Long Term, Double Blind, Randomized, Placebo Controlled Multi-center Study of FRE.M.S.- Frequency Modulated Neural Stimulation Lorenz Therapy™ in Symptomatic Diabetic Neuropathy
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 164
- 试验地点
- 11
- 主要终点
- Change in Nerve Conduction Velocity of the Deep Peroneal, Tibial, or Sural Nerve
研究概览
简要总结
Aim of this study is to evaluate safety and efficacy of transcutaneous frequency modulated electromagnetic neural stimulation (FREMS) to treat symptomatic peripheral neuropathy in patients with diabetes mellitus.
详细描述
Diabetic neuropathy is a common and potentially disabling complication of patients with type 1 or type 2 diabetes due to the damage of peripheral nerves caused by chronic hyperglycemia. The most common clinical signs and symptoms of diabetic neuropathy include numbness, diminished sensation and painful symptoms, such as burning, pins and needles, intolerable pain and hyperaesthesia of the lower extremities.
Different classes of drugs, such as analgesics, antidepressants and anti-epileptics are variably efficacious in pain relief, but are unfortunately unable to revert the natural history of the disease.
A wide range of electrotherapies have been proposed for the non-pharmacological treatment of diabetic neuropathy. The rationale of using electric or magnetic stimulation is the potential enhancement of microcirculation and endoneural blood flow, possibly counteracting the nerve ischemic damage, together with other yet poorly understood mechanisms, such as masking pain by interfering with pain gate control.
A number of studies have reported the efficacy of different electrotherapies, such as transcutaneous electrical nerve stimulation (TENS), pulsed-dose electrical stimulation, peripheral nerve, nerve root, spinal cord, deep brain and epidural motor cortex stimulations, pulsed (electro-)magnetic fields and static magnetic fields, high-frequency external muscle stimulation, high-tone external muscle stimulation and external muscle stimulation. However, of all these electrotherapies, only TENS is currently recommended as a treatment for painful diabetic neuropathy by the American Academy of Neurology.
Recently, a novel transcutaneous frequency-modulated electromagnetic neural stimulation (also named as Frequency Rhythmic Electrical Modulation System, FREMS), has been developed. FREMS consists of a sequence of modulated electrical stimuli that varies automatically in terms of pulse frequency, duration and voltage amplitude. FREMS was tested in a pilot randomized, cross-over study, and reduced diabetic neuropathy pain and ameliorated the sensory tactile and vibration perception threshold and motor nerve conduction velocity compared to a sham treatment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 1 or Type 2 diabetes
- •Diabetes duration of > 1 year
- •Age: 18 to 75 years
- •Symptomatic neuropathy
- •Abnormal amplitude, latency or conduction velocity in at least one motor nerve (Tibial or Peroneal) or in the Sural Nerve
- •A measurable Sural Nerve conduction velocity
- •Stable glycemic control in the last 3 months, HbA1C < 11%
- •MDNS score > 7
- •Stable dose of analgesic medications, if any, in the month prior enrollment
排除标准
- •Previous treatment with TENS or other electrotherapy
- •Motor or Sensitive nerve conduction velocity < 30 non recordable/evocable
- •Unstable glycemic control during last 3 months
- •Pregnancy
- •Implanted pacemaker or defibrillator or neurostimulator
- •Cancer diagnosed in the last 5 years
- •Psychological or psychiatric disorders that in the Investigator's opinion may interfere with patient's compliance to study procedures
- •Active foot ulcer and/or major lower limb amputation
- •Diabetic mononeuropathy
- •Severe peripheral artery disease (Leriche Fontaine scale grade 3 and 4)
- •Ankle-brachial index (ABI) < 0.7
- •Uremic neuropathy or end-stage renal disease
- •Toxic neuropathies
- •Severe hepatic disease
- •Alcohol consumption ≥ 40 g/day or 30 units/week
结局指标
主要结局
Change in Nerve Conduction Velocity of the Deep Peroneal, Tibial, or Sural Nerve
时间窗: baseline and 51 weeks
Change in Nerve Conduction Velocity of the Deep Peroneal , Tibial, or Sural Nerve at 51 weeks (i.e., after three cycles of FREMS treatment) versus baseline
次要结局
- Change in Vibration Perception Threshold(baseline and 51 weeks)
- Change in Cold Sensory Threshold(baseline and 51 weeks)
- Change in Warm Sensory Threshold(baseline and 51 weeks)
- Change in Day Pain Intensity (Visual Analogue Scale)(week 34 and week 37)
- Change in Night Pain Intensity (Visual Analogue Scale)(week 34 and week 37)
- Change in the Michigan Diabetic Neuropathy Score (MDNS)(baseline and 51 weeks)
- Change in the dose and type of analgesic medications(baseline and 51 weeks)
- Number of patients with treatment-related adverse events(baseline and 51 weeks)