Ignite Creation Date:
2025-12-25 @ 1:24 AM
Ignite Modification Date:
2025-12-31 @ 2:30 PM
Study NCT ID:
NCT03805893
Status:
UNKNOWN
Last Update Posted:
2019-01-16
First Post:
2019-01-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Investigation of Plastic Changes in the CNS Associated With Peripheral Neuropathy
Sponsor:
Wayne State University
Organization:
Study Overview
Official Title:
Investigation of Plastic Changes in the CNS Associated With Peripheral Neuropathy
Status:
UNKNOWN
Status Verified Date:
2019-01
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: