The ACTS Trial: N-acetylcysteine (NAC) and Night-splinting as a Non-operative Treatment for Carpal Tunnel Syndrome

Summary

Carpal tunnel syndrome (CTS) is the most common nerve compression syndrome worldwide, causing significant chronic pain, functional impairment, and lowered quality of life for individuals of various backgrounds. CTS is caused by chronic compression of the median nerve in the carpal tunnel of the wrist, causing numbness and pain in the palm, thumb, index, and middle fingers and eventual weakness of the hand. Many different treatments for CTS have been proposed and studied, including but not limited to non-operative treatments such as wrist splinting, steroid injections, and lifestyle modifications as well as operative treatments, such as surgical carpal tunnel release (CTR). To date, very few oral medications have been shown to be effective as conservative treatments for CTS. In this study the investigators will examine whether there is any benefit to using oral N-acetylcysteine (NAC) as an adjunctive treatment for mild to moderate CTS in addition to a standard 8-week trial of night splinting. NAC has been used in humans for various purposes, is extremely safe and has very few side effects, and has been shown to have anti-inflammation properties which may help treat CTS. The investigators will study this by performing a randomized controlled trial, comparing patients receiving oral NAC and standard night splinting to patients receiving an identical placebo and standard night splinting. Both patient groups will be assessed using a questionnaire to assess for severity of their CTS symptoms both before and after the 8-week treatment. The primary objective will be to determine whether supplementation with oral NAC in addition to night splinting has any significant impact on patient-reported symptoms and functional impairment when compared to night splinting alone. The investigators will also measure secondary outcomes including whether patients decide to have surgery for their CTS after treatment and/or continued use of other treatments. This study has the potential to have a significant positive impact on patients by identifying a safe, inexpensive, accessible, and well tolerated conservative treatment for mild to moderate carpal tunnel syndrome, and potentially preventing the need for additional, more invasive treatments such as surgery.

Timeline

Start

2022-04-01

Primary completion

2026-04-01

Completion

2026-10-01

Publications

• Background Atroshi I, Gummesson C, Johnsson R, Ornstein E, Ranstam J, Rosen I. Prevalence of carpal tunnel syndrome in a general population. JAMA. 1999 Jul 14;282(2):153-8. doi: 10.1001/jama.282.2.153.
• Background Chesterton LS, Blagojevic-Bucknall M, Burton C, Dziedzic KS, Davenport G, Jowett SM, Myers HL, Oppong R, Rathod-Mistry T, van der Windt DA, Hay EM, Roddy E. The clinical and cost-effectiveness of corticosteroid injection versus night splints for carpal tunnel syndrome (INSTINCTS trial): an open-label, parallel group, randomised controlled trial. Lancet. 2018 Oct 20;392(10156):1423-1433. doi: 10.1016/S0140-6736(18)31572-1.
• Background Levine DW, Simmons BP, Koris MJ, Daltroy LH, Hohl GG, Fossel AH, Katz JN. A self-administered questionnaire for the assessment of severity of symptoms and functional status in carpal tunnel syndrome. J Bone Joint Surg Am. 1993 Nov;75(11):1585-92. doi: 10.2106/00004623-199311000-00002.
• Background Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A. A Review on Various Uses of N-Acetyl Cysteine. Cell J. 2017 Apr-Jun;19(1):11-17. doi: 10.22074/cellj.2016.4872. Epub 2016 Dec 21.
• Background Huisstede BM, Friden J, Coert JH, Hoogvliet P; European HANDGUIDE Group. Carpal tunnel syndrome: hand surgeons, hand therapists, and physical medicine and rehabilitation physicians agree on a multidisciplinary treatment guideline-results from the European HANDGUIDE Study. Arch Phys Med Rehabil. 2014 Dec;95(12):2253-63. doi: 10.1016/j.apmr.2014.06.022. Epub 2014 Aug 12.
• Background Page MJ, Massy-Westropp N, O'Connor D, Pitt V. Splinting for carpal tunnel syndrome. Cochrane Database Syst Rev. 2012 Jul 11;2012(7):CD010003. doi: 10.1002/14651858.CD010003.
• Background Chan KM, Gordon T, Zochodne DW, Power HA. Improving peripheral nerve regeneration: from molecular mechanisms to potential therapeutic targets. Exp Neurol. 2014 Nov;261:826-35. doi: 10.1016/j.expneurol.2014.09.006. Epub 2014 Sep 16.
• Background Reid AJ, Shawcross SG, Hamilton AE, Wiberg M, Terenghi G. N-acetylcysteine alters apoptotic gene expression in axotomised primary sensory afferent subpopulations. Neurosci Res. 2009 Oct;65(2):148-55. doi: 10.1016/j.neures.2009.06.008. Epub 2009 Jun 24.
• Background Sud V, Freeland AE. Biochemistry of carpal tunnel syndrome. Microsurgery. 2005;25(1):44-6. doi: 10.1002/micr.20071.
• Background Kim JK, Koh YD, Kim JS, Hann HJ, Kim MJ. Oxidative stress in subsynovial connective tissue of idiopathic carpal tunnel syndrome. J Orthop Res. 2010 Nov;28(11):1463-8. doi: 10.1002/jor.21163.
• Background Lingjaerde O, Ahlfors UG, Bech P, Dencker SJ, Elgen K. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand Suppl. 1987;334:1-100. doi: 10.1111/j.1600-0447.1987.tb10566.x. No abstract available.

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