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Human Electrophysiological Model to Quantify the CGRP-related Axon Reflex of Trigeminal Afferents (MiPro-CGRP)

Primary Purpose

Migraine

Status

Active

Phase

Not Applicable

Locations

Germany

Study Type

Interventional

Intervention

High frequency stimulation (HFS)

Low-frequency sinusoidal transcutaneous stimulation (sLFS)

About this trial

This is an interventional basic science trial for Migraine focused on measuring Migraine, Calcitonin gene-related peptide (CGRP), Evoked flare response

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy volunteers (Study Arm 1 and 2):

age ≥ 18 years
good German language skills
no history of head trauma
no history of neurologic disease
no primary headache disorder (e.g. migraine, episodic or chronic tension type headache, cluster headache)
no regular drug intake (except for oral contraceptives)

Migraine patients need to match the following criteria (Study Arm 2 and 3):

age ≥ 18 years
good German language skills
fulfilling the diagnostic criteria for either episodic or chronic migraine with or without aura according to the international classification of headache disorders (ICHD) 3rd edition
history of migraine > 1 year
keeping a headache diary for a minimum of 3 months prior to the study

Exclusion Criteria:

Healthy volunteers and migraine patients under the following conditions will be excluded:

Chronic pain syndromes (e.g. low back pain, osteoarthritis, painful neuropathy, rheumatoid arthritis)
Acute pain (e.g. pain due to acute skin injury, menstrual pain, acute toothache). In this case, a measurement can only be performed after complete remission of pain and at least 48 hours after intake of acute pain medication (e.g. triptans, non-steroidal anti-inflammatory drug (NSAID)).
history of treatment with agents targeting the CGRP pathway (e.g. erenumab) < 3 months before the study
history of treatment with Botulinum toxin < 9 months before the study
Diseases of the skin involving the skin at face and forehead
Pregnancy or breast feeding
Subjects lacking capacity for consent

Sites / Locations

University Hospital Tübingen

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Healthy volunteers

Migraine patients

Patients with Botulinum toxin or CGRP-targeted therapy

Arm Description

HFS / LFS in healthy volunteers at two different points in time

HFS / LFS in migraine patients at a single point in time

HFS / LFS before and under treatment with Botulinum toxin or CGRP-targeted therapy

Outcomes

Primary Outcome Measures

Intensity of axonal flare reaction

Axon reflex erythema of stimulated C-nociceptors measured in Flux (luminous flux) values 0 - 100.

Secondary Outcome Measures

Full Information

NCT ID

NCT04796766

First Posted

March 1, 2021

Last Updated

May 17, 2022

Sponsor

University Hospital Tuebingen

1. Study Identification

Unique Protocol Identification Number

NCT04796766

Brief Title

Human Electrophysiological Model to Quantify the CGRP-related Axon Reflex of Trigeminal Afferents

Acronym

MiPro-CGRP

Official Title

Establishment of a Human Electrophysiological Model to Quantify the Calcitonin Gene-related Peptide (CGRP)-Related Axon Reflex of Trigeminal Afferents and Its Evaluation as a Clinical Tool to Assess and Predict Treatment Effects of Migraine Prophylaxis

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 1, 2021 (Actual)

Primary Completion Date

February 2023 (Anticipated)

Study Completion Date

February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital Tuebingen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The proposed project aims at establishing Calcitonin gene-related peptide (CGRP)-Related Axon Reflex of Trigeminal Afferents as a neurophysiological biomarker for migraine.

Detailed Description

The proposed project aims at establishing a neurophysiological biomarker for migraine. Migraine is one of the world's most disabling diseases and its prophylactic treatment is time and cost-consuming. Since each patient responds differently and unpredictably to preventive medication, physicians are forced to try prophylactic drugs one by one. Recently, a new group of therapeutic agents targeting the neuropeptide Calcitonin gene-related peptide (CGRP) has been launched for migraine treatment. CGRP is stored in trigeminal afferents and released to meningeal blood vessels during acute migraine attacks leading to a vasodilating response. In an experimental setting, the release of CGRP from afferent nerve fibers in the skin can be induced by transdermal electrical stimulation. The subsequently evoked skin erythema, called 'flare reaction', can be quantified by laser Doppler imaging techniques. Never before, research studies used this experimental model in either trigeminally innervated skin or migraine patients. I therefore propose to establish this model to 1) test the specificity of an evoked 'flare response' in the trigeminal territory for the pathophysiology of migraine, 2) investigate the effect of CGRP-targeting anti-migraine drugs on this outcome parameter and 3) evaluate the impact of this model to predict the treatment response to drugs interfering with the CGRP-pathway. This study is a highly innovative approach towards tailored migraine treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Migraine

Keywords

Migraine, Calcitonin gene-related peptide (CGRP), Evoked flare response

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Healthy volunteers

Arm Type

Experimental

Arm Description

HFS / LFS in healthy volunteers at two different points in time

Arm Title

Migraine patients

Arm Type

Experimental

Arm Description

HFS / LFS in migraine patients at a single point in time

Arm Title

Patients with Botulinum toxin or CGRP-targeted therapy

Arm Type

Experimental

Arm Description

HFS / LFS before and under treatment with Botulinum toxin or CGRP-targeted therapy

Intervention Type

Diagnostic Test

Intervention Name(s)

High frequency stimulation (HFS)

Intervention Description

Electrical stimuli via circular electrode array. The electrode array serves as cathode placed above the eyebrow. A surface electrode (anode) will be placed on the temple. Electrical stimuli will be applied via a constant current stimulator. The stimulus intensity for the electrophysiological protocol is adjusted to the 10-fold of the detection threshold. A number of 5 electrical pulses (2 ms, 100 Hertz (Hz)), 10 second intervals.

Intervention Type

Diagnostic Test

Intervention Name(s)

Low-frequency sinusoidal transcutaneous stimulation (sLFS)

Intervention Description

Stimulation of C-nociceptors with constant current stimulator. Electrodes (placed on the proband's forehead. Stimulation by sine wave pulses of 250 ms duration (4 Hz), intensities inducing a pain intensity of 50/100 on a visual analogue scale from 0-100.

Primary Outcome Measure Information:

Title

Intensity of axonal flare reaction

Description

Axon reflex erythema of stimulated C-nociceptors measured in Flux (luminous flux) values 0 - 100.

Time Frame

Day 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy volunteers (Study Arm 1 and 2): age ≥ 18 years good German language skills no history of head trauma no history of neurologic disease no primary headache disorder (e.g. migraine, episodic or chronic tension type headache, cluster headache) no regular drug intake (except for oral contraceptives) Migraine patients need to match the following criteria (Study Arm 2 and 3): age ≥ 18 years good German language skills fulfilling the diagnostic criteria for either episodic or chronic migraine with or without aura according to the international classification of headache disorders (ICHD) 3rd edition history of migraine > 1 year keeping a headache diary for a minimum of 3 months prior to the study Exclusion Criteria: Healthy volunteers and migraine patients under the following conditions will be excluded: Chronic pain syndromes (e.g. low back pain, osteoarthritis, painful neuropathy, rheumatoid arthritis) Acute pain (e.g. pain due to acute skin injury, menstrual pain, acute toothache). In this case, a measurement can only be performed after complete remission of pain and at least 48 hours after intake of acute pain medication (e.g. triptans, non-steroidal anti-inflammatory drug (NSAID)). history of treatment with agents targeting the CGRP pathway (e.g. erenumab) < 3 months before the study history of treatment with Botulinum toxin < 9 months before the study Diseases of the skin involving the skin at face and forehead Pregnancy or breast feeding Subjects lacking capacity for consent

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sigrid Schuh-Hofer, Prof. Dr.

Organizational Affiliation

University Hospital Tübingen

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Tübingen

City

Tübingen

ZIP/Postal Code

72076

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Human Electrophysiological Model to Quantify the CGRP-related Axon Reflex of Trigeminal Afferents

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