A Double-Blind, Randomized, Sham-Controlled, Crossover Study on the Efficacy of Burst Spinal Cord Stimulation in Patients With Severe Refractory Primary or Secondary RLS: the REST-SCS Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- RLS symptom severity
研究概览
简要总结
A Double-Blind Randomized Controlled Crossover Study to compare the short-efficacy of Burst-SCS with Sham Stimulation, in patients with severe to very severe RLS refractory or intolerant to standard available treatments and/or patients in augmentation, with a two-period-alternating treatment design.
详细描述
Restless Legs Syndrome (RLS) is a common chronic sleep disorder characterized by an irresistible urge to move the legs, often accompanied by unpleasant sensations that worsens during rest, particularly at night, and improves with movement. Affecting around 5% of the population, moderate to severe RLS can lead to insomnia, involuntary leg movements during sleep (PLMS), depression, and increased cardiovascular risk, significantly impacting sleep and quality of life and typically requiring long-term treatment.
While the exact cause of RLS is unknown, genetic factors, dopamine system alterations, iron deficiency in the brain, and opioid pathways are suspected contributors. It's mainly classified as primary (unknown cause), with secondary RLS linked to other conditions.
Current first-line treatments involve dopamine agonists (DAs) and alpha-2-delta ligands, which are generally effective but can have long-term limitations. A major issue with DAs is "augmentation," a worsening of RLS symptoms that often leads to treatment discontinuation. DAs are also less effective for insomnia, often requiring combination with sedatives. Opioids are effective but are second-line due to side effects and addiction risk. Importantly, while DAs help with sensory symptoms, they often don't significantly improve sleep quality.
Emerging as a promising non-pharmacological approach is electrical neuromodulation, particularly spinal cord stimulation (SCS). Case studies have shown that SCS can improve RLS symptoms, reduce PLMS, and enhance sleep quality, although long-term efficacy has been variable. The potential mechanism of SCS involves activating sensory fibers and inhibitory interneurons in the spinal cord, influencing pain pathways, and modulating brain regions involved in motor control and sleep regulation. This multilevel action may explain the potential benefits of SCS across the sensory, sleep, and motor aspects of RLS.
SCS, typically used for chronic intractable pain, is being investigated as a potential treatment for severe RLS due to overlapping characteristics between the two conditions. RLS has a sensory component that can include pain, and there's evidence suggesting a link between RLS and chronic pain based on high comorbidity, similar sensory processing abnormalities, the effectiveness of certain medications (opioids and α2δ ligands), and a shared hyperexcitable state in the central nervous system. Notably, some patients receiving SCS for chronic pain have also experienced improvement in their RLS symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female (all sexes) aged 18 years or older, inclusive;
- •Diagnosis of primary or secondary RLS;
- •Severe to very severe RLS defined as IRLS-RS score > 20;
- •Duration of RSL symptoms ≥ 6 months;
- •Insufficient symptom control achieved by and/or intolerance to established mono- or combination therapy of standard pharmacological treatment incl. patients in augmentation;
- •Stable pharmacologic therapy for RLS for at least 1 month;
- •A stable pattern of neurological symptoms;
- •Patients who are legally competent and able to understand the nature, scope and aim of the clinical trial;
- •Signed informed subject consent form
排除标准
- •Known hypersensitivity or allergy to the materials of the device;
- •Concomitant use of psychoactive-drugs (e.g. benzodiazepines, antidepressants; wash-out period: at least 7 days or longer depending on half-life);
- •Co-morbid sleep disorders influencing sleep structure and nocturnal motor pattern (e.g. Narcolepsy, REM sleep behaviour disorder etc.);
- •Coagulopathy or oral anticoagulant therapy (except low-dose acetylsalicylic acid) in conditions that do not allow for a temporary discontinuation;
- •Active infection, systemic or localized;
- •Known immune deficiency;
- •Presence of spinal cord or peripheral nerve stimulators;
- •Any disease process or condition that may make the effect of the treatment difficult to evaluate (e.g. cancer with low life expectancy);
- •Severe psychiatric disorders (including substance abuse, major depression, and similar severe disorders known or suspected non-compliance) which could have a negative influence on successful treatment;
- •Inability to follow the procedures of the study, e.g. due to language problems, dementia, etc. of the participant;
- •Women who are pregnant or breast feeding;
- •Intention to become pregnant during the course of the study;
研究组 & 干预措施
Treatment phase: Sham-stimulation
After IPG implantation Burst-SCS is turned on in all participants for 2.5. Then, they will again be double-blind randomized to the 2 treatment orders for 2 weeks per stimulation mode (Sham stimulation or SCS) as fcollows:
- Double-blind randomization to the following alternating treatment modes:
- 14 days Sham-stimulation + 14 days SCS
- 14 days SCS + 14r days Sham-stimulation
干预措施: Sham stimulation (Device)
Treatment phase: SCS-stimulation
After IPG implantation Burst-SCS is turned on in all participants for 2.5. Then, they will again be double-blind randomized to the 2 treatment orders for 2 weeks per stimulation mode (Sham stimulation or SCS) as fcollows:
- Double-blind randomization to the following alternating treatment modes:
- 14 days Sham-stimulation + 14 days SCS
- 14 days SCS + 14r days Sham-stimulation
干预措施: Spinal cord stimulation (SCS) (Device)
结局指标
主要结局
RLS symptom severity
时间窗: From baseline of the treatment phase to the end of the 2.5 months treatment phase
Change in RLS symptoms and severity as measured by the International RLS-Rating-scale (IRLS-RS) score. The IRLS-RS is a self-administered 10-item questionnaire to assess the severity of sleep disruption and symptoms in RLS patients. It has been validated by the International RLS Study group. Each item is scored from 4 (very severe) to 0 (none). The final score ranges between 0 and 40 and classifies RLS as mild (1-10), moderate (11-20), severe (21-30) and very severe (31-40). A negative change will indicate an improvement in IRLS-RS score and, therefore, in the severity of sleep disruption and symptoms of RLS.
次要结局
- Treatment response to SCS in %(From baseline of the treatment phase to end of the 2.5 months treatment phase)
- Change in general health quality of life(From baseline of the treatment period to the end of the 2.5 months treatment phase)
- Change in RLS-related quality of life(From baseline of the treatment period to the end of the 2.5 months treatment phase)
- Change of Total Sleep Time (TST), Sleep Latency (SL) and Sleep Efficacy (SE) acquired by actigraphy(From baseline of the treatment period to the end of the 1 month SCS stimulation during the cross-over of the treatment period)
- Change of PLMS Index recorded by PSG(From baseline of the treatment period to the end of the 1 month SCS stimulation during the cross-over of the treatment period)
- Difference in RLS symptoms and severity between 1 month of SCS vs. Sham stimulation(Between 1 month of SCS vs. Sham stimulation)
- Difference in health-related quality of life between 1 month of SCS vs. Sham stimulation(Between 1 month of SCS vs. Sham stimulation)
- Difference in RLS-related quality of life between 1 month of SCS vs. Sham stimulation(Between 1 month of SCS vs. Sham stimulation)
- Difference between 1 month of SCS vs. Sham stimulation in TST, SL and SE(Between 1 month of SCS vs. Sham stimulation)
- Change of sleep parameters recorded by PSG(From baselene of the treatment period to the end of the 1 month SCS stimulation during the cross-over of the treatment period.)
- Difference between one month of SCS vs. Sham stimulation in PLMS index, TST, SL, SE, number of awakenings and arousal index(Between 1 month of SCS vs. Sham stimulation)
研究者
Eva Koetsier
Clinical Professor Eva Koetsier, PhD, LL.M, Specialist in Anaesthesiology and Interventional Pain Management
Clinica ARS Medica