fMRI-study in Patients With Small Fiber Neuropathy

NCT03889080 | Unknown

• 1 other identifier: fMRI-SFN
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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 NaV1.7, 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.

Conditions

Small Fiber Neuropathy

Keywords

functional MRI; fMRI; pain

Outcome Measures

Primary Outcomes (2)

• BOLD during heat stimulation

  BOLD (blood-oxygen-level dependent) signal in 3 study cohorts (individuals with SCN9A mutation with small fiber neuropathy, individual with SCN9A mutation without small fiber neuropathy and matched, healthy controls) during heat stimulation. \[ Time Frame: 1 day, single timepoint\] Difference in BOLD signal measured by functional magnetic resonance imaging (fMRI) between study cohorts in primary somatosensory cortex, thalamus, dorsal striatum and ventral striatum.

  Once (1 day)

• BOLD during cold stimulations

  BOLD (blood-oxygen-level dependent) signal in 3 study cohorts (individuals with SCN9A mutation with small fiber neuropathy, individual with SCN9A mutation without small fiber neuropathy and matched, healthy controls) during cold stimulation. \[ Time Frame: 1 day, single timepoint\] Difference in BOLD signal measured by functional magnetic resonance imaging (fMRI) between study cohorts in primary somatosensory cortex, thalamus, dorsal striatum, and ventral striatum.

  Once (1 day)

Secondary Outcomes (2)

• Resting state

  Once (1 day)

• Fractional anisotropy

  Once (1 day)

Study Arms (3)

SCN9A-group

Patients with SCN9A-associated small fiber neuropathy

Diagnostic Test: functional MRI

Skin biopsy

Patients with SFN confirmed with a decreased intra-epidermal nerve fiber density (IENFD)

Diagnostic Test: functional MRI

Control

Age- and gender-matched healthy controls

Diagnostic Test: functional MRI

Interventions

functional MRI DIAGNOSTIC_TEST

functional MRI scan of the brain

Control; SCN9A-group; Skin biopsy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients can only participate when they are living in the Netherlands.

You may qualify if:

• Patient group (SCN9A-associated SFN)
• Male and/or female subjects between the ages of 18 and 80 years.
• Presence of a clinical diagnosis of SFN, according to international criteria, and presence of confirmed abnormality on intra-epidermal nerve fiber density evaluation (IENFD) and/or Quantitative Sensory Testing (QST).
• A mutation in the SCN9A gene, confirmed by sequencing, with possible, probable or certain pathogenicity according to international criteria.
• Presence of pain due to SFN for at least 3 months and an average self-reported pain score of at least 5.
• Subjects must give informed consent by signing and dating an informed consent form.
• Patient group (SFN without a gene mutation):
• Male and/or female subjects between the ages of 18 and 80 years.
• Presence of a clinical diagnosis of SFN, according to international criteria, including a decreased intra-epidermal nerve fiber density IENFD in skin biopsy.
• No mutation in the SCN9A, SCN10A or SCN11A gene, confirmed by sequencing.
• Presence of pain due to SFN for at least 3 months and an average self-reported pain score of at least 5.
• Subjects must give informed consent by signing and dating an informed consent form.
• Control group
• Male and/or female subjects between the ages of 18 and 80 years.
• Subjects must give informed consent by signing and dating an informed consent form

You may not qualify if:

• For all groups:
• Major depression according to DSM-V criteria or a history of major psychiatric disease.
• (History of) alcohol abuse
• HADS ≥ 14
• Subjects who have another pain syndrome than small fiber neuropathy.
• Contraindications for undergoing MRI: pacemaker, metallic foreign body (including aneurysm clip in the brain), claustrophobia, pregnancy, neurostimulator, pacemaker or other kinds of implanted devices or insulin pump. In case of cardiac valve replacement of ossicular replacement prosthesis the radiologist will be consulted.

Sponsors & Collaborators

• Academisch Ziekenhuis Maastricht: lead
• Harvard University: collaborator

Study Sites (1)

Maastricht University Medical Center

Maastricht, Netherlands

RECRUITING

Related Publications (1)

• van Gool R, Far A, Drenthen GS, Jansen JFA, Goijen CP, Backes WH, Linden DEJ, Merkies ISJ, Faber CG, Upadhyay J, Hoeijmakers JGJ. Peripheral Pain Captured Centrally: Altered Brain Morphology on MRI in Small Fiber Neuropathy Patients With and Without an SCN9A Gene Variant. J Pain. 2024 Mar;25(3):730-741. doi: 10.1016/j.jpain.2023.10.002. Epub 2023 Nov 3.

  PMID: 37921732 DERIVED

MeSH Terms

Conditions

Small Fiber Neuropathy; Pain

Interventions

Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. C.G. Faber

Study Record Dates

• First Submitted: November 21, 2018
• First Posted: March 26, 2019
• Study Start: October 5, 2018
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: July 26, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)