NCT02747940

Brief Summary

"Brain signatures" as objective measures of acute pain have been characterized with functional magnetic resonance image and machine learning technology. As compared to acute pain, chronic pain leads to greater socioeconomic burden. However, measures for chronic pain remain subjective and suboptimal, and the brain signatures for chronic pain are largely unknown. Chronic migraine and fibromyalgia are two prototypes primary chronic pain disorders with high disability and intractability with prevalence of around 2% for both diseases. These two chronic pain disorders have shared clinical presentations (abnormal pain sensitivity, mood and sleep disorders), pathophysiology (central sensitization) and medical treatment (anti-depressants), despite different body parts are involved (head vs. whole body). The present integrated project aims to characterize both common and disease-specific brain signatures of chronic pain by investigating these two chronic pain disorders. Our findings may shed some light on the key mechanisms of pain chronification, and may pave the way for the optimization of diagnosis and prognostication, as well as formulation of personalized medicine in chronic pain, so as to improve life quality of these patients and to reduce socioeconomic loss. The present project includes three interdisciplinary sub-projects (plus one animal study, not listed here): A: Clinical studies for chronic migraine and fibromyalgia: endophenotypes and pain chronification B: Functional neuroimaging of chronic pain: multimodal quantitative analysis of brain connectomes C. Data stream mining technology for multimodal physiological signals of chronic pain: real-time tracking and clinical correlation The specific aims of the present projects include:

  1. 1.Identification of common and disease-specific brain signatures for chronic pain (sub-projects A, B, C)
  2. 2.Investigation of clinical indicators with predictive values by machine learning analysis of big data (sub-projects A, B, C)
  3. 3.Elucidation of the specific anatomical structures or neural networks underpinning pain chronification based on clinical neuroimaging (sub-projects A, B) In this 1st-year pilot study of the 4-year longitudinal study, we will establish experimental platforms for each sub-project, start to recruit participants and perform endophenotyping, as well as have a preliminary integration for sub-projects A, B and C.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for phase_4 chronic-pain

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2015

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

April 1, 2016

Completed
21 days until next milestone

First Posted

Study publicly available on registry

April 22, 2016

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2019

Completed
Last Updated

November 2, 2020

Status Verified

October 1, 2020

Enrollment Period

4 years

First QC Date

April 1, 2016

Last Update Submit

October 28, 2020

Conditions

Outcome Measures

Primary Outcomes (3)

  • clinical improvement after treatment (1) headache/pain intensity [NRS, numeric rating scale]

    clinical improvement (headache/pain intensity) after treatment unit: NRS (numeric rating scale, 0-10) analysis: comparing the mean headache/pain intensity in each month after treatment (M1/M2/M3/M4) to that before treatment (M-1)

    4 months

  • clinical improvement after treatment (2) headache/pain frequency [attacks per month]

    clinical improvement (headache/pain frequency) after treatment unit: attacks per month analysis: comparing the mean headache/pain frequency in each month after treatment (M1/M2/M3/M4) to that before treatment (M-1)

    4 months

  • clinical improvement after treatment (3) headache/pain duration [hours per day]

    clinical improvement (headache/pain duration) after treatment unit: hours/day analysis: comparing the mean headache/pain duration (hours/day) in each month after treatment (M1/M2/M3/M4) to that before treatment (M-1)

    4 months

Secondary Outcomes (3)

  • EEG change after treatment

    4 months

  • sensory and pain threshold change after treatment

    2 months

  • Autonomic function change after treatment

    2 months

Study Arms (3)

patients with chronic migraine

EXPERIMENTAL

flunarizine for patients with chronic migraine

Drug: flunarizine and/or pregabalin

patients with fibromyalgia

EXPERIMENTAL

pregabalin for patients with fibromyalgia

Drug: flunarizine and/or pregabalin

patients with chronic migraine and fibromyalgia

EXPERIMENTAL

flunarizine and pregabalin for patients with chronic migraine and myalgia

Drug: flunarizine and/or pregabalin

Interventions

patients with chronic migrainepatients with chronic migraine and fibromyalgiapatients with fibromyalgia

Eligibility Criteria

Age20 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Control: devoid of any systemic or neurological diseases
  • Chronic migraine: by ICHD-III (International Classification of Headache Disorder) criteria
  • Fibromyalgia: by ACR (American College of Rheumatology) 2010 criteria

You may not qualify if:

  • history of major systemic illness, including uncontrolled hypertension, diabetes, chronic renal insufficiency, autoimmune diseases or malignancies
  • history of neurological disorders which might affect sensation such as previous stroke or peripheral neuropathy
  • history of substance abuse (except painkillers)
  • heavy smokers (with a daily consumption \>20 cigarettes)
  • pregnancy or lactation
  • any contraindication for magnetic resonance imaging (MRI)
  • and any obvious infection or inflammation over a period of at least 1 month before the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Headache Center, Teipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Related Publications (5)

  • Chuang CH, Li JY, King JT, Chen WT, Chen SP, Wang YF, Liu HY, Hsiao FJ, Pan LH, Wang SJ, Lai KL. Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study. Cephalalgia. 2023 Oct;43(10):3331024231206781. doi: 10.1177/03331024231206781.

  • Pan LH, Chen WT, Wang YF, Chen SP, Lai KL, Liu HY, Hsiao FJ, Wang SJ. Resting-state occipital alpha power is associated with treatment outcome in patients with chronic migraine. Pain. 2022 Jul 1;163(7):1324-1334. doi: 10.1097/j.pain.0000000000002516. Epub 2021 Oct 13.

  • Pan LH, Wang YF, Ling YH, Lai KL, Chen SP, Chen WT, Treede RD, Wang SJ. Pain sensitivities predict prophylactic treatment outcomes of flunarizine in chronic migraine patients: A prospective study. Cephalalgia. 2022 Aug;42(9):899-909. doi: 10.1177/03331024221080572. Epub 2022 Apr 11.

  • Hsiao FJ, Chen WT, Liu HY, Wang YF, Chen SP, Lai KL, Hope Pan LL, Coppola G, Wang SJ. Migraine chronification is associated with beta-band connectivity within the pain-related cortical regions: a magnetoencephalographic study. Pain. 2021 Oct 1;162(10):2590-2598. doi: 10.1097/j.pain.0000000000002255.

  • Hsiao FJ, Chen WT, Ko YC, Liu HY, Wang YF, Chen SP, Lai KL, Lin HY, Coppola G, Wang SJ. Neuromagnetic Amygdala Response to Pain-Related Fear as a Brain Signature of Fibromyalgia. Pain Ther. 2020 Dec;9(2):765-781. doi: 10.1007/s40122-020-00206-z. Epub 2020 Oct 22.

MeSH Terms

Conditions

Chronic PainFibromyalgia

Condition Hierarchy (Ancestors)

PainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsMuscular DiseasesMusculoskeletal DiseasesRheumatic DiseasesNeuromuscular DiseasesNervous System Diseases

Study Officials

  • Shuu-Jiun Wang, M.D.

    Neurological Institute, Taipei Veterans General Hospital

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

April 1, 2016

First Posted

April 22, 2016

Study Start

December 1, 2015

Primary Completion

December 1, 2019

Last Updated

November 2, 2020

Record last verified: 2020-10

Data Sharing

IPD Sharing
Will not share

Locations