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.
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
Symptoms of CTS must have been present for ≥ 6 weeks
The patient must be ≥ 18 years of age.
Any previous carpal tunnel release procedure on the ipsilateral limb
Any previous corticosteroid injection in the last 6 months on the ipsilateral limb
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
Any known or suspected allergy to NAC
Parallel
N-Acetyl cysteine
DrugIn addition to splinting, both groups will receive an oral tablet to take daily for 8 weeks. Participants assigned to the experimental group will receive oral NAC (500 mg PO daily for eight weeks; based on recommended daily dose for use as an antioxidant and dosing in previous human clinical trials and animal studies), and those assigned to the control group will be given a similar looking placebo with identical instructions. Tablets will be provided in a blister pack to assist with compliance.
Wrist Splint
DeviceParticipants in both arms will be given a standard prescription for a prefabricated night splint which keeps the wrist in a neutral position and instructed on proper use and the importance of consistent use. To limit splint variability, we will ensure that splint prescriptions are written such that a MedSpec Wrist Lacer II splint is obtained from the patient's pharmacy. This is the most commonly available brand locally and meets the criteria for wrist, metacarpophalangeal, and interphalangeal joint positioning. They will be advised to wear the splint consistently during sleeping hours on their affected wrist for eight weeks, as is the standard of practice.
Change from baseline Boston Carpal Tunnel Questionnaire (BCTQ) at 8 weeks
The Boston Carpal Tunnel Questionnaire (BCTQ) is a validated tool for patient-reported outcomes with respect to symptoms and functional impact of carpal tunnel syndrome. It consists of both a symptom severity scale (SSS) (11 items) and functional status scale (FSS) (8 items). Each item on both of these scales is scored on a 5-point rating system, with higher numbers indicating more severe symptoms and higher functional disability. The possible range of both the FSS and SSS combined is from 19-95. A baseline BCTQ will be administered at the first visit, which will be used to calculate the overall change in BCTQ score at 8 weeks.
Number of participants who elect to have surgical carpal tunnel decompression after 8 weeks
The participant's decision to continue with conservative treatment or to elect to have a carpal tunnel release procedure at 8-weeks post-treatment will be a secondary outcome measure.
Number of participants who elect to have surgical carpal tunnel decompression after 6 months
If at 8-weeks, the participant decides not to have carpal tunnel release surgery, an additional follow up visit will be scheduled at 6 months time. At this point in time, the participants decision to have carpal tunnel release surgery or to continue to conservative modalities will be a subgroup analysis.
Change from baseline Boston Carpal Tunnel Questionnaire (BCTQ) at 6 months
If the participant decides not have have a carpal tunnel release at 8 weeks, an additional follow up visit will be scheduled in 6 months. At this time, a third BCTQ will be completed to assess change in long-term BCTQ compared to baseline.
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Emily Krauss
Lead sponsor
Nova Scotia Health Authority
Sponsor institution
