To explore whether patients with SCN9A-associated SFN have an abnormal brain activation pattern on resting state fMRI and altered structural connectivity on DTI versus age- and gender-matched healthy controls. With this knowledge, objective pain…
ID
Source
Brief title
Condition
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Concerning the fMRI, change of connectivity in the central executive network
(CEN) and sensorimotor network (SMN) is the primary endpoint.
Change in brain connectivity have been observed in several neuropathic pain
conditions affecting mainly the networks mentioned above: SMN tend to show
hyperconnectivity while CEN hipoconnectivity. Concerning DTI, the study
parameters are fractional anisotropy (FA) and axial diffusivity (AD).
Secondary outcome
Not applicable
Background 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.
We hypothesize that SCN9A-associated SFN will lead to a specific brain
activation pattern on fMRI and altered structural connectivity on DTI.
Study objective
To explore whether patients with SCN9A-associated SFN have an abnormal brain
activation pattern on resting state fMRI and altered structural connectivity on
DTI 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.
Study design
This is a case-control study. It is a type of observational study in which
three existing groups differing in outcome are identified and compared.
Case-control studies are often used to identify factors that may contribute to
a medical condition by comparing subjects who have that condition/disease with
patients who do not have the condition/disease.
Three subjects from each group receive an additional MRI-scan (Tesla 7.0).
Study burden and risks
This pilot study provides a low burden for the participant. The participant
will visit our hospital only once. This visit lasts up to 90 minutes and will
consist of a anatomical MRI-scan, fMRI-scan and DTI-scan (max. 60 minutes) and
completing four questionnaires (remaining time). The contact time is estimated
for 120 minutes, including the intake and signing the informed consent forms.
Halfway the fMRI scan, a so-called advanced thermal stimulation (ATS) will be
performed with heat and cold stimulation. This can be unpleasant but is usually
not experienced as painful.
P. Debyelaan 25 -
Maastricht 6229 HX
NL
P. Debyelaan 25 -
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
Patient group (SCN9A-associated SFN) (n <= 20)
a. Male and/or female subjects between the ages of 18 and 80 years.
b. Presence of a clinical diagnosis of small fiber neuropathy, according to
international criteria and presence of confirmed abnormality on intra-epidermal
nerve fiber density evaluation and/or Quantitative Sensory Testing.
c. A mutation in the SCN9A gene, confirmed by sequencing, with possible,
probable or certain pathogenicity according to international criteria.
d. Presence of pain due to SFN for at least 3 months and an average
self-reported pain score of at least 5.
e. Subjects must give informed consent by signing and dating an informed
consent form., Patient group (SFN without a gene mutation)
a. Male and/or female subjects between the ages of 18 and 80 years.
b. Presence of a clinical diagnosis of SFN, according to international
criteria,1, 52, 53 including a decreased intra-epidermal nerve fiber density
IENFD in skin biopsy.
c. No mutation in the SCN9A, SCN10A or SCN11A gene, confirmed by sequencing.
d. Presence of pain due to SFN for at least 3 months and an average
self-reported pain score of at least 5.
e. Subjects must give informed consent by signing and dating an informed
consent form., Control group (n <= 20)
a. Male and/or female subjects between the ages of 18 and 80 years.
b. Subjects must give informed consent by signing and dating an informed
consent form.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
a. Major depression according to DSM-V criteria or a history of major
psychiatric disease.
b. (History with) alcohol abuse
c. Hospital Anxiety and Depression Scale (HADS) * 14
d. Subjects who have another pain syndrome than small fiber neuropathy.
e. 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.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL53441.068.15 |