Neurologic Signatures of Chronic Pain Disorders

October 28, 2020 updated by: Taipei Veterans General Hospital, Taiwan

"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. Identification of common and disease-specific brain signatures for chronic pain (sub-projects A, B, C)
  2. Investigation of clinical indicators with predictive values by machine learning analysis of big data (sub-projects A, B, C)
  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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

200

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan, 112
        • Headache Center, Teipei Veterans General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: patients with chronic migraine
flunarizine for patients with chronic migraine
Drug: flunarizine and/or pregabalin
Experimental: patients with fibromyalgia
pregabalin for patients with fibromyalgia
Drug: flunarizine and/or pregabalin
Experimental: patients with chronic migraine and fibromyalgia
flunarizine and pregabalin for patients with chronic migraine and myalgia
Drug: flunarizine and/or pregabalin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
clinical improvement after treatment (1) headache/pain intensity [NRS, numeric rating scale]
Time Frame: 4 months
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]
Time Frame: 4 months
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]
Time Frame: 4 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
EEG change after treatment
Time Frame: 4 months

Linear and nonlinear analysis of EEG before and after treatment

  • Three EEG session will be arranged. The first one is done before treatment, and the 2nd/3rd one will be done after a 2-month/4-month treatment course, respectively.
  • The EEG analyses include linear (eg: power spectrum, coherence, functional connectivity) analyses as well as non-linear (eg: entropy) analyses.
4 months
sensory and pain threshold change after treatment
Time Frame: 2 months

Using quantitative sensory testing (QST) to evaluate the sensory and pain threshold before and after treatment

  • Three QST session will be arranged. The first one is done before treatment, and the 2nd/3rd one will be done after a 2-month/4-month treatment course, respectively.
  • Equipment: electric von Fray filaments
  • unit: gram
2 months
Autonomic function change after treatment
Time Frame: 2 months

Using heart rate variability (HRV) to evaluate autonomic function before and after treatment

  • Three HRV session will be arranged. The first one is done before treatment, and the 2nd/3rd one will be done after a 2-month/4-month treatment course, respectively.
  • The HRV analyses include time-domain (eg: mean heart rate and its variation, mean R-R interval and its variation), and also frequency domain analysis (eg: power spectrum)
2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taipei Veterans General Hospital, Taiwan

Collaborators

Ministry of Science and Technology, R.O.C.

Investigators

  • Principal Investigator: Shuu-Jiun Wang, M.D., Neurological Institute, Taipei Veterans General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Actual)

December 1, 2019

Study Registration Dates

First Submitted

April 1, 2016

First Submitted That Met QC Criteria

April 19, 2016

First Posted (Estimate)

April 22, 2016

Study Record Updates

Last Update Posted (Actual)

November 2, 2020

Last Update Submitted That Met QC Criteria

October 28, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015-10-001BC2015-11-001AC002B

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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