Nabilone 和 THC/CBD 用于治疗 FBSS 难治性疼痛
研究概览
详细说明
背部手术失败综合症 (FBSS) 定义为:来源不明的脊柱疼痛,尽管进行了手术干预但仍持续存在,或者在手术干预后出现最初位于同一地形位置的脊柱疼痛。
几种情况已被确定为 FBSS 的原因:硬膜外纤维化、椎管狭窄(整体或外侧)、椎间孔狭窄、椎间盘碎片残留、复发性椎间盘突出或退化、脊柱不稳定、小关节疼痛、骶髂关节疼痛、椎间盘炎、粘连性蛛网膜炎和其他。
可涉及 20% 至 40% 的接受过腰椎手术的患者和 0.02% 至 2% 的普通人群患有此综合征。
在 FBSS 中,症状是腰痛的持续存在、神经根病的恶化或复发、感觉和/或运动缺陷、括约肌功能障碍。
慢性阿片类药物治疗不会改善长期疼痛管理。 类似的问题可能会发生在硬膜外注射类固醇、鞘内输注镇痛剂和局部麻醉剂注射等保守措施中。 尽管有很大一部分 FBSS 患者受益于射频治疗和/或脊髓刺激 (SCS),但其中一小部分患者并未报告获益。
疼痛可以通过调节内源性大麻素系统的药物来治疗,它可以代表神经性疼痛的多模式治疗方法中的一种药理学选择。
作者提出了一个回顾性病例系列,记录了 20 名 FBSS 患者口服大麻素激动剂(THC/CBD 和萘比隆)的疗效和安全性,这些患者表现出对其他治疗方案无反应的中度至重度慢性疼痛。
大麻素激动剂的给药与脊髓刺激 (SCS) 的实践有关。
在治疗开始前停止其他镇痛治疗。
该研究于2014年9月至2016年1月期间进行,持续时间长达12个月。
使用 Douleur Neuropathique 4 问卷测量神经性疼痛的特征和严重程度。 Brief Pain Inventory 允许患者评估他们疼痛的严重程度以及疼痛对感觉和功能的一般维度的干扰程度。
患者年龄在 45 至 69 岁之间。 所有患者均接受固定剂量的大麻素激动剂:治疗开始时使用萘比龙 1 毫克/天或用于口服 THC/CBD 25 毫克/天的油酸混悬液。
基础剂量的增加取决于对疼痛控制的影响。 通过减少下标剂量来处理不良反应。 如果不良事件需要暂停最初处方药的给药,则将其转换为研究中可用的另一种药物。
研究类型
注册 (实际的)
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
纳入标准:
- FBSS 伴难治性疼痛
- DN-4 得分为 4 或 +
排除标准:
- 药物不良反应
- 受试者患有 FBSS,无法退出之前的药物治疗
学习计划
研究是如何设计的?
设计细节
- 观测模型:队列
- 时间观点:追溯
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
|
萘比隆
受失败背部手术综合症 (FBSS) 影响的患者
|
其他名称:
|
|
四氢大麻酚/生物多样性公约
受失败背部手术综合症 (FBSS) 影响的患者
|
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
简要疼痛量表 (BPI)
大体时间:2015/1 至 2016/1
|
Brief Pain Inventory 允许患者评估他们疼痛的严重程度以及他们的疼痛对感觉和功能的一般维度的干扰程度。
BPI 已被证明是衡量由广泛的临床状况引起的疼痛的适当措施。
BPI 是一份包含 11 个项目的问卷,由四个 0 到 10 的数字评定量表 (NRS) 项目组成,要求患者在“过去 24 小时内最严重”、“过去 24 小时内最轻”时对他们的疼痛进行评分, “平均”和“现在”,0 表示“无痛”,10 表示“你能想象到的那么痛”。
其余七个 BPI 项目探讨疼痛对一般活动、情绪、行走能力、正常工作、与他人的关系、睡眠和生活享受的干扰程度,同样使用 0 到 10 的数值量表。
对于这些干扰项,0代表“不干扰”,10代表“完全干扰”。
|
2015/1 至 2016/1
|
|
Douleur 神经病 4 (DN-4)
大体时间:2015/1 至 2016/1
|
DN4问卷共10个项目:7个项目与疼痛的特征(灼痛、冷痛、电击)及其与异常感觉的关联(刺痛、针刺、麻木、瘙痒)相关,3个与疼痛相关疼痛区域的神经系统检查(触摸感觉减退,针刺感觉减退,触觉异常性疼痛)。
每个正项赋值为 1,每个负项赋值为 0。
总分计算为所有 10 个项目的总和,神经性疼痛诊断的临界值确定为总分 4/10。
|
2015/1 至 2016/1
|
合作者和调查者
调查人员
- 首席研究员:Domenico Quattrone, MD、S. Vincenzo Hospital ASP Messina
出版物和有用的链接
一般刊物
- Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011 Nov;72(5):735-44. doi: 10.1111/j.1365-2125.2011.03970.x.
- Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.
- Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, Haythornthwaite JA, Jensen MP, Kerns RD, Ader DN, Brandenburg N, Burke LB, Cella D, Chandler J, Cowan P, Dimitrova R, Dionne R, Hertz S, Jadad AR, Katz NP, Kehlet H, Kramer LD, Manning DC, McCormick C, McDermott MP, McQuay HJ, Patel S, Porter L, Quessy S, Rappaport BA, Rauschkolb C, Revicki DA, Rothman M, Schmader KE, Stacey BR, Stauffer JW, von Stein T, White RE, Witter J, Zavisic S. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008 Feb;9(2):105-21. doi: 10.1016/j.jpain.2007.09.005. Epub 2007 Dec 11.
- Walitt B, Klose P, Fitzcharles MA, Phillips T, Hauser W. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev. 2016 Jul 18;7(7):CD011694. doi: 10.1002/14651858.CD011694.pub2.
- Peul WC, van Houwelingen HC, van den Hout WB, Brand R, Eekhof JA, Tans JT, Thomeer RT, Koes BW; Leiden-The Hague Spine Intervention Prognostic Study Group. Surgery versus prolonged conservative treatment for sciatica. N Engl J Med. 2007 May 31;356(22):2245-56. doi: 10.1056/NEJMoa064039.
- Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, Moriello AS, Davis JB, Mechoulam R, Di Marzo V. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001 Oct;134(4):845-52. doi: 10.1038/sj.bjp.0704327.
- Hussain A, Erdek M. Interventional pain management for failed back surgery syndrome. Pain Pract. 2014 Jan;14(1):64-78. doi: 10.1111/papr.12035. Epub 2013 Feb 3.
- Babson KA, Sottile J, Morabito D. Cannabis, Cannabinoids, and Sleep: a Review of the Literature. Curr Psychiatry Rep. 2017 Apr;19(4):23. doi: 10.1007/s11920-017-0775-9.
- Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain. 2006 Apr;7(4):281-9. doi: 10.1016/j.jpain.2005.11.008.
- Burton CV, Kirkaldy-Willis WH, Yong-Hing K, Heithoff KB. Causes of failure of surgery on the lumbar spine. Clin Orthop Relat Res. 1981 Jun;(157):191-9.
- Waguespack A, Schofferman J, Slosar P, Reynolds J. Etiology of long-term failures of lumbar spine surgery. Pain Med. 2002 Mar;3(1):18-22. doi: 10.1046/j.1526-4637.2002.02007.x.
- Slipman CW, Shin CH, Patel RK, Isaac Z, Huston CW, Lipetz JS, Lenrow DA, Braverman DL, Vresilovic EJ Jr. Etiologies of failed back surgery syndrome. Pain Med. 2002 Sep;3(3):200-14; discussion 214-7. doi: 10.1046/j.1526-4637.2002.02033.x.
- Krishna M, Pollock RD, Bhatia C. Incidence, etiology, classification, and management of neuralgia after posterior lumbar interbody fusion surgery in 226 patients. Spine J. 2008 Mar-Apr;8(2):374-9. doi: 10.1016/j.spinee.2006.09.004. Epub 2006 Dec 22.
- Choi HS, Chi EH, Kim MR, Jung J, Lee J, Shin JS, Ha IH. Demographic characteristics and medical service use of failed back surgery syndrome patients at an integrated treatment hospital focusing on complementary and alternative medicine: a retrospective review of electronic medical records. Evid Based Complement Alternat Med. 2014;2014:714389. doi: 10.1155/2014/714389. Epub 2014 Nov 4.
- Shapiro CM. The failed back surgery syndrome: pitfalls surrounding evaluation and treatment. Phys Med Rehabil Clin N Am. 2014 May;25(2):319-40. doi: 10.1016/j.pmr.2014.01.014.
- Thomson S. Failed back surgery syndrome - definition, epidemiology and demographics. Br J Pain. 2013 Feb;7(1):56-9. doi: 10.1177/2049463713479096.
- Chan CW, Peng P. Failed back surgery syndrome. Pain Med. 2011 Apr;12(4):577-606. doi: 10.1111/j.1526-4637.2011.01089.x. Epub 2011 Apr 4.
- Khosravi MB, Azemati S, Sahmeddini MA. Gabapentin versus naproxen in the management of failed back surgery syndrome; a randomized controlled trial. Acta Anaesthesiol Belg. 2014;65(1):31-7.
- Zencirci B. Analgesic efficacy of oral gabapentin added to standard epidural corticosteroids in patients with failed back surgery. Clin Pharmacol. 2010;2:207-11. doi: 10.2147/CPAA.S12126. Epub 2010 Sep 30.
- Abeloos L, De Witte O, Riquet R, Tuna T, Mathieu N. [Long-term outcome of patients treated with spinal cord stimulation for therapeutically refractory failed back surgery syndrome: a retrospective study]. Neurochirurgie. 2011 Jul;57(3):114-9. doi: 10.1016/j.neuchi.2011.07.001. Epub 2011 Sep 9. French.
- Van Buyten JP, Al-Kaisy A, Smet I, Palmisani S, Smith T. High-frequency spinal cord stimulation for the treatment of chronic back pain patients: results of a prospective multicenter European clinical study. Neuromodulation. 2013 Jan-Feb;16(1):59-65; discussion 65-6. doi: 10.1111/ner.12006. Epub 2012 Nov 30.
- North RB, Kidd D, Shipley J, Taylor RS. Spinal cord stimulation versus reoperation for failed back surgery syndrome: a cost effectiveness and cost utility analysis based on a randomized, controlled trial. Neurosurgery. 2007 Aug;61(2):361-8; discussion 368-9. doi: 10.1227/01.NEU.0000255522.42579.EA. Erratum In: Neurosurgery. 2009 Apr;64(4):601.
- Sciubba DM, Gokaslan ZL. Spinal cord stimulation for failed back surgery syndrome--does it work and is it cost-effective? Nat Clin Pract Neurol. 2008 Sep;4(9):472-3. doi: 10.1038/ncpneuro0865. Epub 2008 Jul 22.
- Boswell MV, Hansen HC, Trescot AM, Hirsch JA. Epidural steroids in the management of chronic spinal pain and radiculopathy. Pain Physician. 2003 Jul;6(3):319-34.
- Kim SB, Lee KW, Lee JH, Kim MA, An BW. The effect of hyaluronidase in interlaminar lumbar epidural injection for failed back surgery syndrome. Ann Rehabil Med. 2012 Aug;36(4):466-73. doi: 10.5535/arm.2012.36.4.466. Epub 2012 Aug 27.
- Kumar K, Hunter G, Demeria DD. Treatment of chronic pain by using intrathecal drug therapy compared with conventional pain therapies: a cost-effectiveness analysis. J Neurosurg. 2002 Oct;97(4):803-10. doi: 10.3171/jns.2002.97.4.0803.
- Tomycz ND, Ortiz V, Moossy JJ. Simultaneous intrathecal opioid pump and spinal cord stimulation for pain management: analysis of 11 patients with failed back surgery syndrome. J Pain Palliat Care Pharmacother. 2010 Dec;24(4):374-83. doi: 10.3109/15360288.2010.523066.
- Wong CB, Chen WJ, Chen LH, Niu CC, Lai PL. Clinical outcomes of revision lumbar spinal surgery: 124 patients with a minimum of two years of follow-up. Chang Gung Med J. 2002 Mar;25(3):175-82.
- Duggal N, Mendiondo I, Pares HR, Jhawar BS, Das K, Kenny KJ, Dickman CA. Anterior lumbar interbody fusion for treatment of failed back surgery syndrome: an outcome analysis. Neurosurgery. 2004 Mar;54(3):636-43; discussion 643-4. doi: 10.1227/01.neu.0000108423.87889.9e.
- Kat'uch V, Pataky F, Kat'uchova J, Gajdos M, Radonak J. [Surgical management of the failed back surgery syndrome (FBSS) using posterior lumbar interbody fusion (PLIF) with posterior transpedicular stabilization]. Rozhl Chir. 2010 Aug;89(7):450-8. Slovak.
- Simon A, Seizeur R, Person H, Forlodou P, Dam Hieu P, Besson G. [Anterior lumbar interbody fusion for treatment of failed back surgery syndrome: a retrospective study of 46 cases]. Neurochirurgie. 2009 Jun;55(3):309-13. doi: 10.1016/j.neuchi.2008.09.003. Epub 2008 Dec 16. French.
- Esmer G, Blum J, Rulf J, Pier J. Mindfulness-based stress reduction for failed back surgery syndrome: a randomized controlled trial. J Am Osteopath Assoc. 2010 Nov;110(11):646-52. Erratum In: J Am Osteopath Assoc. 2011 Jan;111(1):3. J Am Osteopath Assoc. 2011 Jul;111(7):424.
- Manniche C, Asmussen K, Lauritsen B, Vinterberg H, Karbo H, Abildstrup S, Fischer-Nielsen K, Krebs R, Ibsen K. Intensive dynamic back exercises with or without hyperextension in chronic back pain after surgery for lumbar disc protrusion. A clinical trial. Spine (Phila Pa 1976). 1993 Apr;18(5):560-7. doi: 10.1097/00007632-199304000-00007.
- Katz JA, Swerdloff MA, Brass SD, Argoff CE, Markman J, Backonja M, Katz N. Opioids for chronic noncancer pain: A position paper of the American Academy of Neurology. Neurology. 2015 Apr 7;84(14):1503-4. doi: 10.1212/WNL.0000000000001485. No abstract available.
- Attal N, Bouhassira D. Pharmacotherapy of neuropathic pain: which drugs, which treatment algorithms? Pain. 2015 Apr;156 Suppl 1:S104-S114. doi: 10.1097/01.j.pain.0000460358.01998.15.
- Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010 Aug;9(8):807-19. doi: 10.1016/S1474-4422(10)70143-5.
- Maier C, Baron R, Sommer C. [Neuropathic pain. How to open the blackbox]. Schmerz. 2015 Oct;29(5):479-80, 482-5. doi: 10.1007/s00482-015-0028-y. German.
- Baber Z, Erdek MA. Failed back surgery syndrome: current perspectives. J Pain Res. 2016 Nov 7;9:979-987. doi: 10.2147/JPR.S92776. eCollection 2016.
- Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010 Sep;150(3):573-581. doi: 10.1016/j.pain.2010.06.019.
- O'Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med. 2009 Oct;122(10 Suppl):S22-32. doi: 10.1016/j.amjmed.2009.04.007.
- Lynch ME, Ware MA. Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials. J Neuroimmune Pharmacol. 2015 Jun;10(2):293-301. doi: 10.1007/s11481-015-9600-6. Epub 2015 Mar 22.
- Tsang CC, Giudice MG. Nabilone for the Management of Pain. Pharmacotherapy. 2016 Mar;36(3):273-86. doi: 10.1002/phar.1709. Epub 2016 Feb 29.
- Atkinson TM, Rosenfeld BD, Sit L, Mendoza TR, Fruscione M, Lavene D, Shaw M, Li Y, Hay J, Cleeland CS, Scher HI, Breitbart WS, Basch E. Using confirmatory factor analysis to evaluate construct validity of the Brief Pain Inventory (BPI). J Pain Symptom Manage. 2011 Mar;41(3):558-65. doi: 10.1016/j.jpainsymman.2010.05.008. Epub 2010 Dec 4.
- Ware MA, Doyle CR, Woods R, Lynch ME, Clark AJ. Cannabis use for chronic non-cancer pain: results of a prospective survey. Pain. 2003 Mar;102(1-2):211-6. doi: 10.1016/s0304-3959(02)00400-1.
- Pertwee RG. Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities. Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5;367(1607):3353-63. doi: 10.1098/rstb.2011.0381.
- Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014 Feb;46(1):86-95. doi: 10.3109/03602532.2013.849268. Epub 2013 Oct 25.
- Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl). 1982;76(3):245-50. doi: 10.1007/BF00432554.
- Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic Biol Med. 2011 Sep 1;51(5):1054-61. doi: 10.1016/j.freeradbiomed.2011.01.007. Epub 2011 Jan 14.
- Fernandez-Ruiz J, Sagredo O, Pazos MR, Garcia C, Pertwee R, Mechoulam R, Martinez-Orgado J. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? Br J Clin Pharmacol. 2013 Feb;75(2):323-33. doi: 10.1111/j.1365-2125.2012.04341.x.
- Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci. 2009 Oct;30(10):515-27. doi: 10.1016/j.tips.2009.07.006. Epub 2009 Sep 2. Erratum In: Trends Pharmacol Sci. 2009 Dec;30(12):609.
- Hayakawa K, Mishima K, Hazekawa M, Sano K, Irie K, Orito K, Egawa T, Kitamura Y, Uchida N, Nishimura R, Egashira N, Iwasaki K, Fujiwara M. Cannabidiol potentiates pharmacological effects of Delta(9)-tetrahydrocannabinol via CB(1) receptor-dependent mechanism. Brain Res. 2008 Jan 10;1188:157-64. doi: 10.1016/j.brainres.2007.09.090. Epub 2007 Oct 12.
- Casarotto PC, Gomes FV, Resstel LB, Guimaraes FS. Cannabidiol inhibitory effect on marble-burying behaviour: involvement of CB1 receptors. Behav Pharmacol. 2010 Jul;21(4):353-8. doi: 10.1097/fbp.0b013e32833b33c5.
- Ryberg E, Larsson N, Sjogren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2007 Dec;152(7):1092-101. doi: 10.1038/sj.bjp.0707460. Epub 2007 Sep 17.
- Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005 Aug;30(8):1037-43. doi: 10.1007/s11064-005-6978-1.
- Pazos MR, Mohammed N, Lafuente H, Santos M, Martinez-Pinilla E, Moreno E, Valdizan E, Romero J, Pazos A, Franco R, Hillard CJ, Alvarez FJ, Martinez-Orgado J. Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs: role of 5HT(1A) and CB2 receptors. Neuropharmacology. 2013 Aug;71:282-91. doi: 10.1016/j.neuropharm.2013.03.027. Epub 2013 Apr 12.
- Kathmann M, Flau K, Redmer A, Trankle C, Schlicker E. Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn Schmiedebergs Arch Pharmacol. 2006 Feb;372(5):354-61. doi: 10.1007/s00210-006-0033-x. Epub 2006 Feb 18.
- Esposito G, Scuderi C, Valenza M, Togna GI, Latina V, De Filippis D, Cipriano M, Carratu MR, Iuvone T, Steardo L. Cannabidiol reduces Abeta-induced neuroinflammation and promotes hippocampal neurogenesis through PPARgamma involvement. PLoS One. 2011;6(12):e28668. doi: 10.1371/journal.pone.0028668. Epub 2011 Dec 5.
- Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimaraes FS. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5;367(1607):3364-78. doi: 10.1098/rstb.2011.0389.
- Costa B, Giagnoni G, Franke C, Trovato AE, Colleoni M. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation. Br J Pharmacol. 2004 Sep;143(2):247-50. doi: 10.1038/sj.bjp.0705920. Epub 2004 Aug 16.
- Blumenthal DE, Malemud CJ. Recent strategies for drug development in fibromyalgia syndrome. Expert Rev Neurother. 2016 Dec;16(12):1407-1411. doi: 10.1080/14737175.2016.1207531. Epub 2016 Jul 14.
- Clark AJ, Lynch ME, Ware M, Beaulieu P, McGilveray IJ, Gourlay D. Guidelines for the use of cannabinoid compounds in chronic pain. Pain Res Manag. 2005 Autumn;10 Suppl A:44A-6A. doi: 10.1155/2005/894781.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.