Investigation of Plastic Changes in the CNS Associated With Peripheral Neuropathy

NCT03805893 | Unknown

• 1 other identifier: 1811001903
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Peripheral Neuropathy

Outcome Measures

Primary Outcomes (3)

• 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.

  Day 0

• 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.

  Day 0

• Pain Scale Assessment

  Neuropathy Pain Scale (NPS) instrument. Units is a score between 0 (no pain) and 100 (worst possible pain).

  Day 0

Interventions

Moderate heat pain PROCEDURE

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.

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Wayne State University: lead

MeSH Terms

Conditions

Peripheral Nervous System Diseases

Condition Hierarchy (Ancestors)

Neuromuscular Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: Two groups: patients with peripheral neuropathy and normal controls

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 16, 2019
• Study Start: February 1, 2019
• Primary Completion: November 30, 2020
• Study Completion: December 31, 2020
• Last Updated: January 16, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share