Transcranial Magnetic Stimulation for Pain Management in Small Fiber Neuropathy
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
We 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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,
研究组 & 干预措施
Active rTMS- induction phase
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.
干预措施: Transcranial Magnetic Stimulation (Device)
Sham rTMS- induction phase
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.
干预措施: Transcranial Magnetic Stimulation Sham (Device)
Active rTMS- maintenance phase
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).
干预措施: Transcranial Magnetic Stimulation (Device)
Sham rTMS- maintenance phase
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).
干预措施: Transcranial Magnetic Stimulation Sham (Device)
结局指标
主要结局
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.
时间窗: 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.
次要结局
- SFN related symptoms on the SFN-SIQ(From enrolment until month 6)
- Activity and participation level using SFN-RODS(From enrolment until month 6)
- Quality of Life using EuroQoL 5D(From enrolment until month 6)
- Adverse events(From enrolment up until 12 weeks and 6 months)
- 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)