An interventional study of Transcranial Magnetic Stimulation and Transcranial Magnetic Stimulation Sham in Small Fiber Neuropathy, sponsored by Maastricht University Medical Center. Recruiting at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-21.
Sponsored by Maastricht University Medical Center · Not applicable, Interventional, and Treatment
Small fiber neuropathy (SFN) is a condition in which the smallest nerve fibers are damaged. This leads to severe pain and disturbances in the body's automatic functions. As a result, quality of life is often substantially reduced.
Pain is one of the main symptoms of small fiber neuropathy. Unfortunately, the effects of currently available pain medications are often disappointing and may be accompanied by unacceptable side effects. Although the smallest nerve fibers do not function properly in SFN, the brain also appears to play a role in the symptoms. Specialized brain imaging studies have shown that brain activity and certain neural connections differ between patients with SFN and healthy individuals. Therefore, the brain may also represent a suitable target for treatment.
In several chronic pain conditions, it has been demonstrated that stimulation of specific brain regions using magnetic pulses delivered through a specialized coil can reduce pain. This treatment can be administered using repetitive Transcranial Magnetic Stimulation (rTMS), a safe and non-invasive technique that is already available in the Netherlands for people with severe depression. The effectiveness of rTMS has never been investigated in patients with small fiber neuropathy. In addition, the pain-relieving effects of treatment are often temporary. Maintenance treatment may offer a potential solution to this problem.
Small fiber neuropathy (SFN) is a peripheral neuropathy dominated by invalidating neuropathic pain, leading to a substantial decline of quality of life (QOL). Pharmacological treatment is often ineffective and causes debilitating side effects. Interestingly, while constituting a peripheral nerve condition, SFN is also characterized by changes in brain network connectivity as demonstrated by structural and functional brain imaging, making the brain a promising treatment target for SFN. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has been proven to be effective in chronic neuropathic pain treatment, by inducing changes in cortical excitability. However, the number of neuropathy patients that has been studied is limited, and induced analgesic effects were rather short-lived in duration.
The investigators hypothesize that rTMS is an effective treatment strategy for neuropathic pain in SFN compared to sham stimulation. The primary objective is to evaluate the efficacy of rTMS for pain alleviation in SFN patients. Secondary objectives are to assess the effect of providing repeated maintenance rTMS treatment on prolonged pain relief, and to study the effect of rTMS on pain intensity, pain qualities, other SFN-related complaints, daily functioning and QoL, as well as safety features of rTMS in SFN.
50 studies on the registry are indexed under Small Fiber Neuropathy; 12 are open to participants now.
This study's planned enrollment of 124 is above the median of 31 across 31 interventional studies indexed under Small Fiber Neuropathy.
Browse Small Fiber Neuropathy studies →Maastricht University Medical Center is the lead sponsor of 853 studies on the registry; 114 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
During the first six weeks an active rTMS is given with 14 sessions in total. During the first two weeks 4 sessions a week, followed by two weeks of 2 sessions per week and two weeks of 1 session per week.
Device: Transcranial Magnetic Stimulation
During the first six weeks a sham rTMS is given with 14 sessions in total. During the first two weeks 4 sessions a week, followed by two weeks of 2 sessions per week and two weeks of 1 session per week.
Device: Transcranial Magnetic Stimulation Sham
If participants in the active group are responders (\>1 point difference on the PI-NRS compared to baseline) after 6 weeks, they will be randomised again for six weeks maintenance (1 session per week; 6 sessions total).
Device: Transcranial Magnetic Stimulation
If participants in the active group are responders (\>1 point difference on the PI-NRS compared to baseline) after 6 weeks, they will be randomised again for six weeks maintenance (1 session per week; 6 sessions total).
Device: Transcranial Magnetic Stimulation Sham
Transcranial magnetic stimulation (TMS) is arguably the most versatile noninvasive neuromodulation technique. TMS is the transcranial delivery of magnetic pulses to a brain region, inducing electric current that can depolarize neurons and induce action potentials. When multiple electromagnetic pulses are applied repetitively (rTMS) to the brain, longer lasting neuroplastic changes can be induced
A placebo version of the active repetitive transcranial magnetic stimulation. The coil mimics sound and sensation of a real treatment without active stimulation.
Proportion of responders, defined as ≥ 1-point improvement in the mean weekly peak pain measured with the PI-NRS after the 6-week treatment period.
As pain is the main future of SFN, the primary outcome measure will be based on pain intensity. This will be evaluated using the 11-point PI-NRS (0 = no pain to 10 = worst imaginable pain). The primary outcome parameter is defined as the difference in the mean weakly peak pain intensity. A responder is defined as ≥ 1-point decline on the PI-NRS at week 6 compared to baseline. The primary outcome measure is based on the IMMPACT criteria.12 The primary efficacy endpoint is the proportion of responders of rTMS compared to the proportion of responders of sham stimulation after the 6-week treatment period.
Time frame: From enrolment until 6 weeks of active rTMS treatment
Proportion of responders defined as ≥ 2-point decline on the PI-NRS at week 6 compared to baseline.
A secondary efficacy endpoint is a comparison between the percentage responders treated by rTMS and sham stimulation, when the responder is defined as ≥ 2-point decline on the PI-NRS at week 6 compared to baseline.
Time frame: From enrolment until 6 weeks of treatment
Efficacy of maintenance treatment based on pain intensity.
Also, the efficacy of the maintenance treatment is based on pain intensity. The maintenance period is successful, if the PI-NRS at week 12 is still ≥ 1-point lower compared to baseline.
Time frame: From enrolment until week 12
Changes in daily pain intensity using the PI-NRS
The daily pain intensity (defined as the mean pain experienced during the day: from waking up to 6 pm), the nocturnal pain intensity (6 pm until waking up), and the average of these two, using the PI-NRS.
Time frame: From enrolment until month 6
Pain changes on the Patient Global Impression of Change (PGIC)
Pain symptoms, using the patients' global impression of change (PGIC) on a 7-point Likert scale. Subsequent scores of the PGIC are 1) worse than ever; 2) much worse; 3) little worse; 4) no change; 5) little improved; 6) much improved; 7) very much improved. 'Very much improved and 'much improved' are considered as a relevant improvement. Clinically relevant pain reduction on PGIC for pain will be defined as score 6 ('much improved') or 7 ('very much improved').
Time frame: From enrolment until 6 months
Severity of various pain qualities, using the neuropathic pain scale (NPS).
Severity of various pain qualities, using the neuropathic pain scale (NPS). Scores are based on patient responses to questions about pain intensity. 0 indicates no pain; 10 indicates the most pain imaginable and the scale exists of 10 items.
Time frame: From enrolment until 6 months
SFN related symptoms on the SFN-SIQ (Small fiber neuropathy- symptom inventory questionairre)
SFN-related symptoms, measured by the Rasch-transformed 13 items SFN symptoms inventory questionnaire (RT-SFN-SIQ). The questions exist of small fiber neuropathy symptoms and how frequently they occur to the patient (never; sometimes; often; always) . The raw score ranges from 0 to 39 and is converted to a centile metric ranging from 0 to 100.
Time frame: From enrolment until month 6
Activity and participation level using SFN-RODS (Small Fiber Neuropathy- Rasch-built Overall disability Outcome Scale)
Activity and participation level, measured by the Rasch-built Overall disability Outcome Scale specifically designed for SFN (SFN-RODS). It consists of 32 items and focuses on daily activities and if a patient is able to carry that out (not able to carry out; with difficulty able to carry out; easily able to carry out). The raw score ranges from 0 to 64 and is converted to a centile metric ranging from 0 to 100.
Time frame: From enrolment until month 6
Quality of Life using EuroQoL 5D-5L
Quality of Life, using EQ5D (EuroQol 5D). The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
Time frame: From enrolment until month 6
Adverse events
Adverse events and vital signs will be registered for safety evaluation
Time frame: From enrolment up until 12 weeks and 6 months
Concomitant medication
Concomitant medication will be registered.
Time frame: From enrolment until month 6
Plan to share: Undecided
Start is estimated for Sep 2026; primary completion for Sep 2028, 24 months later.
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