Small Fiber NeuropathyrTMS in SFNNCT07805057
Magnetic Brain Stimulation in Small Fiber Neuropathy
A study testing Transcranial Magnetic Stimulation in people with Small Fiber Neuropathy, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Fiber Neuropathy
- What is being tested?
- Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2026to Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older.
- Skin-biopsy proven idiopathic SFN.
- Pain intensity (maximum pain) rated ≥5 on the PI-NRS, that must have existed for at least 12 weeks before the study.
- Written informed consent.
Who cannot join
- Signs of large nerve fiber dysfunction (i.e., weakness, loss of vibration sense, hyporeflexia or areflexia, abnormal nerve conduction studies).
- Identifiable underlying cause of SFN (diabetes, SCN9A/SCN10A/SCN11A mutations, hypothyroidism, vitamin B12 deficiency, monoclonal gammopathy, alcohol abuse (more than 5 IU/day), malignancies, or drugs that cause neuropathy).
- Implanted ferromagnetic devices or other magnetic-sensitive metal implants close to the magnetic coil.
- History of epilepsy.
- Using pain medication that has changed in the 30 days prior to randomization.
- Pregnancy.
- Mentally challenged subjects unable to give independent informed consent.
- Clinically significant or unstable psychiatric disorder including major depression, (history of) substance abuse and other major disorders in accordance with DSM-V,
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Maastricht University Medical Centre +
Maastricht, Limburg, 6229 HX
Eva C.M. Gruintjes, MD, +31 433876584, eva.gruintjes@mumc.nl
Janneke G.J. Hoeijmakers, MD, PhD, +31 433877059, j.hoeijmakers@mumc.nl
About this study
Official title: Transcranial Magnetic Stimulation for Pain Management in Small Fiber Neuropathy
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.
Read the detailed description
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.
- Conditions
- Small Fiber Neuropathy
- Being tested
- Transcranial Magnetic Stimulation, Transcranial Magnetic Stimulation Sham
- Keywords
- repetitive transcranial magnetic stimulation, rTMS, small fiber neuropathy, SFN, pain management
- Medical subject headings
- Small Fiber Neuropathy, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
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
Transcranial Magnetic Stimulation ShamDevice
A placebo version of the active repetitive transcranial magnetic stimulation. The coil mimics sound and sensation of a real treatment without active stimulation.
| Study group | Role | What they receive |
|---|---|---|
| Active rTMS- induction phase | Experimental | 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. Receives: Device: Transcranial Magnetic Stimulation |
| Sham rTMS- induction phase | Sham comparator | 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. Receives: Device: Transcranial Magnetic Stimulation Sham |
| Active rTMS- maintenance phase | Experimental | 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). Receives: Device: Transcranial Magnetic Stimulation |
| Sham rTMS- maintenance phase | Sham comparator | 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). Receives: Device: Transcranial Magnetic Stimulation Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From enrolment until 6 weeks of active rTMS treatment
Secondary outcomes (9)
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.
Measured: 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.
Measured: 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.
Measured: 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').
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From enrolment until month 6
Adverse events
Adverse events and vital signs will be registered for safety evaluation
Measured: From enrolment up until 12 weeks and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2026
- Study startSep 2026 (estimated)
- Primary completionSep 2028 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Small Fiber NeuropathyStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled trial, single blind.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Princess Beatrix Muscle Foundation
- Responsible party
- Sponsor
- Investigators
- Janneke G.J. Hoeijmakers, MD, PhD, Principal investigator, Maastricht University Medical Centre +
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07805057
- Sponsor's protocol ID
- NL-010948
- Other IDs
- W.OR24-04
- Acronym
- rTMS in SFN
- Status last verified
- Sep 2026
- First submitted
- 1 Sep 2026
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 37921732Tsai YY, Wu WT, Han DS, Mezian K, Ricci V, Ozcakar L, Hsu PC, Chang KV. Application of Repetitive Transcranial Magnetic Stimulation in Neuropathic Pain: A Narrative Review. Life (Basel). 2023 Jan 17;13(2):258. doi: 10.3390/life13020258.
PubMed 36836613Tik M, Hoffmann A, Sladky R, Tomova L, Hummer A, Navarro de Lara L, Bukowski H, Pripfl J, Biswal B, Lamm C, Windischberger C. Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity. Neuroimage. 2017 Nov 15;162:289-296. doi: 10.1016/j.neuroimage.2017.09.022. Epub 2017 Sep 12.
PubMed 28912081Taylor JJ, Newberger NG, Stern AP, Phillips A, Feifel D, Betensky RA, Press DZ. Seizure risk with repetitive TMS: Survey results from over a half-million treatment sessions. Brain Stimul. 2021 Jul-Aug;14(4):965-973. doi: 10.1016/j.brs.2021.05.012. Epub 2021 Jun 13.
PubMed 34133991Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-1107. doi: 10.1016/j.clinph.2015.02.001. Epub 2015 Feb 10.
PubMed 25797650Robinson-Papp J, George MC, Dorfman D, Simpson DM. Barriers to Chronic Pain Measurement: A Qualitative Study of Patient Perspectives. Pain Med. 2015 Jul;16(7):1256-64. doi: 10.1111/pme.12717. Epub 2015 Feb 17.
PubMed 25688752Nurmikko T, MacIver K, Bresnahan R, Hird E, Nelson A, Sacco P. Motor Cortex Reorganization and Repetitive Transcranial Magnetic Stimulation for Pain-A Methodological Study. Neuromodulation. 2016 Oct;19(7):669-678. doi: 10.1111/ner.12444. Epub 2016 May 17.
PubMed 27187056Mori N, Hosomi K, Nishi A, Miyake A, Yamada T, Matsugi A, Jono Y, Lim C, Khoo HM, Tani N, Oshino S, Saitoh Y, Kishima H. Repetitive transcranial magnetic stimulation focusing on patients with neuropathic pain in the upper limb: a randomized sham-controlled parallel trial. Sci Rep. 2024 May 23;14(1):11811. doi: 10.1038/s41598-024-62018-x.
PubMed 38782994Molero-Chamizo A, Nitsche MA, Barroso RTA, Bailen JRA, Palomeque JCG, Rivera-Urbina GN. Non-Invasive Electric and Magnetic Brain Stimulation for the Treatment of Fibromyalgia. Biomedicines. 2023 Mar 20;11(3):954. doi: 10.3390/biomedicines11030954.
PubMed 36979932Leo RJ, Latif T. Repetitive transcranial magnetic stimulation (rTMS) in experimentally induced and chronic neuropathic pain: a review. J Pain. 2007 Jun;8(6):453-9. doi: 10.1016/j.jpain.2007.01.009. Epub 2007 Apr 16.
PubMed 17434804Lefaucheur JP, Nguyen JP. A practical algorithm for using rTMS to treat patients with chronic pain. Neurophysiol Clin. 2019 Sep;49(4):301-307. doi: 10.1016/j.neucli.2019.07.014. Epub 2019 Jul 30.
PubMed 31375381Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipovic SR, Grefkes C, Hasan A, Hummel FC, Jaaskelainen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorova I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol. 2020 Feb;131(2):474-528. doi: 10.1016/j.clinph.2019.11.002. Epub 2020 Jan 1.
PubMed 31901449Kool D, Hoeijmakers JG, Waxman SG, Faber CG. Small fiber neuropathy. Int Rev Neurobiol. 2024;179:181-231. doi: 10.1016/bs.irn.2024.10.001. Epub 2024 Oct 29.
PubMed 39580213Hsieh PC, Tseng MT, Chao CC, Lin YH, Tseng WI, Liu KH, Chiang MC, Hsieh ST. Imaging signatures of altered brain responses in small-fiber neuropathy: reduced functional connectivity of the limbic system after peripheral nerve degeneration. Pain. 2015 May;156(5):904-916. doi: 10.1097/j.pain.0000000000000128.
PubMed 25734991Hoeijmakers JG, Faber CG, Lauria G, Merkies IS, Waxman SG. Small-fibre neuropathies--advances in diagnosis, pathophysiology and management. Nat Rev Neurol. 2012 May 29;8(7):369-79. doi: 10.1038/nrneurol.2012.97.
PubMed 22641108
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Magnetic Stimulation for Pain Management in Small Fiber Neuropathy
- ClinicalTrials.gov ID
- NCT07805057
- Acronym / sponsor ID
- rTMS in SFN / NL-010948
- Conditions
- Small Fiber Neuropathy
- Keywords
- repetitive transcranial magnetic stimulation, rTMS, small fiber neuropathy, SFN, pain management
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 124 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Princess Beatrix Muscle Foundation
- Study start
- Sep 2026 (estimated)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2028 (estimated)
- First posted
- 4 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
- Model description
- Randomized controlled trial, single blind.
| Arm | Type | Receives |
|---|---|---|
| Active rTMS- induction phase | Experimental | Device: Transcranial Magnetic StimulationDuring 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. |
| Sham rTMS- induction phase | Sham comparator | Device: Transcranial Magnetic Stimulation ShamDuring 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. |
| Active rTMS- maintenance phase | Experimental | Device: Transcranial Magnetic StimulationIf 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). |
| Sham rTMS- maintenance phase | Sham comparator | Device: Transcranial Magnetic Stimulation ShamIf 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 18 years of age or older.
- Skin-biopsy proven idiopathic SFN.
- Pain intensity (maximum pain) rated ≥5 on the PI-NRS, that must have existed for at least 12 weeks before the study.
- Written informed consent.
Key exclusion criteria (8 listed)
- Signs of large nerve fiber dysfunction (i.e., weakness, loss of vibration sense, hyporeflexia or areflexia, abnormal nerve conduction studies).
- Identifiable underlying cause of SFN (diabetes, SCN9A/SCN10A/SCN11A mutations, hypothyroidism, vitamin B12 deficiency, monoclonal gammopathy, alcohol abuse (more than 5 IU/day), malignancies, or drugs that cause neuropathy).
- Implanted ferromagnetic devices or other magnetic-sensitive metal implants close to the magnetic coil.
- History of epilepsy.
- Using pain medication that has changed in the 30 days prior to randomization.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic StimulationTranscranial 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 | Device | Active rTMS- induction phase, Active rTMS- maintenance phase |
| Transcranial Magnetic Stimulation ShamA placebo version of the active repetitive transcranial magnetic stimulation. The coil mimics sound and sensation of a real treatment without active stimulation. | Device | Sham rTMS- induction phase, Sham rTMS- maintenance phase |
Primary outcome
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.
Time frame: From enrolment until 6 weeks of active rTMS treatment
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.
9 secondary outcomes
Proportion of responders 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.
Time frame: From enrolment until week 12
Changes in daily pain intensity using the PI-NRS
Time frame: From enrolment until month 6
Pain changes on the Patient Global Impression of Change (PGIC)
Time frame: From enrolment until 6 months
Severity of various pain qualities, using the neuropathic pain scale (NPS).
Time frame: From enrolment until 6 months
SFN related symptoms on the SFN-SIQ (Small fiber neuropathy- symptom inventory questionairre)
Time frame: From enrolment until month 6
Activity and participation level using SFN-RODS (Small Fiber Neuropathy- Rasch-built Overall disability Outcome Scale)
Time frame: From enrolment until month 6
Quality of Life using EuroQoL 5D-5L
Time frame: From enrolment until month 6
Adverse events
Time frame: From enrolment up until 12 weeks and 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Background: PubMed 37921732van 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.
- Background: PubMed 36836613Tsai YY, Wu WT, Han DS, Mezian K, Ricci V, Ozcakar L, Hsu PC, Chang KV. Application of Repetitive Transcranial Magnetic Stimulation in Neuropathic Pain: A Narrative Review. Life (Basel). 2023 Jan 17;13(2):258. doi: 10.3390/life13020258.
- Background: PubMed 28912081Tik M, Hoffmann A, Sladky R, Tomova L, Hummer A, Navarro de Lara L, Bukowski H, Pripfl J, Biswal B, Lamm C, Windischberger C. Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity. Neuroimage. 2017 Nov 15;162:289-296. doi: 10.1016/j.neuroimage.2017.09.022. Epub 2017 Sep 12.
- Background: PubMed 34133991Taylor JJ, Newberger NG, Stern AP, Phillips A, Feifel D, Betensky RA, Press DZ. Seizure risk with repetitive TMS: Survey results from over a half-million treatment sessions. Brain Stimul. 2021 Jul-Aug;14(4):965-973. doi: 10.1016/j.brs.2021.05.012. Epub 2021 Jun 13.
- Background: PubMed 25797650Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-1107. doi: 10.1016/j.clinph.2015.02.001. Epub 2015 Feb 10.
- Background: PubMed 25688752Robinson-Papp J, George MC, Dorfman D, Simpson DM. Barriers to Chronic Pain Measurement: A Qualitative Study of Patient Perspectives. Pain Med. 2015 Jul;16(7):1256-64. doi: 10.1111/pme.12717. Epub 2015 Feb 17.
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- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Janneke G.J. Hoeijmakers, MD, PhD principal investigator
Maastricht University Medical Centre +
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation in people with Small Fiber Neuropathy, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Eva C.M. Gruintjes, MD (+31 433876584, eva.gruintjes@mumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: From enrolment until 6 weeks of active rTMS treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07805057, which also lists 25 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.