Department of Anesthesia, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, H3G 1Y6, Canada.
Alan Edwards Pain Management Unit, McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada.
Trials. 2021 Feb 17;22(1):149. doi: 10.1186/s13063-021-05088-w.
First-line pharmacotherapy for neuropathic pain entails the use of systemic antidepressants and anticonvulsants. These drugs are not optimally effective and poorly tolerated, especially for older patients with comorbid conditions. Given the high number of such patients, there is a need for a greater repertoire of safer and more effective analgesics. Clonidine and pentoxifylline are vasodilator agents that work synergistically to enhance tissue perfusion and oxygenation. The topical administration of these drugs, individually and in combination, has shown anti-nociceptive properties in rodent models of neuropathic pain. A topically-administered combination of clonidine and pentoxifylline also effectively reduced the intensity of both spontaneous and evoked pain in healthy volunteers with experimentally-induced neuropathic pain. The next step in advancing this formulation to clinical use is the undertaking of a phase II clinical study to assess its efficacy and safety in neuropathic pain patients.
METHODS/DESIGN: This is a study protocol for a randomized, double-blind, placebo-controlled, phase II clinical trial with a cross-over design. It is a single-centered, 5-week study that will enroll a total of 32 patients with post-traumatic peripheral neuropathic pain. Patients will be treated topically with either a combination of clonidine and pentoxifylline or placebo for a period of 2 weeks each, in randomly assigned order across patients, with an intervening washout period of 1 week. The primary outcome measures of the study are the intensity of spontaneous pain recorded daily in a pain diary with a visual analog scale, and the degree of mechanical allodynia evoked by a brush stimulus. The secondary outcome measures of the study include scores of pain relief and change in the area of punctate hyperalgesia. This trial has been prospectively registered with ClinicalTrials.gov on November 1, 2017. ClinicalTrials.gov Identifier: NCT03342950 .
The analgesic use of topical treatment with clonidine and pentoxifylline in combination has not been investigated in post-traumatic neuropathic pain. This study could generate the first evidence for the efficacy and safety of the formulation in alleviating pain in patients with neuropathic pain. Furthermore, this trial will provide objective grounds for the investigation of other agents that enhance tissue oxygenation in the topical treatment of peripheral neuropathic pain.
This trial has been registered with ClinicalTrials.gov owned by NIH's US National Library of Medicine. ClinicalTrials.gov NCT03342950 . Registered on November 1, 2017 (trial was prospectively registered).
This is protocol version 5, dated June 2018. McGill University Health Center (MUHC) Reaseach Ethics Board (REB) identification number: TTNP 2018-3906.
治疗神经性疼痛的一线药物治疗需要使用全身抗抑郁药和抗惊厥药。这些药物的疗效并不理想，耐受性也较差，尤其是对伴有合并症的老年患者。鉴于此类患者数量众多，需要更多安全有效的镇痛药物。可乐定和己酮可可碱是血管扩张剂，它们协同作用增强组织灌注和氧合。这些药物的局部给药，单独使用和联合使用，在神经性疼痛的啮齿动物模型中显示出抗伤害感受特性。局部给予可乐定和己酮可可碱的组合也能有效减轻实验性诱导神经性疼痛的健康志愿者的自发性和诱发性疼痛的强度。将该制剂推进临床使用的下一步是进行一项 II 期临床试验，以评估其在神经性疼痛患者中的疗效和安全性。
方法/设计：这是一项采用随机、双盲、安慰剂对照、交叉设计的 II 期临床试验研究方案。这是一项单中心、为期 5 周的研究，共纳入 32 例创伤后周围神经性疼痛患者。患者将被随机分配，以患者为单位，分别接受为期 2 周的可乐定和己酮可可碱联合治疗或安慰剂治疗，期间间隔 1 周洗脱期。研究的主要结局指标是用视觉模拟量表(VAS)记录的每日自发性疼痛强度，以及用毛刷刺激诱发的机械性感觉过敏程度。研究的次要结局指标包括疼痛缓解评分和点状痛觉过敏面积的变化。这项试验于 2017 年 11 月 1 日在 ClinicalTrials.gov 上进行了前瞻性注册。ClinicalTrials.gov 标识符：NCT03342950。
局部使用可乐定和己酮可可碱联合治疗在创伤后神经性疼痛中的应用尚未得到研究。本研究可能为该制剂在缓解神经性疼痛患者疼痛方面的疗效和安全性提供首个证据。此外，这项试验将为研究其他增强组织氧合的药物在周围神经性疼痛的局部治疗中的应用提供客观依据。
这项试验已在 NIH 美国国立医学图书馆拥有的 ClinicalTrials.gov 上注册。ClinicalTrials.gov NCT03342950。于 2017 年 11 月 1 日注册（试验前瞻性注册）。
这是 2018 年 6 月的第 5 版方案。麦吉尔大学健康中心（MUHC）研究伦理委员会（REB）编号：TTNP 2018-3906。
