Neurophysiology of Prophylactic Treatment in Migraine

Neurophysiological Characterization of Treatment Response Following the Initiation of Prophylactic Therapy in Episodic Migraine

This study aims to improve the pathophysiological understanding of migraine in in a longitudinal observational study investigating changes of established neurophysiological and imaging parameters in line with changes of the clinical phenotype.

The study's focus is the investigation of mechanisms that are directly related to the cyclic character of migraine and its core structures. In this context, the primary endpoint is a change in the nociceptive blink reflex, an established brain stem reflex to study the trigemino-spinal system, associated with changes in migraine frequency and severity. In order to reliably detect changes in the trigeminal pain system, investigations are performed in patients before starting a prophylactic therapy and 3 months afterwards. Several secondary endpoints are used to evaluate changes of multimodal sensory and cortical information processing. Cerebral imaging will include examinations of structural and network effects of altered migraine disease activity.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: antibodies against calcitonin-gene related peptide or its receptor

• Study Type: Observational
• Enrollment (Actual): 44

Contacts and Locations

Study Locations

• Germany
  • Mecklenburg-Vorpommern
    • Greifswald, Mecklenburg-Vorpommern, Germany, 17475
      • Department of Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patients seen in the local headache clinic are screened for eligibility to participate the study. Clinical routine is not influenced by participation in this observational study, importantly choice of prophylactic treatment solely depends on the physician's and patient's decision based on national guidelines.

Description

Inclusion Criteria (migraineurs):

• episodic migraine according to ICHD (international classification of headache disorders)-3 criteria
• headache documented over at least 3 months through a headache calender
• scheduled for prophylactic therapy of their migraine

Exclusion Criteria (migraineurs):

• history of chronic migraine
• current medication-overuse headache
• neurological or psychiatric diagnosis other than headaches
• chronic intake of central nervous system active drugs (antidepressants, antipsychotics etc.)
• contraindications for magnetic resonance imaging
• contraindications for transcranial magnetic stimulation

Inclusion criteria (controls):

• not more than 3 years younger or older than matched control
• gender similar to matched control
• menstrual cycle equal to matched control (if female)

exclusion criteria (controls):

• more than 1 headache day/month
• history of migraine

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Episodic Migraine	Drug: antibodies against calcitonin-gene related peptide or its receptor; the study is observational and does not interfere with clinical routine. In lin with this notion, the intervention is chosen by the treating physician in a shared decision making process involving the patient
Healthy controls; equal to or less than 1 headache day/month

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
nociceptive blink reflex habituation	habituation of the area under of the curve of the R2 blink reflex component on the side primarily affected by migraine headaches	baseline and after 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
nociceptive blink reflex area	area under of the curve of the R2 blink reflex component on the side primarily affected by migraine headaches	baseline and after 3 months
somatosensory evoked potentials (SSEP)	habituation of the N20 SSEP component following bilateral median nerve stimulation	baseline and after 3 months
pattern-reversal visual evoked potentials (VEP)	habituation of the P100 VEP component following bilateral optic nerve stimulation	baseline and after 3 months
migraine headache frequency	days with migraine headaches during the last month	baseline and after 3 months
headache impact test (HIT-6)	impact of migraine severity on daily routine	baseline and after 3 months
migraine disability assessment (MIDAS)	impact of migraine frequency on daily routine	baseline and after 3 months
Patient-Reported Outcomes Measurement Information System Profile 29 (PROMIS-29)	multi domain patient reported quality of life	baseline and after 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
transcranial magnetic stimulation (TMS)	input-output curves of motor evoked potential following single and double-pulse navigated TMS to the side stimulated during the nociceptive blink reflex examination	baseline and after 3 months
electroencephalography (EEG)	EEG connectivity following nociceptive and sensory stimulation	baseline and after 3 months
structural magnetic resonance imaging (sMRI)	volumetry of brain structures involved in central pain processing (e.g. cingulate cortex, insula, thalamus)	baseline and after 3 months
functional magnetic resonance imaging (fMRI)	resting-state connectivity of networks involved in central pain processing	baseline and after 3 months

Collaborators and Investigators

• Sponsor: University Medicine Greifswald

Publications and helpful links

General Publications

• Thiele A, Klehr L, Strauss S, Angermaier A, Schminke U, Kronenbuerger M, Naegel S, Fleischmann R. Preventive treatment with CGRP monoclonal antibodies restores brain stem habituation deficits and excitability to painful stimuli in migraine: results from a prospective case-control study. J Headache Pain. 2021 Dec 11;22(1):149. doi: 10.1186/s10194-021-01364-x.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 29, 2019
• Primary Completion (ACTUAL): May 2, 2021
• Study Completion (ACTUAL): May 2, 2021

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 10, 2019
• First Posted (ACTUAL): July 15, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 27, 2021
• Last Update Submitted That Met QC Criteria: May 26, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: functional magnetic resonance imaging; electroencephalography; evoked potentials; blink reflex
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Vasodilator Agents; Immunologic Factors; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antibodies; Calcitonin; Salmon calcitonin; Calcitonin Gene-Related Peptide; Katacalcin
• Other Study ID Numbers: BB168/18

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No