CGRP Inhibition, Autonomic Function, and Migraine

NCT04628429 | Recruiting FDA Drug

• 1 other identifier: EK Nr:1910/2020
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical study is to better understand the function of the autonomic nervous system in patients with migraine. We aim to understand whether the autonomic functions change depending on the migraine status (i.e. whether they are between or during attacks) and whether the CGRP monoclonal antibody (mAb) class of drugs affects the autonomic functions. The aim is not to investigate the effect of CGRP-mAb on migraine frequency. Calcitonin gene-related peptide (CGRP) is a neurotransmitter in the nervous system that plays an essential role in the development of migraine headache. Monoclonal antibodies can block the function of this messenger substance. Several studies have shown that this blockade leads to a reduction in the frequency of migraine. In addition to its role in migraine, CGRP also acts on the blood vessels and the autonomic nervous system. The autonomic nervous system is responsible for everything we have no control over in our body. This includes everything from heart rate and blood pressure to our digestion.

Conditions

Episodic Migraine; Chronic Migraine

Keywords

Calcitonin gene-related peptide inhibition; Monoclonal antibodies; Autonomic function; Composite Autonomic Symptom Scale 31; Migraine Disability Assessment Scale; Depression Anxiety Stress Scales; Cardiovascular Autonomic Dysfunction; Headache Impact Questionnaire

Outcome Measures

Primary Outcomes (3)

• Change from Day 0 Cardiovagal Autonomic Dysfunction (CAD) at 5 months

  It is derived from the Composite Autonomic severity scale (CASS), an "unbiased and full quantification" of the autonomic functions in the cardiovagal, adrenergic and sudomotor domain. The total CASS score has "a direct clinical meaning since it ranks the generalized dysautonomia as mild, moderate and severe". By isolating two of the indices of the CASS - adrenergic index (AI) and cardiovagal index (CI) - one can quantify the Cardiovascular Autonomic Dysfunction (CAD). Results are referred to as normal (CAD total score = 0) or abnormal. Abnormal values are considered 1-7, indicating presence of CAD.

  Day 0, Month 5 (EOS)

• Change from Days 1-31 Cardiovagal Autonomic Dysfunction (CAD) at 5 months

  It is derived from the Composite Autonomic severity scale (CASS), an "unbiased and full quantification" of the autonomic functions in the cardiovagal, adrenergic and sudomotor domain. The total CASS score has "a direct clinical meaning since it ranks the generalized dysautonomia as mild, moderate and severe". By isolating two of the indices of the CASS - adrenergic index (AI) and cardiovagal index (CI) - one can quantify the Cardiovascular Autonomic Dysfunction (CAD). Results are referred to as normal (CAD total score = 0) or abnormal. Abnormal values are considered 1-7, indicating presence of CAD.

  Days 1-31, Month 5 (EOS)

• Change from Days 0 Cardiovagal Autonomic Dysfunction (CAD) at Days 1-31

  It is derived from the Composite Autonomic severity scale (CASS), an "unbiased and full quantification" of the autonomic functions in the cardiovagal, adrenergic and sudomotor domain. The total CASS score has "a direct clinical meaning since it ranks the generalized dysautonomia as mild, moderate and severe". By isolating two of the indices of the CASS - adrenergic index (AI) and cardiovagal index (CI) - one can quantify the Cardiovascular Autonomic Dysfunction (CAD). Results are referred to as normal (CAD total score = 0) or abnormal. Abnormal values are considered 1-7, indicating presence of CAD.

  Day 0, Days 1-31

Secondary Outcomes (5)

• Change from Days 0 Composite Autonomic Symptom Scale 31 (COMPASS-31) at 5 months

  Day 0, Month 5 (EOS)

• Change from Days 0 Day Impact Questionnaire (HIQ) at 5 months

  Day 0, Month 5 (EOS)

• Change from Days 0 Non-Headache Day Impact Questionnaire (Non-HIQ) at 5 months

  Day 0, Month 5 (EOS)

• Change from Days 0 Migraine Disability Assessment Scale (MIDAS) at 5 months

  Day 0, Month 5 (EOS)

• Change from Days 0 Depression Anxiety Stress Scale (DASS) at 5 months

  Day 0, Month 5 (EOS)

Study Arms (3)

Episodic Migraine

All patients who have been diagnosed with migraine without aura or migraine with aura according to the diagnostic criteria of the International Classification of Headache Disorders, third edition (ICHD-3) and have been unsuccessfully treated with first-line prophylactic medication

Drug: Erenumab; Drug: Galcanezumab; Drug: Fremanezumab

Chronic Migraine

All patients who have been diagnosed with chronic migraine (≥15 headache days per month 8 of which with migrainous features) according to the diagnostic criteria of the International Classification of Headache Disorders, third edition (ICHD-3) and have been unsuccessfully treated with first-line prophylactic medication

Drug: Erenumab; Drug: Galcanezumab; Drug: Fremanezumab

Healthy Control

Controls must be healthy (free of any diagnosed chronic disease, acute infection requiring medication, family history or personal history of migraine), chosen to be as similar as possible to migraine patients, in terms of age and sex.

Interventions

Erenumab DRUG

anti-CGRP-receptor monoclonal anti-body

Also known as: Aimovig®

Chronic Migraine; Episodic Migraine

Galcanezumab DRUG

anti-CGRP-ligand monoclonal anti-body

Also known as: Emgality®

Chronic Migraine; Episodic Migraine

Fremanezumab DRUG

anti-CGRP-ligand monoclonal anti-body

Also known as: Ajovy®

Chronic Migraine; Episodic Migraine

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed to be suffering from migraine without aura, migraine with aura or chronic migraine according to the diagnostic criteria of the International Classification of Headache Disorders, third edition (ICHD-3). Patients will be ages 18 to 64. It is mandatory they have valid health insurance provided by one of the insurance institutions of Austria. Controls must be healthy (free of any diagnosed chronic disease or acute infection requiring medication), chosen to be as similar as possible to migraine patients, in terms of age and sex

You may qualify if:

• Chronic migraine according to ICHD-3
• Episodic migraine without aura or with aura according to ICHD-3
• Unsuccessful treatment with 3 or more established prophylactic drugs
• Medicine costs are covered by health insurance
• Healthy controls must be free from any diagnosed chronic disease or acute infection requiring medication

You may not qualify if:

• Pregnancy and lactation
• Neurosurgical interventions performed within the last 12 months
• Coronary bypass surgery or revascularization procedures performed within the last 12 months
• History of transient ischemic attacks (TIA), stroke, stable or unstable angina pectoris, myocardial infarction or uncontrolled hypertension
• Known hypersensitivity to therapy with an anti-CGRP Antibodies
• History of a disorder (other than migraine) that may affect the results of autonomic tests
• Healthy controls must have no personal or family history of migraine

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, 1090, Austria

RECRUITING

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MeSH Terms

Interventions

erenumab; galcanezumab; fremanezumab

Study Officials

• Christian Wöber, Prof. MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antun R Pavelic, MD

CONTACT

+43 (0)1 40400 - 31170; antun.pavelic@meduniwien.ac.at

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 13, 2020
• Study Start: October 1, 2020
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)