Investigation of Plastic Changes in the CNS Associated With Peripheral Neuropathy

January 12, 2019 updated by: Otto Muzik, Wayne State University
Recent neuroimaging literature on neuropathy suggests that chronic pain is characterized by learning-related and memory-related plastic changes of the central nervous system (CNS) with concomitant maladaptive changes in body perception. In particular, it is well accepted that learning-induced functional and structural brain changes involve, in addition to sensorimotor cortex, also limbic and frontal areas that mediate the transition from acute to chronic pain, resulting in pathological processing of body image, impaired multisensory integration and faulty feedback from various interoceptive processes. Interestingly, these alterations share many similarities with brain changes in emotional disorders and the specificity for pain needs to be determined. Moreover, the diagnosis and management of neuropathic pain syndromes remains a major clinical challenge, and this failure is partly attributed to our inability to identify functional brain changes that not only contribute to these syndromes, but also expose the patient to psychological burden that might lead to drug abuse. Although opioids are currently used frequently as first line therapy to alleviate pain caused by the various forms of neuropathies, recent reports indicate that long-term opioid therapy does not improve functional status but rather is associated with a higher risk of depression as well as subsequent opioid dependency and overdose. Thus, in order to improve therapeutic interventions in this patient group, it is imperative to develop a mechanistic model of central processes that could both explain and predict longitudinal changes associated with neuropathic pain syndromes. The identification of the correct sources of pain sensation (i.e. the contribution of central rather than peripheral factors to pain chronicity) is of paramount importance since the clinical course and patient management is likely to differ depending on the exact underlying cause.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The goal is to relate non-invasive brain imaging data to clinical parameters in order to develop a mechanistic model of CNS adaptive processes that are produced by a patient-specific disease state. The investigators believe that such a model will have significant predictive value and might provide added value for subsequent patient management. To achieve the stated objectives, the following Specific Aim will be tested:

Aim 1. To assess regional brain changes in patients with polyneuropathies associated with a mild thermal pain challenge and to relate these changes to clinical measures of neuropathy.

Hypothesis 1A. Regional changes in brain glucose metabolism (as measured using FDG PET/CT imaging) associated with thermal pain will differ between patients with polyneuropathy and a group of age-matched controls. Specifically, patients with neuropathy will show a significantly higher increase in glucose metabolism in the medial pain system (affective dimension - brainstem, amygdala, insula) following thermal pain as compared to the control group, indicating increased sensitivity of the interoceptive neural control system for peripheral pain stimulation in patients.

Hypothesis 1B. In patients with neuropathy, regional changes in brain glucose metabolism associated with thermal pain in the medial pain system (affective dimension - brainstem, amygdala, insula) will be inversely related to clinical measures of neuropathic disease state (as measured using quantitative sensory testing, nerve conduction study and standardized pain scale assessment). In contrast, glucose metabolic changes in the lateral pain system (discriminatory dimension - thalamus, area S1) will be directly related to clinical measures. The extent of changes in the medial versus lateral system will also be correlated with the types of polyneuropathies, including idiopathic painful sensory neuropathy, chronic inflammatory demyelinating polyneuropathy (CIDP) and Charcot-Marie-Tooth type-1A (CMT1A, the most common type of inherited peripheral nerve disease).

Hypothesis 1C. The increase in functional connectivity (as assessed using fMRI following an oscillatory thermal pain paradigm) will differ between neuropathic patients and controls. Specifically, functional connectivity between the medial pain system (brainstem, amygdala, insula) and the cognitive pain system (VLPFC and FP) will be significantly higher in the patient group as compared to the controls, indicating increased inhibition of the interoceptive brain network by the executive control system. Moreover, functional connectivity between the medial and cognitive pain systems will be directly related with clinical measures.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of a peripheral nerve disease - IPN, CIDP or CMT1A (patient group only)
  2. Healthy volunteers with no history of medical conditions known to afflict the nervous system will be recruited as normal controls (control group only)
  3. Age 18-60 (Inclusive)
  4. Able to undergo PET and MRI
  5. Patients who are not on sedative, antidepressant, sedative antihistaminic or narcotic medications.

Exclusion Criteria:

  1. Any subject unwilling to undergo genetic testing (DNA sampling)
  2. Any subjects with history of conditions known to affect the PNS, such as diabetes, stroke, thyroid disease, chemotherapy, renal failure, alcohol abuse, etc.
  3. Subjects with abnormal physical findings suggesting peripheral nerve diseases.
  4. Subjects of reproductive potential, who are sexually active but unwilling and/or unable to use medically appropriate contraception, or women who are pregnant or breastfeeding

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
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Regional brain glucose metabolic changes
Time Frame: Day 0
Changes in brain glucose metabolism associated with thermal pain in the brainstem, amygdala and insula regions. Units are the % change in regional standard uptake value (SUV) between the control and the thermal pain PET scan.
Day 0
Nerve conduction assessment
Time Frame: Day 0
Electromyography (EMG) study determining nerve conduction velocity (NCV). The unit of NCV is m/s. The lower the NCV values, the more severe is the neuropathy.
Day 0
Pain Scale Assessment
Time Frame: Day 0
Neuropathy Pain Scale (NPS) instrument. Units is a score between 0 (no pain) and 100 (worst possible pain).
Day 0

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Wayne State University

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 (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 8, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 16, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 16, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1811001903

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Results of the study will be published in international journals.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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