drugset / Trial / NCT02736890
Injecting Botulinum Toxin A Underneath the Skin to Treat Spinal Cord Pain in Patients With Spinal Cord Injury
RandomizedCrossoverDouble-blindTreatment
Summary
Back pain is a common secondary condition of both acute and chronic spinal cord injury (SCI). Current existing treatment including both pharmacologic and non-pharmacologic are limited by marginal efficacy or intolerable side effects. The purpose of this study is to evaluate the potential of subcutaneous injections of botulinum toxin A to provide pain relief in spinal cord injury patients with back pain near the level of injury in the spine. Botulinum toxin A has been shown in both pre-clinical and clinical studies to help with nerve pain. The researchers propose a double blinded placebo controlled crossover study to study the effects of subcutaneous botulinum injections to at--level SCI back pain in patients with spinal cord injury.
Timeline
- Start
- 2016-03
- Primary completion
- 2018-07-17
- Completion
- 2018-07-17
Publications
- Background Siddall PJ, McClelland JM, Rutkowski SB, Cousins MJ. A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury. Pain. 2003 Jun;103(3):249-257. doi: 10.1016/S0304-3959(02)00452-9.
- Background Cardenas DD, Bryce TN, Shem K, Richards JS, Elhefni H. Gender and minority differences in the pain experience of people with spinal cord injury. Arch Phys Med Rehabil. 2004 Nov;85(11):1774-81. doi: 10.1016/j.apmr.2004.04.027.
- Background Rintala DH, Loubser PG, Castro J, Hart KA, Fuhrer MJ. Chronic pain in a community-based sample of men with spinal cord injury: prevalence, severity, and relationship with impairment, disability, handicap, and subjective well-being. Arch Phys Med Rehabil. 1998 Jun;79(6):604-14. doi: 10.1016/s0003-9993(98)90032-6.
- Background Jensen MP, Hoffman AJ, Cardenas DD. Chronic pain in individuals with spinal cord injury: a survey and longitudinal study. Spinal Cord. 2005 Dec;43(12):704-12. doi: 10.1038/sj.sc.3101777.
- Background Vogel LC, Krajci KA, Anderson CJ. Adults with pediatric-onset spinal cord injury: part 2: musculoskeletal and neurological complications. J Spinal Cord Med. 2002 Summer;25(2):117-23. doi: 10.1080/10790268.2002.11753611.
- Background McColl MA, Charlifue S, Glass C, Lawson N, Savic G. Aging, gender, and spinal cord injury. Arch Phys Med Rehabil. 2004 Mar;85(3):363-7. doi: 10.1016/j.apmr.2003.06.022.
- Background Knutsdottir S. Spinal cord injuries in Iceland 1973-1989. A follow up study. Paraplegia. 1993 Jan;31(1):68-72. doi: 10.1038/sc.1993.10.
- Background Samuelsson KK. Back pain and spinal Deformity-Common among wheelchair users with spinal cord injuries. Scandinavian journal of occupational therapy. 1996 -01;3(1):28-32.
- Background Waisbrod H, Hansen D, Gerbershagen HU. Chronic pain in paraplegics. Neurosurgery. 1984 Dec;15(6):933-4.
- Background Hardcastle P, Bedbrook G, Curtis K. Long-term results of conservative and operative management in complete paraplegics with spinal cord injuries between T10 and L2 with respect to function. Clin Orthop Relat Res. 1987 Nov;(224):88-96.
- Background Walter JS, Sacks J, Othman R, Rankin AZ, Nemchausky B, Chintam R, Wheeler JS. A database of self-reported secondary medical problems among VA spinal cord injury patients: its role in clinical care and management. J Rehabil Res Dev. 2002 Jan-Feb;39(1):53-61.
- Background Rintala DH, Hart KA, Priebe MM. Predicting consistency of pain over a 10-year period in persons with spinal cord injury. J Rehabil Res Dev. 2004 Jan-Feb;41(1):75-88. doi: 10.1682/jrrd.2004.01.0075.
- Background Cardenas DD, Jensen MP. Treatments for chronic pain in persons with spinal cord injury: A survey study. J Spinal Cord Med. 2006;29(2):109-17. doi: 10.1080/10790268.2006.11753864.
- Background Cardenas DD, Warms CA, Turner JA, Marshall H, Brooke MM, Loeser JD. Efficacy of amitriptyline for relief of pain in spinal cord injury: results of a randomized controlled trial. Pain. 2002 Apr;96(3):365-373. doi: 10.1016/S0304-3959(01)00483-3.
- Background Levendoglu F, Ogun CO, Ozerbil O, Ogun TC, Ugurlu H. Gabapentin is a first line drug for the treatment of neuropathic pain in spinal cord injury. Spine (Phila Pa 1976). 2004 Apr 1;29(7):743-51. doi: 10.1097/01.brs.0000112068.16108.3a.
- Background Norrbrink C, Lundeberg T. Tramadol in neuropathic pain after spinal cord injury: a randomized, double-blind, placebo-controlled trial. Clin J Pain. 2009 Mar-Apr;25(3):177-84. doi: 10.1097/AJP.0b013e31818a744d.
- Background Elia AE, Filippini G, Calandrella D, Albanese A. Botulinum neurotoxins for post-stroke spasticity in adults: a systematic review. Mov Disord. 2009 Apr 30;24(6):801-12. doi: 10.1002/mds.22452.
- Background Novak I, Campbell L, Boyce M, Fung VS; Cerebral Palsy Institute. Botulinum toxin assessment, intervention and aftercare for cervical dystonia and other causes of hypertonia of the neck: international consensus statement. Eur J Neurol. 2010 Aug;17 Suppl 2:94-108. doi: 10.1111/j.1468-1331.2010.03130.x.
- Background Sheean G, Lannin NA, Turner-Stokes L, Rawicki B, Snow BJ; Cerebral Palsy Institute. Botulinum toxin assessment, intervention and after-care for upper limb hypertonicity in adults: international consensus statement. Eur J Neurol. 2010 Aug;17 Suppl 2:74-93. doi: 10.1111/j.1468-1331.2010.03129.x.
- Background Olver J, Esquenazi A, Fung VS, Singer BJ, Ward AB; Cerebral Palsy Institute. Botulinum toxin assessment, intervention and aftercare for lower limb disorders of movement and muscle tone in adults: international consensus statement. Eur J Neurol. 2010 Aug;17 Suppl 2:57-73. doi: 10.1111/j.1468-1331.2010.03128.x.
- Background Piovesan EJ, Teive HG, Kowacs PA, Della Coletta MV, Werneck LC, Silberstein SD. An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology. 2005 Oct 25;65(8):1306-8. doi: 10.1212/01.wnl.0000180940.98815.74.
- Background Xiao L, Mackey S, Hui H, Xong D, Zhang Q, Zhang D. Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. Pain Med. 2010 Dec;11(12):1827-33. doi: 10.1111/j.1526-4637.2010.01003.x.
- Background Wu CJ, Lian YJ, Zheng YK, Zhang HF, Chen Y, Xie NC, Wang LJ. Botulinum toxin type A for the treatment of trigeminal neuralgia: results from a randomized, double-blind, placebo-controlled trial. Cephalalgia. 2012 Apr;32(6):443-50. doi: 10.1177/0333102412441721. Epub 2012 Apr 5.
- Background Yuan RY, Sheu JJ, Yu JM, Chen WT, Tseng IJ, Chang HH, Hu CJ. Botulinum toxin for diabetic neuropathic pain: a randomized double-blind crossover trial. Neurology. 2009 Apr 28;72(17):1473-8. doi: 10.1212/01.wnl.0000345968.05959.cf. Epub 2009 Feb 25.
- Background Jabbari B, Maher N, Difazio MP. Botulinum toxin a improved burning pain and allodynia in two patients with spinal cord pathology. Pain Med. 2003 Jun;4(2):206-10. doi: 10.1046/j.1526-4637.2003.03013.x.
- Background Bryce TN, Budh CN, Cardenas DD, Dijkers M, Felix ER, Finnerup NB, Kennedy P, Lundeberg T, Richards JS, Rintala DH, Siddall P, Widerstrom-Noga E. Pain after spinal cord injury: an evidence-based review for clinical practice and research. Report of the National Institute on Disability and Rehabilitation Research Spinal Cord Injury Measures meeting. J Spinal Cord Med. 2007;30(5):421-40. doi: 10.1080/10790268.2007.11753405.
- Background Bryce TN, Biering-Sorensen F, Finnerup NB, Cardenas DD, Defrin R, Ivan E, Lundeberg T, Norrbrink C, Richards JS, Siddall P, Stripling T, Treede RD, Waxman SG, Widerstrom-Noga E, Yezierski RP, Dijkers M. International Spinal Cord Injury Pain (ISCIP) Classification: Part 2. Initial validation using vignettes. Spinal Cord. 2012 Jun;50(6):404-12. doi: 10.1038/sc.2012.2. Epub 2012 Feb 7.
- Background Bryce TN, Ragnarsson KT. Pain after spinal cord injury. Phys Med Rehabil Clin N Am. 2000 Feb;11(1):157-68.
- Background Vranken JH, Hollmann MW, van der Vegt MH, Kruis MR, Heesen M, Vos K, Pijl AJ, Dijkgraaf MGW. Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial. Pain. 2011 Feb;152(2):267-273. doi: 10.1016/j.pain.2010.09.005.
- Background Lis AM, Black KM, Korn H, Nordin M. Association between sitting and occupational LBP. Eur Spine J. 2007 Feb;16(2):283-98. doi: 10.1007/s00586-006-0143-7. Epub 2006 May 31.
- Background Van Nieuwenhuyse A, Fatkhutdinova L, Verbeke G, Pirenne D, Johannik K, Somville PR, Mairiaux P, Moens GF, Masschelein R. Risk factors for first-ever low back pain among workers in their first employment. Occup Med (Lond). 2004 Dec;54(8):513-9. doi: 10.1093/occmed/kqh091. Epub 2004 Sep 22.
- Background Adams MA, McNally DS, Chinn H, Dolan P. The clinical biomechanics award paper 1993 Posture and the compressive strength of the lumbar spine. Clin Biomech (Bristol). 1994 Jan;9(1):5-14. doi: 10.1016/0268-0033(94)90052-3.
- Background Panjabi MM, Andersson GB, Jorneus L, Hult E, Mattsson L. In vivo measurements of spinal column vibrations. J Bone Joint Surg Am. 1986 Jun;68(5):695-702.
- Background Scannell JP, McGill SM. Lumbar posture--should it, and can it, be modified? A study of passive tissue stiffness and lumbar position during activities of daily living. Phys Ther. 2003 Oct;83(10):907-17.
- Background Claus AP, Hides JA, Moseley GL, Hodges PW. Is 'ideal' sitting posture real? Measurement of spinal curves in four sitting postures. Man Ther. 2009 Aug;14(4):404-8. doi: 10.1016/j.math.2008.06.001. Epub 2008 Sep 14.
- Background Dunk NM, Kedgley AE, Jenkyn TR, Callaghan JP. Evidence of a pelvis-driven flexion pattern: are the joints of the lower lumbar spine fully flexed in seated postures? Clin Biomech (Bristol). 2009 Feb;24(2):164-8. doi: 10.1016/j.clinbiomech.2008.12.003. Epub 2009 Jan 12.
- Background De Carvalho DE, Soave D, Ross K, Callaghan JP. Lumbar spine and pelvic posture between standing and sitting: a radiologic investigation including reliability and repeatability of the lumbar lordosis measure. J Manipulative Physiol Ther. 2010 Jan;33(1):48-55. doi: 10.1016/j.jmpt.2009.11.008.
- Background Dolan P, Adams MA, Hutton WC. Commonly adopted postures and their effect on the lumbar spine. Spine (Phila Pa 1976). 1988 Feb;13(2):197-201. doi: 10.1097/00007632-198802000-00012.
- Background Lord MJ, Small JM, Dinsay JM, Watkins RG. Lumbar lordosis. Effects of sitting and standing. Spine (Phila Pa 1976). 1997 Nov 1;22(21):2571-4. doi: 10.1097/00007632-199711010-00020.
- Background Callaghan JP, McGill SM. Low back joint loading and kinematics during standing and unsupported sitting. Ergonomics. 2001 Feb 20;44(3):280-94. doi: 10.1080/00140130118276.
- Background Harrison DD, Harrison SO, Croft AC, Harrison DE, Troyanovich SJ. Sitting biomechanics part I: review of the literature. J Manipulative Physiol Ther. 1999 Nov-Dec;22(9):594-609. doi: 10.1016/s0161-4754(99)70020-5.
- Background Hedman TP, Fernie GR. Mechanical response of the lumbar spine to seated postural loads. Spine (Phila Pa 1976). 1997 Apr 1;22(7):734-43. doi: 10.1097/00007632-199704010-00004.
- Background Reeve A, Dilley A. Effects of posture on the thickness of transversus abdominis in pain-free subjects. Man Ther. 2009 Dec;14(6):679-84. doi: 10.1016/j.math.2009.02.008. Epub 2009 May 14.
- Background Claus AP, Hides JA, Moseley GL, Hodges PW. Different ways to balance the spine: subtle changes in sagittal spinal curves affect regional muscle activity. Spine (Phila Pa 1976). 2009 Mar 15;34(6):E208-14. doi: 10.1097/BRS.0b013e3181908ead.
- Background O'Sullivan PB, Dankaerts W, Burnett AF, Farrell GT, Jefford E, Naylor CS, O'Sullivan KJ. Effect of different upright sitting postures on spinal-pelvic curvature and trunk muscle activation in a pain-free population. Spine (Phila Pa 1976). 2006 Sep 1;31(19):E707-12. doi: 10.1097/01.brs.0000234735.98075.50.
- Background Francisco GE, Tan H, Green M. Do botulinum toxins have a role in the management of neuropathic pain?: a focused review. Am J Phys Med Rehabil. 2012 Oct;91(10):899-909. doi: 10.1097/PHM.0b013e31825a134b.
- Background Lu DW, Lippitz J. Complications of botulinum neurotoxin. Dis Mon. 2009 Apr;55(4):198-211. doi: 10.1016/j.disamonth.2009.01.001. No abstract available.
- Background Argoff CE. A focused review on the use of botulinum toxins for neuropathic pain. Clin J Pain. 2002 Nov-Dec;18(6 Suppl):S177-81. doi: 10.1097/00002508-200211001-00010.
- Background Matak I, Bach-Rojecky L, Filipovic B, Lackovic Z. Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin A. Neuroscience. 2011 Jul 14;186:201-7. doi: 10.1016/j.neuroscience.2011.04.026. Epub 2011 Apr 20.
- Background Foster L, Clapp L, Erickson M, Jabbari B. Botulinum toxin A and chronic low back pain: a randomized, double-blind study. Neurology. 2001 May 22;56(10):1290-3. doi: 10.1212/wnl.56.10.1290.
- Background Apalla Z, Sotiriou E, Lallas A, Lazaridou E, Ioannides D. Botulinum toxin A in postherpetic neuralgia: a parallel, randomized, double-blind, single-dose, placebo-controlled trial. Clin J Pain. 2013 Oct;29(10):857-64. doi: 10.1097/AJP.0b013e31827a72d2.
- Background Ranoux D, Attal N, Morain F, Bouhassira D. Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol. 2008 Sep;64(3):274-83. doi: 10.1002/ana.21427.
- Background Bach-Rojecky L, Salkovic-Petrisic M, Lackovic Z. Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: bilateral effect after unilateral injection. Eur J Pharmacol. 2010 May 10;633(1-3):10-4. doi: 10.1016/j.ejphar.2010.01.020. Epub 2010 Feb 1.
- Background Bach-Rojecky L, Lackovic Z. Central origin of the antinociceptive action of botulinum toxin type A. Pharmacol Biochem Behav. 2009 Dec;94(2):234-8. doi: 10.1016/j.pbb.2009.08.012. Epub 2009 Sep 2.
- Background Kharkar S, Ambady P, Venkatesh Y, Schwartzman RJ. Intramuscular botulinum toxin in complex regional pain syndrome: case series and literature review. Pain Physician. 2011 Sep-Oct;14(5):419-24.
- Background Birthi P, Sloan P, Salles S. Subcutaneous botulinum toxin A for the treatment of refractory complex regional pain syndrome. PM R. 2012 Jun;4(6):446-9. doi: 10.1016/j.pmrj.2011.12.010. No abstract available.
- Background Fabregat G, Asensio-Samper JM, Palmisani S, Villanueva-Perez VL, De Andres J. Subcutaneous botulinum toxin for chronic post-thoracotomy pain. Pain Pract. 2013 Mar;13(3):231-4. doi: 10.1111/j.1533-2500.2012.00569.x. Epub 2012 Jun 21.
- Background Zhang T, Adatia A, Zarin W, Moitri M, Vijenthira A, Chu R, Thabane L, Kean W. The efficacy of botulinum toxin type A in managing chronic musculoskeletal pain: a systematic review and meta analysis. Inflammopharmacology. 2011 Feb;19(1):21-34. doi: 10.1007/s10787-010-0069-x. Epub 2010 Nov 13.
- Background Argoff C. The emerging use of botulinum toxins for the treatment of neuropathic pain. Pain Med. 2010 Dec;11(12):1750-2. doi: 10.1111/j.1526-4637.2010.00997.x. No abstract available.
- Background Lew HL, Lee EH, Castaneda A, Klima R, Date E. Therapeutic use of botulinum toxin type A in treating neck and upper-back pain of myofascial origin: a pilot study. Arch Phys Med Rehabil. 2008 Jan;89(1):75-80. doi: 10.1016/j.apmr.2007.08.133.
- Background Jabbari B, Machado D. Treatment of refractory pain with botulinum toxins--an evidence-based review. Pain Med. 2011 Nov;12(11):1594-606. doi: 10.1111/j.1526-4637.2011.01245.x. Epub 2011 Sep 29.
- Background Jabbari B, Ney J, Sichani A, Monacci W, Foster L, Difazio M. Treatment of refractory, chronic low back pain with botulinum neurotoxin A: an open-label, pilot study. Pain Med. 2006 May-Jun;7(3):260-4. doi: 10.1111/j.1526-4637.2006.00147.x.
- Background McMahon HT, Foran P, Dolly JO, Verhage M, Wiegant VM, Nicholls DG. Tetanus toxin and botulinum toxins type A and B inhibit glutamate, gamma-aminobutyric acid, aspartate, and met-enkephalin release from synaptosomes. Clues to the locus of action. J Biol Chem. 1992 Oct 25;267(30):21338-43.
- Background Welch MJ, Purkiss JR, Foster KA. Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins. Toxicon. 2000 Feb;38(2):245-58. doi: 10.1016/s0041-0101(99)00153-1.
- Background Durham PL, Cady R, Cady R. Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache. 2004 Jan;44(1):35-42; discussion 42-3. doi: 10.1111/j.1526-4610.2004.04007.x.
- Background Meng J, Wang J, Lawrence G, Dolly JO. Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential. J Cell Sci. 2007 Aug 15;120(Pt 16):2864-74. doi: 10.1242/jcs.012211. Epub 2007 Jul 31.
- Background Planells-Cases R, Garcia-Sanz N, Morenilla-Palao C, Ferrer-Montiel A. Functional aspects and mechanisms of TRPV1 involvement in neurogenic inflammation that leads to thermal hyperalgesia. Pflugers Arch. 2005 Oct;451(1):151-9. doi: 10.1007/s00424-005-1423-5. Epub 2005 May 21.
- Background Morenilla-Palao C, Planells-Cases R, Garcia-Sanz N, Ferrer-Montiel A. Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J Biol Chem. 2004 Jun 11;279(24):25665-72. doi: 10.1074/jbc.M311515200. Epub 2004 Apr 5.
- Background Antonucci F, Rossi C, Gianfranceschi L, Rossetto O, Caleo M. Long-distance retrograde effects of botulinum neurotoxin A. J Neurosci. 2008 Apr 2;28(14):3689-96. doi: 10.1523/JNEUROSCI.0375-08.2008.
- Background Restani L, Antonucci F, Gianfranceschi L, Rossi C, Rossetto O, Caleo M. Evidence for anterograde transport and transcytosis of botulinum neurotoxin A (BoNT/A). J Neurosci. 2011 Nov 2;31(44):15650-9. doi: 10.1523/JNEUROSCI.2618-11.2011.
- Background Naumann M, Jankovic J. Safety of botulinum toxin type A: a systematic review and meta-analysis. Curr Med Res Opin. 2004 Jul;20(7):981-90. doi: 10.1185/030079904125003962.
- Background Naumann M, Albanese A, Heinen F, Molenaers G, Relja M. Safety and efficacy of botulinum toxin type A following long-term use. Eur J Neurol. 2006 Dec;13 Suppl 4:35-40. doi: 10.1111/j.1468-1331.2006.01652.x.
- Background Li M, Goldberger BA, Hopkins C. Fatal case of BOTOX-related anaphylaxis? J Forensic Sci. 2005 Jan;50(1):169-72.
- Background Forchheimer MB, Richards JS, Chiodo AE, Bryce TN, Dyson-Hudson TA. Cut point determination in the measurement of pain and its relationship to psychosocial and functional measures after traumatic spinal cord injury: a retrospective model spinal cord injury system analysis. Arch Phys Med Rehabil. 2011 Mar;92(3):419-24. doi: 10.1016/j.apmr.2010.08.029.
- Background Hanley MA, Jensen MP, Ehde DM, Robinson LR, Cardenas DD, Turner JA, Smith DG. Clinically significant change in pain intensity ratings in persons with spinal cord injury or amputation. Clin J Pain. 2006 Jan;22(1):25-31. doi: 10.1097/01.ajp.0000148628.69627.82.
- Background BEECHER HK. The powerful placebo. J Am Med Assoc. 1955 Dec 24;159(17):1602-6. doi: 10.1001/jama.1955.02960340022006. No abstract available.
- Background Widerstrom-Noga E, Biering-Sorensen F, Bryce T, Cardenas DD, Finnerup NB, Jensen MP, Richards JS, Siddall PJ. The international spinal cord injury pain basic data set. Spinal Cord. 2008 Dec;46(12):818-23. doi: 10.1038/sc.2008.64. Epub 2008 Jun 3.
- Background Jensen MP, Widerstrom-Noga E, Richards JS, Finnerup NB, Biering-Sorensen F, Cardenas DD. Reliability and validity of the International Spinal Cord Injury Basic Pain Data Set items as self-report measures. Spinal Cord. 2010 Mar;48(3):230-8. doi: 10.1038/sc.2009.112. Epub 2009 Sep 29.
- Background Ruta DA, Garratt AM, Leng M, Russell IT, MacDonald LM. A new approach to the measurement of quality of life. The Patient-Generated Index. Med Care. 1994 Nov;32(11):1109-26. doi: 10.1097/00005650-199411000-00004.
- Background Ruta DA, Garratt AM, Russell IT. Patient centred assessment of quality of life for patients with four common conditions. Qual Health Care. 1999 Mar;8(1):22-9. doi: 10.1136/qshc.8.1.22.
- Background Tugwell P, Bombardier C, Buchanan WW, Goldsmith CH, Grace E, Hanna B. The MACTAR Patient Preference Disability Questionnaire--an individualized functional priority approach for assessing improvement in physical disability in clinical trials in rheumatoid arthritis. J Rheumatol. 1987 Jun;14(3):446-51.
- Background Wright JG, Young NL. The patient-specific index: asking patients what they want. J Bone Joint Surg Am. 1997 Jul;79(7):974-83. doi: 10.2106/00004623-199707000-00003.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Botulinum toxin type A | Protein / enzyme biologic | 400 iu | Subcutaneous |