Stanford University School of Medicine, Stanford, CA, USA.
Private Practice, Downey, CA, USA.
BMC Neurol. 2023 Nov 21;23(1):415. doi: 10.1186/s12883-023-03462-6.
There is a large population of restless legs syndrome (RLS) patients who are refractory to medication. Whereas experts recommend off-label opioids as an effective long-term treatment for refractory RLS, reducing opioid dose could substantially reduce side effects and risks. Tonic motor activation (TOMAC) is a nonpharmacological therapeutic device indicated for refractory RLS. Here, we investigated if TOMAC could enable opioid dose reduction for refractory RLS.
This prospective, open-label, single-arm clinical trial [NCT04698343] enrolled 20 adults taking ≤ 60 morphine milligram equivalents (MMEs) per day for refractory RLS. Participants self-administered 30-min TOMAC sessions bilaterally over the peroneal nerve when RLS symptoms presented. During TOMAC treatment, opioid dose was reduced iteratively every 2-3 weeks until Clinician Global Impression of Improvement (CGI-I) score relative to baseline exceeded 5. Primary endpoint was percent of participants who successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Secondary endpoints included mean successful percent opioid dose reduction with CGI-I ≤ 5.
On average, participants were refractory to 3.2 medications (SD 1.6) and were taking a stable dose of opioids for 5.3 years (SD 3.9). Seventy percent of participants (70%, 14 of 20) successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Mean percent opioid dose reduction with CGI-I ≤ 5 was 29.9% (SD 23.7%, n = 20) from 39.0 to 26.8 MME per day. Mean CGI-I score at the reduced dose was 4.0 (SD 1.4), indicating no change to RLS severity.
For refractory RLS, TOMAC enabled substantial opioid dose reduction without increased RLS symptoms. These results suggest that TOMAC has the potential to reduce the risk profile associated with opioid therapy for refractory RLS.
ClinicalTrials.gov trial number NCT04698343 registered on January 6, 2021.
有大量不宁腿综合征（RLS）患者对药物治疗无反应。虽然专家推荐将阿片类药物作为治疗难治性 RLS 的有效长期治疗方法，但降低阿片类药物剂量可以显著减少副作用和风险。经皮神经电刺激（TOMAC）是一种用于治疗难治性 RLS 的非药物治疗设备。在这里，我们研究了 TOMAC 是否可以降低难治性 RLS 的阿片类药物剂量。
这项前瞻性、开放标签、单臂临床试验（NCT04698343）纳入了 20 名每天服用≤60 吗啡毫克当量（MME）治疗难治性 RLS 的成年人。当 RLS 症状出现时，参与者自行双侧经皮神经电刺激腓总神经 30 分钟。在 TOMAC 治疗期间，每隔 2-3 周迭代降低阿片类药物剂量，直到相对于基线的临床医生总体印象改善（CGI-I）评分超过 5。主要终点是 CGI-I≤5 的参与者成功降低阿片类药物剂量≥20%的比例。次要终点包括 CGI-I≤5 的平均成功阿片类药物剂量降低百分比。
平均而言，参与者对 3.2 种药物（SD 1.6）无反应，且稳定服用阿片类药物 5.3 年（SD 3.9）。70%的参与者（70%，20 名中的 14 名）成功降低阿片类药物剂量≥20%，CGI-I≤5。CGI-I≤5 时的平均阿片类药物剂量降低百分比为 29.9%（SD 23.7%，n=20），从 39.0 降至 26.8 MME/天。减少剂量时的平均 CGI-I 评分为 4.0（SD 1.4），表明 RLS 严重程度无变化。
对于难治性 RLS，TOMAC 可显著降低阿片类药物剂量，而不会增加 RLS 症状。这些结果表明，TOMAC 有可能降低与难治性 RLS 阿片类药物治疗相关的风险。
ClinicalTrials.gov 试验编号 NCT04698343 于 2021 年 1 月 6 日注册。
