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

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.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. The patient has a confirmed diagnosis of mild to moderate idiopathic unilateral or bilateral CTS as determined by both clinical exam findings and electrodiagnostic nerve conduction studies (median nerve distal motor latency ≥ 4.3 milliseconds and/or median nerve sensory distal latency ≥ 3.5 milliseconds at the wrist) performed within the preceding year prior to enrollment
2. Symptoms of CTS must have been present for ≥ 6 weeks
3. The patient must be ≥ 18 years of age.

Exclusion Criteria:

1. Any previous carpal tunnel release procedure on the ipsilateral limb
2. Any previous corticosteroid injection in the last 6 months on the ipsilateral limb
3. Severe CTS/signs of median nerve denervation with axonal loss determined by constant wrist or hand pain, constant parasthesias in the median nerve distribution, or thenar muscle atrophy in the ipsilateral limb
4. Any known or suspected allergy to NAC
5. Any current medications which preclude use of NAC including antibiotics or nitroglycerin
6. Breastfeeding patients or patients with nephrolithiasis
7. Any history of proximal ipsilateral neck or proximal limb injury
8. Secondary CTS related to pregnancy
9. Unable for financial reasons to obtain a night splint (i.e. lack of insurance coverage or lack of financial means).

• BACKGROUNDAtroshi 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. PMID 10411196
• BACKGROUNDChesterton 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. PMID 30343858
• BACKGROUNDLevine 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. PMID 8245050
• BACKGROUNDMokhtari 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. PMID 28367412
• BACKGROUNDHuisstede 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. PMID 25127999
• BACKGROUNDPage 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. PMID 22786532
• BACKGROUNDChan 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.