Magnetic Brain Stimulation in Small Fiber Neuropathy
ConditionSmall Fiber Neuropathy
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorMaastricht University Medical Center
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Transcranial Magnetic Stimulation
DeviceTranscranial 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 Sham
DeviceA placebo version of the active repetitive transcranial magnetic stimulation. The coil mimics sound and sensation of a real treatment without active stimulation.
Treatment groups
124 Participants
are divided into 4 treatment groupsGroup A: Active rTMS- induction phaseExperimental treatment 1 intervention
Group B: Sham rTMS- induction phaseSham comparator 1 intervention
Group C: Active rTMS- maintenance phaseExperimental treatment 1 intervention
Group D: Sham rTMS- maintenance phaseSham comparator 1 intervention
Trial outcomes
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.
Time frame
From enrolment until 6 weeks of active rTMS treatmentSecondary outcomes
1
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 treatment2
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 123
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 64
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 monthsOther outcomes
1
Concomitant medication
Concomitant medication will be registered.
Time frame
From enrolment until month 6Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Maastricht University Medical Center
Lead sponsor
Princess Beatrix Muscle Foundation
Collaborator
Source ClinicalTrials.gov