MigraineMiPro-CGRPNCT04796766
Human Electrophysiological Model to Quantify the CGRP-related Axon Reflex of Trigeminal Afferents
A study testing High frequency stimulation (HFS) and Low-frequency sinusoidal transcutaneous stimulation (sLFS) in people with Migraine, run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
The proposed project aims at establishing Calcitonin gene-related peptide (CGRP)-Related Axon Reflex of Trigeminal Afferents as a neurophysiological biomarker for migraine. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Migraine
- What is being tested?
- High frequency stimulation (HFS) and Low-frequency sinusoidal transcutaneous stimulation (sLFS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteGermany
- Study dates
- 1 Feb 2021to Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
The proposed project aims at establishing Calcitonin gene-related peptide (CGRP)-Related Axon Reflex of Trigeminal Afferents as a neurophysiological biomarker for migraine.
Read the 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.
- Conditions
- Migraine
- Being tested
- High frequency stimulation (HFS), Low-frequency sinusoidal transcutaneous stimulation (sLFS)
- Keywords
- Migraine, Calcitonin gene-related peptide (CGRP), Evoked flare response
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High frequency stimulation (HFS)Diagnostic test
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.
Low-frequency sinusoidal transcutaneous stimulation (sLFS)Diagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| Healthy volunteers | Experimental | HFS / LFS in healthy volunteers at two different points in time Receives: Diagnostic Test: High frequency stimulation (HFS); Diagnostic Test: Low-frequency sinusoidal transcutaneous stimulation (sLFS) |
| Migraine patients | Experimental | HFS / LFS in migraine patients at a single point in time Receives: Diagnostic Test: High frequency stimulation (HFS); Diagnostic Test: Low-frequency sinusoidal transcutaneous stimulation (sLFS) |
| Patients with Botulinum toxin or CGRP-targeted therapy | Experimental | HFS / LFS before and under treatment with Botulinum toxin or CGRP-targeted therapy Receives: Diagnostic Test: High frequency stimulation (HFS); Diagnostic Test: Low-frequency sinusoidal transcutaneous stimulation (sLFS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intensity of axonal flare reaction
Axon reflex erythema of stimulated C-nociceptors measured in Flux (luminous flux) values 0 - 100.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2021
- Study start1 Feb 2021
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MigraineStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sigrid Schuh-Hofer, Prof. Dr., Principal investigator, University Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04796766
- Sponsor's protocol ID
- MiPro-CGRP
- Acronym
- MiPro-CGRP
- Status last verified
- Dec 2023
- First submitted
- 1 Mar 2021
- Last updated
- 15 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04796766
- Acronym / sponsor ID
- MiPro-CGRP / MiPro-CGRP
- Conditions
- Migraine
- Keywords
- Migraine, Calcitonin gene-related peptide (CGRP), Evoked flare response
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 15 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers | Experimental | Diagnostic Test: High frequency stimulation (HFS), Diagnostic Test: Low-frequency sinusoidal transcutaneous stimulation (sLFS)HFS / LFS in healthy volunteers at two different points in time |
| Migraine patients | Experimental | Diagnostic Test: High frequency stimulation (HFS), Diagnostic Test: Low-frequency sinusoidal transcutaneous stimulation (sLFS)HFS / LFS in migraine patients at a single point in time |
| Patients with Botulinum toxin or CGRP-targeted therapy | Experimental | Diagnostic Test: High frequency stimulation (HFS), Diagnostic Test: Low-frequency sinusoidal transcutaneous stimulation (sLFS)HFS / LFS before and under treatment with Botulinum toxin or CGRP-targeted therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High frequency stimulation (HFS)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. | Diagnostic test | Healthy volunteers, Migraine patients, Patients with Botulinum toxin or CGRP-targeted therapy |
| Low-frequency sinusoidal transcutaneous stimulation (sLFS)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. | Diagnostic test | Healthy volunteers, Migraine patients, Patients with Botulinum toxin or CGRP-targeted therapy |
Primary outcome
Intensity of axonal flare reaction
Time frame: Day 1
Axon reflex erythema of stimulated C-nociceptors measured in Flux (luminous flux) values 0 - 100.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sigrid Schuh-Hofer, Prof. Dr. principal investigator
University Hospital Tuebingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High frequency stimulation (HFS) and Low-frequency sinusoidal transcutaneous stimulation (sLFS) in people with Migraine, run by University Hospital Tuebingen at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intensity of axonal flare reaction (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2023.