Ignite Creation Date:
2024-05-06 @ 12:55 PM
Last Modification Date:
2024-10-26 @ 1:06 PM
Study NCT ID:
NCT03889080
Status:
UNKNOWN
Last Update Posted:
2022-07-26
First Post:
2018-11-21
Brief Title:
fMRI-study in Patients With Small Fiber Neuropathy
Sponsor:
Academisch Ziekenhuis Maastricht
Organization:
Academisch Ziekenhuis Maastricht
Study Overview
Official Title:
Central Pain Location in SCN9A-associated SFN an fMRI Pilot Study
Status:
UNKNOWN
Status Verified Date:
2022-07
Last Known Status:
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:
Small fiber neuropathy SFN is a form of peripheral neuropathy which is characterized by neuropathic pain and autonomic dysfunction Mutations in SCN9A the gene encoding for the voltage-gated sodium channel NaV17 are associated with SFN SCN9A-associated SFN often results in chronic neuropathic pain which is difficult to treat Chronic neuropathic pain may cause structural and functional changes in the brain Until now only one small study examined the structural and functional changes of the brain in SFN patients No studies have been performed in strictly defined SFN patients
Therefore it would be interesting to explore whether in SFN patients with an SCN9A mutation the genotype will lead to a distinct brain activation pattern on functional MRI fMRI and if the integrity or structural connectivity of the brain is altered using diffusion tensor imaging DTI This may provide a better understanding of the pathophysiological pathways for chronic pain and might serve as a biomarker for evaluating therapy
The objective of this study is to explore whether there is an indication whether patients with SCN9A-associated SFN have an abnormal brain activation pattern on resting state fMRI and during advanced thermal stimulation and altered structural connectivity on DTI versus SFN patients without a mutation and versus age- and gender-matched healthy controls With this knowledge objective pain measurement for patients with SFN may serve as a biomarker in evaluating efficacy of targeted therapy
Therefore it would be interesting to explore whether in SFN patients with an SCN9A mutation the genotype will lead to a distinct brain activation pattern on functional MRI fMRI and if the integrity or structural connectivity of the brain is altered using diffusion tensor imaging DTI This may provide a better understanding of the pathophysiological pathways for chronic pain and might serve as a biomarker for evaluating therapy
The objective of this study is to explore whether there is an indication whether patients with SCN9A-associated SFN have an abnormal brain activation pattern on resting state fMRI and during advanced thermal stimulation and altered structural connectivity on DTI versus SFN patients without a mutation and versus age- and gender-matched healthy controls With this knowledge objective pain measurement for patients with SFN may serve as a biomarker in evaluating efficacy of targeted therapy
Detailed Description:
Small fiber neuropathy SFN is a form of peripheral neuropathy which is characterized by neuropathic pain and autonomic dysfunction It is caused by dysfunction of the Aδ-fibers and C-fibers SFN is diagnosed if typical SFN symptoms are present in combination with an additional abnormal skin biopsy andor abnormal quantitative sensory testing The minimal prevalence of SFN is estimated to be 53100000 SFN has a comprehensive list of causes The etiology encompasses metabolic toxic auto immune infectious and hereditable causes Mutations in SCN9A the gene encoding for the voltage-gated sodium channel NaV17 are associated with SFN and can be found in 10-15 of SFN patients The symptomatic treatment of SFN is generally disappointing Until now antidepressants and anticonvulsants are mostly recommended for SFN with limited pain reduction often leading to chronic daily pain experience Understanding the pathophysiology of pain and identifying plausible specific pain genotype-phenotype relations might lead to improved treatment strategies Therefore the focus should extend beyond the scope of peripheral mechanisms of the nervous system and should include searching for pain complex central thus brain based mechanisms and patterns a pain network of somatosensory limbic and associate structures
The International Association for the Study of Pain defined pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage A painful stimulus activates the peripheral nociceptors and is transmitted through the small fibers via the dorsal horn in the spinal cord to the brain Pain stimuli are processed in the cortex subcortical structures and the midbrain In the cortical area the somatosensory anterior cingulate prefrontal and insular cortex are the most important structures whereas important subcortical areas encompass the hippocampus basal ganglia amygdala and thalamus Furthermore the cerebellum is suggested as an important area contributing to pain sensation
Chronic pain may lead to structural changes in the brain and imaging revealed morphological alterations in gray matter both an increase and a decrease The pattern of alterations may differ among different pain syndromes and may be reversible
Functional imaging studies have displayed specific brain activity patterns in patients with different types of pain syndromes Recently also in a small SFN patients study functional connectivity changes using a 30 Tesla scanner were shown However whether a specific activation pattern can be seen depends on many factors such as type of brain imaging modality7 It is conceivable that a particular type of pain stimulus may enhance a specific pain brain pattern but also specific person factors for example gender and genetic factors may influence the pain activation network Psychological modulation as well as chronicity of pain may influence the activation network and should therefore be taken into account Furthermore the specific location of pain can display different kinds of patterns because of partially somatotopic organization such as described in the S1 cortex To date in human no functional imaging studies using a 70 Tesla fMRI-scan have been performed
Until now an objective tool to measure pain is lacking Most studies in pain syndromes including patients with SFN have been using a great variety of surrogate pain scales such as the Visual Analogue Pain Scale VAS the Pain Intensity Numerical Rating Scale the Brief Pain Inventory and the Neuropathic pain scale NPS Therefore an objective measure for pain would be a great advantage
In this study patients with a SCN9A-associated SFN will be analyzed to determine possible central nervous system pain network patterns The voltage-gated sodium channel NaV17 plays a central role in pain processing Research in rats revealed areas of the brain that express Nav17 channels These channels were restricted to the hypothalamicpreoptic area brain stem and the subfornical organ Our goal is to examine whether gain-of-function mutations in NaV17 may lead to a specific pain pattern in the human brain by scanning with a 30 Tesla fMRI-scan Some patients will be included to undergo an extra fMRI-brain scan Tesla 70 Due to the high field strength new opportunities have arisen for brain imaging The newly acquired ultra high resolution facilitates the possibility of more detailed anatomical imaging When the 70 Tesla fMRI-scan appears to yield more useful information than the 30 Tesla fMRI-scan the first-mentioned will be used for follow-up studies
The aim of this study is to determine the resting state and the effect on heat stimuli of patients with SCN9A-associated SFN on fMRI and the changes in structural connectivity using diffusion tensor imaging DTI This may provide a better understanding of the pathophysiological pathways for chronic pain If successful fMRIDTI might be an additional tool as biomarker for evaluating therapy and may contribute in the evaluation of novel therapeutic strategies
The International Association for the Study of Pain defined pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage A painful stimulus activates the peripheral nociceptors and is transmitted through the small fibers via the dorsal horn in the spinal cord to the brain Pain stimuli are processed in the cortex subcortical structures and the midbrain In the cortical area the somatosensory anterior cingulate prefrontal and insular cortex are the most important structures whereas important subcortical areas encompass the hippocampus basal ganglia amygdala and thalamus Furthermore the cerebellum is suggested as an important area contributing to pain sensation
Chronic pain may lead to structural changes in the brain and imaging revealed morphological alterations in gray matter both an increase and a decrease The pattern of alterations may differ among different pain syndromes and may be reversible
Functional imaging studies have displayed specific brain activity patterns in patients with different types of pain syndromes Recently also in a small SFN patients study functional connectivity changes using a 30 Tesla scanner were shown However whether a specific activation pattern can be seen depends on many factors such as type of brain imaging modality7 It is conceivable that a particular type of pain stimulus may enhance a specific pain brain pattern but also specific person factors for example gender and genetic factors may influence the pain activation network Psychological modulation as well as chronicity of pain may influence the activation network and should therefore be taken into account Furthermore the specific location of pain can display different kinds of patterns because of partially somatotopic organization such as described in the S1 cortex To date in human no functional imaging studies using a 70 Tesla fMRI-scan have been performed
Until now an objective tool to measure pain is lacking Most studies in pain syndromes including patients with SFN have been using a great variety of surrogate pain scales such as the Visual Analogue Pain Scale VAS the Pain Intensity Numerical Rating Scale the Brief Pain Inventory and the Neuropathic pain scale NPS Therefore an objective measure for pain would be a great advantage
In this study patients with a SCN9A-associated SFN will be analyzed to determine possible central nervous system pain network patterns The voltage-gated sodium channel NaV17 plays a central role in pain processing Research in rats revealed areas of the brain that express Nav17 channels These channels were restricted to the hypothalamicpreoptic area brain stem and the subfornical organ Our goal is to examine whether gain-of-function mutations in NaV17 may lead to a specific pain pattern in the human brain by scanning with a 30 Tesla fMRI-scan Some patients will be included to undergo an extra fMRI-brain scan Tesla 70 Due to the high field strength new opportunities have arisen for brain imaging The newly acquired ultra high resolution facilitates the possibility of more detailed anatomical imaging When the 70 Tesla fMRI-scan appears to yield more useful information than the 30 Tesla fMRI-scan the first-mentioned will be used for follow-up studies
The aim of this study is to determine the resting state and the effect on heat stimuli of patients with SCN9A-associated SFN on fMRI and the changes in structural connectivity using diffusion tensor imaging DTI This may provide a better understanding of the pathophysiological pathways for chronic pain If successful fMRIDTI might be an additional tool as biomarker for evaluating therapy and may contribute in the evaluation of novel therapeutic strategies
Study Oversight
Has Oversight DMC:
None
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?:
None