Decoding Pain Sensitivity in Migraine With Multimodal Brainstem-based Neurosignature

NCT04702971 | Unknown Phase 4

• 1 other identifier: 2020-11-004C
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

Migraine is a highly prevalent and disabling neurological disease, which has a tremendous impact on sufferers, healthcare systems, and the economy. According to the 2016 WHO report, migraine is the second leading cause of years lived with disability, greater than all other neurological diseases combined. Yet, the treatment in migraine is far from optimum; the sufferers often abuse painkillers and complicated with medication overuse headache. Migraine is characterized by the hypersensitivity of the sensory system, potentially attributed to dysfunctional pain modulatory networks located in the deep brain structures, particularly the brainstem. However, the current understanding of these deeply seated, dysregulated pain modulatory circuits in migraine is limited due to technological constraints. Besides, studies with an in-depth analysis of the clinical manifestations (i.e., deep phenotyping) are lacking, and there is no corresponding animal model readily available for translational research. In this project, the investigators propose a multimodal approach to address these issues by applying the technologies and platforms developed by our team to explore the correlation between pain sensitivity and dysregulated connectivities from brainstem to other brain regions. In this four-year project, the investigators will recruit 400 migraine patients and 200 healthy subjects. The investigators aim at decomposing the key brainstem mechanisms underlying dysmodulated pain sensitivity in migraine from 5 comprehensive perspectives: (1) clinical deep phenotyping, (2) high-resolution brainstem structural MRI and functional connectivity analysis, (3) innovative brainstem EEG signal detecting technique, (4) multimodal data fusion platform with neural network analysis, and (5) ultrahigh-resolution brainstem-based connectomes, intravital manipulations and recording, and connectome-sequencing in animal models. Moreover, the investigators will collaborate with Taiwan Semiconductor Research Institute to develop a wearable high-density EEG equipment, integrated with a System-on-Chip capable of edge-computing the signal using algorithms derived from our brainstem decoding platform. The ultimate goal is to build a real-time brainstem decoding system for clinical application.

Conditions

Migraine

Outcome Measures

Primary Outcomes (3)

• Clinical change after treatment (1) headache frequency

  clinical change (headache frequency) after treatment unit: attacks per month analysis: comparing the mean headache frequency in each month after treatment (M1/M2/M3/M4/M5/M6) to that before treatment (M0)

  6 months

• Clinical change after treatment (2) headache intensity

  clinical change (headache intensity) after treatment unit: NRS (numeric rating scale, 0-10) analysis: comparing the mean headache intensity in each month after treatment (M1/M2/M3/M4/M5/M6) to that before treatment (M0)

  6 months

• Clinical change after treatment (3) headache duration

  clinical change (headache duration) after treatment unit: hours/day analysis: comparing the mean headache duration (hours/day) in each month after treatment (M1/M2/M3/M4/M5/M6) to that before treatment (M0)

  6 months

Secondary Outcomes (11)

• EEG change after treatment (1) Linear analysis of EEG before and after treatment

  12 months

• EEG change after treatment (2) Nonlinear analysis of EEG before and after treatment

  12 months

• EEG change after treatment (3) Nonlinear analysis of EEG before and after treatment

  12 months

• Sensory threshold change after treatment

  12 months

• fMRI change after treatment (1)

  12 months

Study Arms (2)

patients with migraine

EXPERIMENTAL

patient with migraine will be prescribed with flunarizine or routine clinical care per clinician's decision based on the condition of each individual patient

Drug: Flunarizine

healthy control

OTHER

healthy control

Other: healthy control

Interventions

Flunarizine DRUG

The flunarizine will be given per clinical routine

patients with migraine

healthy control OTHER

no intervention for healthy control

healthy control

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• fulfill the diagnostic criteria of migraine in ICHD-3,
• yrs,
• understand the study design and willing to join the study
• at least four headache days per month,
• the onset of headache is prior to 50 yrs.,
• normal neurological examination findings.

You may not qualify if:

• history or family history of epilepsy,
• taking migraine prophylactics,
• women who are breastfeeding or pregnant,
• severe psychological disorders, including major depression, PTSD, personality disorders, bipolar disorder, schizophrenia,
• medical, neurological or psychiatric disease discovered by the researcher that would hinder the research,
• contraindications for MR scan (pacemaker, claustrophobia, stent, metal implants…).
• Healthy:
• yrs,
• normal neurological examination findings,
• understand the study design and willing to join the study.
• history or family history of epilepsy,
• women who are breastfeeding or pregnant,
• severe psychological disorders, including major depression, PTSD, personality disorders, bipolar disorder, schizophrenia,
• medical, neurological or psychiatric disease discovered by the researcher that would hinder the research,
• contraindications for MR scan (pacemaker, claustrophobia, stent, metal implants…),

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan: lead

Study Sites (1)

Headache Center, Teipei Veterans General Hospital

Taipei, 112, Taiwan

RECRUITING

MeSH Terms

Conditions

Migraine Disorders

Interventions

Flunarizine

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Shuu-Jiun Wang

CONTACT

28712121; k123wang@gmail.com

Li-Ling Pan

CONTACT

hope881212@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: January 11, 2021
• Study Start: February 26, 2021
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: April 14, 2021

Record last verified: 2021-04

Locations

TW (1)