Investigation of Plastic Changes in the CNS Associated With Peripheral Neuropathy
Primary Purpose
Peripheral Neuropathy
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Moderate heat pain
Sponsored by
About this trial
This is an interventional basic science trial for Peripheral Neuropathy
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of a peripheral nerve disease - IPN, CIDP or CMT1A (patient group only)
- Healthy volunteers with no history of medical conditions known to afflict the nervous system will be recruited as normal controls (control group only)
- Age 18-60 (Inclusive)
- Able to undergo PET and MRI
- Patients who are not on sedative, antidepressant, sedative antihistaminic or narcotic medications.
Exclusion Criteria:
- Any subject unwilling to undergo genetic testing (DNA sampling)
- Any subjects with history of conditions known to affect the PNS, such as diabetes, stroke, thyroid disease, chemotherapy, renal failure, alcohol abuse, etc.
- Subjects with abnormal physical findings suggesting peripheral nerve diseases.
- 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
Sites / Locations
Outcomes
Primary Outcome Measures
Regional brain glucose metabolic changes
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.
Nerve conduction assessment
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.
Pain Scale Assessment
Neuropathy Pain Scale (NPS) instrument. Units is a score between 0 (no pain) and 100 (worst possible pain).
Secondary Outcome Measures
Full Information
NCT ID
NCT03805893
First Posted
January 8, 2019
Last Updated
January 12, 2019
Sponsor
Wayne State University
1. Study Identification
Unique Protocol Identification Number
NCT03805893
Brief Title
Investigation of Plastic Changes in the CNS Associated With Peripheral Neuropathy
Official Title
Investigation of Plastic Changes in the CNS Associated With Peripheral Neuropathy
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
February 1, 2019 (Anticipated)
Primary Completion Date
November 30, 2020 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wayne State University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Neuropathy
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Two groups: patients with peripheral neuropathy and normal controls
Masking
None (Open Label)
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Procedure
Intervention Name(s)
Moderate heat pain
Intervention Description
To apply a sensory challenge that can be applied over longer periods required for PET imaging and that is also compatible with high magnetic fields during MRI scanning, we will use a well-established thermal challenge of the lower extremity. To apply mildly painful heat to the patient, the right leg (from the foot up to the knee) will be wrapped in a blanket that incorporates a network of small-diameter plastic tubing through which hot water (45 - 55 oC) is circulated from a temperature-controlled reservoir.
Primary Outcome Measure Information:
Title
Regional brain glucose metabolic changes
Description
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.
Time Frame
Day 0
Title
Nerve conduction assessment
Description
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.
Time Frame
Day 0
Title
Pain Scale Assessment
Description
Neuropathy Pain Scale (NPS) instrument. Units is a score between 0 (no pain) and 100 (worst possible pain).
Time Frame
Day 0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Diagnosis of a peripheral nerve disease - IPN, CIDP or CMT1A (patient group only)
Healthy volunteers with no history of medical conditions known to afflict the nervous system will be recruited as normal controls (control group only)
Age 18-60 (Inclusive)
Able to undergo PET and MRI
Patients who are not on sedative, antidepressant, sedative antihistaminic or narcotic medications.
Exclusion Criteria:
Any subject unwilling to undergo genetic testing (DNA sampling)
Any subjects with history of conditions known to affect the PNS, such as diabetes, stroke, thyroid disease, chemotherapy, renal failure, alcohol abuse, etc.
Subjects with abnormal physical findings suggesting peripheral nerve diseases.
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
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Results of the study will be published in international journals.
Learn more about this trial
Investigation of Plastic Changes in the CNS Associated With Peripheral Neuropathy
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