Effect of Riocigaut on Cerebral Vasodilation and Headache Induction in Healthy Volunteers

NCT ID: NCT05582811

Last Updated: 2024-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-26
• Study Completion Date: 2023-06-01

Brief Summary

This double-blind, randomized, placebo-controlled cross-over clinical trial aims to investigate the effects of riocigaut on cerebral arteries and headache inducing properties in healthy volunteers.

Detailed Description

The investigators believe that activation of sGC could play a role in migraine pathophysiology and propose that stimulation with riociguat causes cranial arterial dilation alongside headache in healthy volunteers.

Twelve healthy volunteers 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 and register possible headache until 4 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.

Leading up to the main study described above, the investigators will conduct a pilot dose-finding study (experimental arm) of increasing doses of riociguat, 2,5mg and 5mg respectively, on two separate study days in 5 healthy volunteers, to ensure an appropriate dose is applied in the main study.

Conditions

Headache

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Dose Riociguat 2,5 or 5mg

Riociguat dose finding pilot experiment, 2,5mg and 5mg

Group Type: EXPERIMENTAL

Dose Riociguat 2,5 or 5mg

Intervention Type: DRUG

A selective stimulator of soluble guanylate cyclase (sGC)

Riociguat

Riociguat orally

Group Type: ACTIVE_COMPARATOR

Riociguat

Intervention Type: DRUG

A selective stimulator of soluble guanylate cyclase (sGC)

Placebo

Placebo orally

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Dose Riociguat 2,5 or 5mg

A selective stimulator of soluble guanylate cyclase (sGC)

Intervention Type: DRUG

Riociguat

A selective stimulator of soluble guanylate cyclase (sGC)

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Ability to provide written informed consent and receive participant privacy and rights information.
• Male or female participants aged 18-45 years.
• Weight between 50-100kg
• Non-smokers

Exclusion Criteria

• Any current or previous known primary or secondary headache disorder(s) apart from tension type headache ≤ 1 day per month.
• Headache <48 hours before study start.
• Daily use of any medication except contraceptives. Specifically use of nitrates or nitric oxide donors or phosphodiesterase inhibitors.
• Intake of any pro necessitate medication later than 4 times plasma half-life for the specific drug before study start, except for contraceptives
• 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 urin screening on screening day or study days.
• A medical history or clinical signs of

• Hypertension (systolic blood pressure >140mmHg and/or diastolic blood pressure >90mmHg)
• 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.
• Blood work at screening with signs of anemia.
• Blood work at screening with signs of abnormal kidney and liver function.
• A medical history or clinical signs of cardiovascular disease including cerebrovascular disease.
• A medical history or clinical signs of pulmonary disease.
• A medical history or clinical signs of liver, renal, gastrointestinal, endocrine, hematological or neurological disease.
• A medical history or clinical signs of psychiatric illness or substance abuse
• A medical history or clinical signs of drug or alcohol abuse
• A medical history or clinical signs of disease of any origin that the investigative doctor finds relevant for participation in the study
• A family history of severe cardiac disease.
• Any history of hypersensitivity to riociguat.
• Subjects who do not want information about crucial pathological findings during the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Danish Headache Center

OTHER

Sponsor Role: lead

Responsible Party

Messoud Ashina, MD

MD, Ph.D., DMSc., Chief Consultant Neurologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Messoud Ashina, MD

Role: PRINCIPAL_INVESTIGATOR

Danish Headache Center

Locations

Danish Headache Center

Copenhagen, Glostrup, Denmark

Countries

Denmark

Other Identifiers

H-22020347

Identifier Type: -

Identifier Source: org_study_id