BotulInum Toxin Type A for Peripheral Neuropathic Pain in subjEcts With Carpal Tunnel Syndrome: a Multicenter, Randomized, Doubleblind, Placebo-controlled Study
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 164
- 试验地点
- 1
- 主要终点
- Efficacy of two successive administrations of several injections of BoNT-A, compared with placebo by NRS
研究概览
简要总结
The main purpose of the study is to assess the safety and efficacy of repeated administrations of BoNT-A in subjects with NP attributable to carpal tunnel syndrome (CTS) through a randomized, double-blind, placebo-controlled study. Further research has shown that BoNT-A has analgesic properties independently from its action on muscle tone, possibly by acting on neurogenic inflammation. Therefore, the study drug may be better than other treatments surgical or non-surgical currently available for the treatment of CTS.
详细描述
Botulinum toxin type A (BoNT-A) is widely used to treat muscle hyperactivity, based on its ability to inhibit synaptic exocytosis and, therefore, to disable neural transmission. Further research has shown that BoNT-A has analgesic properties independently from its action on muscle tone, possibly by acting on neurogenic inflammation. Animal studies indeed showed that botulinum neurotoxin can alter and alleviate NP in animals through several mechanisms, including blocking the release of pain mediators, decreasing local inflammation around nerve terminals, deactivating sodium channels, inhibiting the discharge of muscle spindles and decreasing sympathetic transmission.
Evidence on the use of BoNT-A in CTS and occipital neuralgia is still limited as it derives from small patient studies with controversial results, and is therefore considered still insufficient to determine whether or not BoNT-A could be part of the therapeutic arsenal against these NPs (level U). Overall, according to the litterature, the results of BoNT-A injections on NP are variable, as it seems to be effective in postherpetic neuralgia (evidence level A), may be effective in trigeminal neuralgia and post-traumatic neuralgia (level B) and is possibly effective in diabetic polyneuropathy (level C).
In this multicenter, randomized, double-blinding, placebo-controlled, parallel study it will enroll 164 subjects, both genders, aged ≥18 and ≤60 years old, to obtain 164 overall valuable subjects (23/24 for each center). The recruitment period (V1) will last 1 week after the baseline assessment, eligible subjects will be randomly assigned (1:1) to BoNT-A or placebo arm and will receive the first round of injections. After 12 week ±4 days (V2) subjects will undergo the second treatment round, receiving either a second BoNT-A administration or a second placebo administration. In week 24 ±4 days (V3) the same assessment scheduled for visit 1 will be repeated.
Benefit Assessment :
As described previously, BoNT-A showed some significant advantages over NPs existing treatments, such as the extended duration of its analgesic effects; BoNT-A has analgesic properties independently from its action on muscle tone, possibly by acting on neurogenic inflammation.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
To maintain the blinding of the study drug (BoNT-A or placebo), all study personnel will be blinded to subjects' treatment assignment. Physicians, nurses, subjects, and any study personnel performing assessments must NOT be informed of the subject's treatment assignment except in the event of a medical emergency or as required by regulatory authorities. The injection syringes will be prepared by pharmacy personnel not involved in the study to ensure that the clinical site staff responsible for administering the study drug and conducting assessments per the protocol, and the subject, remain blinded to study treatment. Moreover, the BoNT-A and placebo solution will be limpid and indistinguishable, to maintain blindness. Both subjects, investigators and study personnel will maintain blindness to the treatments throughout the study.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subject aged ≥18 and ≤60 years old.
- •Probable or definitive NP according to the International Association for the Study of Pain criteria.
- •Daily pain attributable to CTS for at least 6 months. This must be attributable to idiopathic carpal tunnel syndrome and with nerve conduction velocity findings consistent with this condition
- •Moderate-severe pain according to the 11-point Numerical. Rating Scale (NRS; 4-8)
- •We allow the concomitant use of analgesic treatments if they have been used at a stable doses for 4 weeks before the enrolment and for the whole study.
- •Signed informed consent prior to participation in the study
排除标准
- •Pain level ≥9 on 11-point NRS.
- •CTS with atrophy of median-innervated muscles and EMG study suggesting a severe nerve injury.
- •Subject with contraindications or hypersensitivity to BoNT-A.
- •Subject with disorders of the neuromuscular junction, progressive neuropathy disorders, coagulation disorders or major psychiatric disorders.
- •Subject with diabetes, rheumatoid arthritis, connective tissue diseases, vasculitis, untreated hypothyroidism, acromegaly.
- •Subject using drugs acting on neuromuscular junctions, topical drugs (e.g., capsaicin or lidocaine), or anesthetic blocks.
- •Subject has used BoNT-A.
- •Subject is pregnant or breastfeeding women.
- •Subject enrolled in another interventional trial for the treatment of of the same disease.
研究组 & 干预措施
Experimental group: BoNT-A arms
Subjects randomized in experimental group will receive intradermal injections of BoNT-A into the wrist and skin area of the hand where the pain is located.
干预措施: BoNT-A (Drug)
Control group: Placebo arms
Subjects randomized in control group will receive intradermal injections of placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Efficacy of two successive administrations of several injections of BoNT-A, compared with placebo by NRS
时间窗: 25 weeks
The primary outcome is mesured as: - Change in weekly self-reported maximum daily pain intensity (maximum pain intensity over the past 24 hours recorded every morning in patient's diary) measured by the 11-point NRS (NRS, 0=no pain, 10=maximum pain imaginable) of the BPI from baseline (1 week before randomisation) to 24 weeks after the first administration.
次要结局
- Assessment of BoNT-A effects in reducing neuropathic symptoms with VAS.(25 weeks)
- Assessment of the therapeutic gain of BoNT-A in terms of relief of spontaneous pain(25 weeks)
- Assessment of BoNT-A effects in reducing neuropathic symptoms with Bedside Sensory Assessment.(25 weeks)
- Assessment of BoNT-A impact on patient's quality of life.(25 weeks)
- Assessment of BoNT-A effects in reducing neuropathic symptoms with the Neuropathic Pain Symptom Inventory .(25 weeks)
- Assessment of BoNT-A safety(24 weeks)
研究者
Francesco Bono
Principal Investigator
Azienda Ospedaliera Universitaria Mater Domini, Catanzaro