ or QTc interval, signs of arrythmias, ischemia or left/right ventricle dysfunction/hypertrophy. A medical history or clinical signs of pulmo-/cardiovascular disease including cerebrovascular disease. A family history of severe cardiac disease. A medical history or clinical signs of clinically significant psychiatric illness per investigator opinion. The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior. A medical history or clinical signs of substance or alcohol abuse A medical 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 site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion. Any history of hypersensitivity to riociguat. Subjects who do not want information about crucial pathological findings during the study Subject likely to not be available to complete all protocol-required study visits or procedures, and/or comply with all required study procedures to the best of the subject and study investigator's knowledge.

Sites / Locations

  • Danish Headache Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Riociguat / Placebo

Placebo / Riociguat

Arm Description

Riociguat or Placebo as oral capsule in randomized order

Riociguat or Placebo as oral capsule in randomized order

Outcomes

Primary Outcome Measures

Difference in incidence of migraine attacks between riociguat and placebo during a 12-hour observational period after ingestion.
Data will be collected with a questionnaire.

Secondary Outcome Measures

Difference in superficial temporal artery (STA) diameter between baseline and 90 minutes after receiving riociguat compared to placebo.
Measured by high resolution ultrasonography.
Difference in superficial temporal artery (STA) diameter between baseline and onset of migraine attack after receiving riociguat (maximum 6 hours after receiving riociguat) compared to placebo.
STA diameter will be measured by high resolution ultrasonography. Data on migraine attack will be collected with a questionnaire.
Difference in middle cerebral artery (MCA) blood flow velocity between baseline and 90 minutes after receiving riociguat compared to placebo.
Measured by transcranial doppler.
Difference in middle cerebral artery (MCA) blood flow velocity between baseline and onset of migraine attack after receiving riociguat (maximum 6 hours after receiving riociguat) compared to placebo.
MCA blood flow velocity will be measured by transcranial doppler. Data on migraine attack will be collected with a questionnaire.
Difference in incidence of headache (>0 on Numeric Rating Scale (NRS) from 0 to 10, where 0="no pain" versus 1-10="pain") between riociguat and placebo during a 12-hour observational period after ingestion.
Data will be collected with a questionnaire.
Difference in severity of headache rated on 11-point NRS from 0 ("no pain") to 10 ("worst pain imaginable") between riociguat and placebo during a 12-hour observational period after ingestion.
Data will be collected with a questionnaire.

Full Information

First Posted
February 20, 2023
Last Updated
February 20, 2023
Sponsor
Danish Headache Center
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1. Study Identification

Unique Protocol Identification Number
NCT05750446
Brief Title
Effect of Riocigaut on Migraine Attack Induction and Cerebral Vasodilation in Migraine Patients.
Official Title
Riociguat (BAY 63-2521), a Stimulator of Soluble Guanylate Cyclase (sGC) - Migraine Induction and Cerebral Vasodilation in Migraine Patients.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2023 (Anticipated)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
May 31, 2024 (Anticipated)

3. Sponsor/Collaborators

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

4. Oversight

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

5. Study Description

Brief Summary
This double-blind, randomized, placebo-controlled cross-over clinical trial aims to investigate the effects of riocigaut on migraine inducing properties and cerebral arteries in patients with migraine.
Detailed Description
The investigators believe that activation of sGC could play a role in migraine pathophysiology and propose that stimulation with riociguat causes migraine attacks alongside cranial arterial dilation in patients with migraine. Twenty-one patients with migraine will participate at a screening visit and, if eligible, on two separate study days, where participants, in a randomized cross-over fashion, will ingest either riociguat (active comparator arm) or placebo (placebo comparator arm), serving as their own controls. On the two separate study days the investigators will measure change in diameter of superficial temporal artery and middle cerebral artery blood flow velocity, heart rate, blood pressure and register possible headache/migraine including associated symptoms until 6 hours after intake of riociguat or placebo. At home participants are expected to fill out a headache diary until 12 hours from intake of riociguat or placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine Without Aura
Keywords
Riociguat, Migraine, Cerebral vasodilation, Migraine Without Aura, Headache, Pain, Enzyme Activators, Neurologic Manifestations, Molecular Mechanisms of Pharmacological Action

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Riociguat / Placebo
Arm Type
Other
Arm Description
Riociguat or Placebo as oral capsule in randomized order
Arm Title
Placebo / Riociguat
Arm Type
Other
Arm Description
Riociguat or Placebo as oral capsule in randomized order
Intervention Type
Drug
Intervention Name(s)
Riociguat (BAY 63-2521)
Other Intervention Name(s)
Adempas
Intervention Description
A selective stimulator of soluble guanylate cyclase (sGC)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Difference in incidence of migraine attacks between riociguat and placebo during a 12-hour observational period after ingestion.
Description
Data will be collected with a questionnaire.
Time Frame
0-12 hours
Secondary Outcome Measure Information:
Title
Difference in superficial temporal artery (STA) diameter between baseline and 90 minutes after receiving riociguat compared to placebo.
Description
Measured by high resolution ultrasonography.
Time Frame
0-90 minutes
Title
Difference in superficial temporal artery (STA) diameter between baseline and onset of migraine attack after receiving riociguat (maximum 6 hours after receiving riociguat) compared to placebo.
Description
STA diameter will be measured by high resolution ultrasonography. Data on migraine attack will be collected with a questionnaire.
Time Frame
0-6 hours (max)
Title
Difference in middle cerebral artery (MCA) blood flow velocity between baseline and 90 minutes after receiving riociguat compared to placebo.
Description
Measured by transcranial doppler.
Time Frame
0-90 minutes
Title
Difference in middle cerebral artery (MCA) blood flow velocity between baseline and onset of migraine attack after receiving riociguat (maximum 6 hours after receiving riociguat) compared to placebo.
Description
MCA blood flow velocity will be measured by transcranial doppler. Data on migraine attack will be collected with a questionnaire.
Time Frame
0-6 hours (max)
Title
Difference in incidence of headache (>0 on Numeric Rating Scale (NRS) from 0 to 10, where 0="no pain" versus 1-10="pain") between riociguat and placebo during a 12-hour observational period after ingestion.
Description
Data will be collected with a questionnaire.
Time Frame
0-12 hours
Title
Difference in severity of headache rated on 11-point NRS from 0 ("no pain") to 10 ("worst pain imaginable") between riociguat and placebo during a 12-hour observational period after ingestion.
Description
Data will be collected with a questionnaire.
Time Frame
0-12 hours
Other Pre-specified Outcome Measures:
Title
Difference in use of rescue medication to treat headache and migraine attack between riociguat and placebo during a 12-hour observational period after ingestion.
Description
Exploratory outcome. Data will be collected with a questionnaire.
Time Frame
0-12 hours
Title
Difference in superficial temporal artery (STA) diameter in the time-course from baseline until 6 hours after receiving riociguat compared to placebo.
Description
Exploratory outcome. Measured by high resolution ultrasonography.
Time Frame
0-6 hours
Title
Difference in middle cerebral artery (MCA) blood flow velocity in the time-course from baseline until 6 hours after receiving riociguat compared to placebo.
Description
Exploratory outcome. Measured by transcranial doppler.
Time Frame
0-6 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A history of migraine without aura for ≥ 12 months according to the classification criteria of the International Classification of Headache Disorders 3rd Edition (ICHD-3) criteria. Ability to provide written informed consent and receive participant privacy and rights information prior to initiation of any study-specific activities. Male or female participants aged 18-45 years at screening. No migraine preventive treatment at screening or during study conduction. Non-smokers Exclusion Criteria: Any current or previous history of other primary or secondary headache disorder(s) apart from tension type headache ≤ 5 days per month. Lack of ability to differentiate migraine from other headaches Headache within 24 hours before any study related procedures (Provocation Day 1 and Provocation Day 2) - Subjects are however allowed to be re-booked for provocation days according to allowed timelines. Any daily medication apart from contraceptives. Use of any antihypertensive, nitrates or nitric oxide donors or phosphodiesterase inhibitors, CYP3A4 and P-glycoprotein inhibitors, HIV-proteaseinhibitors, ciclosporin A or CYP1A1-inhibitors, antacida and acid-neutreulizing agents (such as aluminium-/magnesiumhydroxid), CYP3A4-inductors (such as bosentan, phenytoin, carbamazepin, phenobarbital and herbal remedies with perikon). Intake of any pro necessitate medication later than 4 times plasma half-life for the specific drug before study start. Women of child-bearing potential not currently using safe contraceptives. Women of child-bearing potential does not include hysterectomized women and women who have been in menopause for at least 2 years. Safe contraceptives include either IUD, birth control pills, surgical sterilization of the woman, depositary gestagen, barrier prevention or sexual abstinence. Pregnant or breastfeeding women Positive pregnancy urine screening on screening day or provocation days. A medical history or clinical signs of Hypertension (systolic blood pressure >150mmHg and/or diastolic blood pressure >100mmHg) Hypotension (systolic blood pressure <100mmHg and/or diastolic blood pressure <50mmHg) Electrocardiogram (ECG) with any clinically significant abnormalities at screening determined by the investigator, including but not limited to, prolonged PQ or QTc interval, signs of arrythmias, ischemia or left/right ventricle dysfunction/hypertrophy. A medical history or clinical signs of pulmo-/cardiovascular disease including cerebrovascular disease. A family history of severe cardiac disease. A medical history or clinical signs of clinically significant psychiatric illness per investigator opinion. The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior. A medical history or clinical signs of substance or alcohol abuse A medical 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 site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion. Any history of hypersensitivity to riociguat. Subjects who do not want information about crucial pathological findings during the study Subject likely to not be available to complete all protocol-required study visits or procedures, and/or comply with all required study procedures to the best of the subject and study investigator's knowledge.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nadja B Rasmussen, MD
Phone
+4538633557
Email
nadja.bredo.rasmussen@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Messoud Ashina, MD, Ph.D., DMSc.
Phone
+45-38633054
Email
messoud.ashina@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Messoud B Ashina, MD, Ph.D., DMSc.
Organizational Affiliation
Danish Headache Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Danish Headache Center
City
Copenhagen
State/Province
Glostrup
ZIP/Postal Code
2600
Country
Denmark
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nadja B Rasmussen
Phone
+4538633557
Email
nadja.bredo.rasmussen@regionh.dk

12. IPD Sharing Statement

Plan to Share IPD
No

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Effect of Riocigaut on Migraine Attack Induction and Cerebral Vasodilation in Migraine Patients.

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