Magnetic Brain Stimulation in Small Fiber Neuropathy

NCT07805057 | Recruiting DMC

• 2 other identifiers: NL-010948W.OR24-04
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Small Fiber Neuropathy

Keywords

repetitive transcranial magnetic stimulation; rTMS; small fiber neuropathy; SFN; pain management

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  From enrolment until 6 weeks of treatment

• Efficacy of maintenance treatment based on pain intensity.

  From enrolment until week 12

• Changes in daily pain intensity using the PI-NRS

  From enrolment until month 6

• Pain changes on the Patient Global Impression of Change (PGIC)

  From enrolment until 6 months

• Severity of various pain qualities, using the neuropathic pain scale (NPS).

  From enrolment until 6 months

Other Outcomes (1)

• Concomitant medication

  From enrolment until month 6

Study Arms (4)

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.

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.

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).

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).

Device: Transcranial Magnetic Stimulation Sham

Interventions

Transcranial Magnetic Stimulation DEVICE

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

Active rTMS- induction phase; Active rTMS- maintenance phase

Transcranial Magnetic Stimulation Sham DEVICE

A placebo version of the active repetitive transcranial magnetic stimulation. The coil mimics sound and sensation of a real treatment without active stimulation.

Sham rTMS- induction phase; Sham rTMS- maintenance phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Princess Beatrix Muscle Foundation: collaborator

Study Sites (1)

Maastricht University Medical Centre +

Maastricht, Limburg, 6229 HX, Netherlands

RECRUITING

Related Publications (25)

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MeSH Terms

Conditions

Small Fiber Neuropathy; Agnosia

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Janneke G.J. Hoeijmakers, MD, PhD

  Maastricht University Medical Centre +

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eva C.M. Gruintjes, MD

CONTACT

+31 433876584; eva.gruintjes@mumc.nl

Janneke G.J. Hoeijmakers, MD, PhD

CONTACT

+31 433877059; j.hoeijmakers@mumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized controlled trial, single blind.

Study Record Dates

• First Submitted: September 1, 2026
• First Posted: September 4, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: September 21, 2026

Record last verified: 2026-09

Locations

NL (1)