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

NCT04460521 | Recruiting Phase 4 FDA Drug

• 1 other identifier: ACTS Trial
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Carpal Tunnel Syndrome; Hand Injuries and Disorders; Nerve Compression; Splints; Carpal Tunnel; Carpal Tunnel Release

Keywords

Wrist splint; Carpal tunnel syndrome; Carpal tunnel release; Compression neuropathy; NAC; Conservative treatment; Hand surgery; Plastic surgery; N-acetylcysteine; Night splint

Outcome Measures

Primary Outcomes (1)

• 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.

  8 weeks

Secondary Outcomes (3)

• Number of participants who elect to have surgical carpal tunnel decompression after 8 weeks

  8 weeks

• Number of participants who elect to have surgical carpal tunnel decompression after 6 months

  6 months

• Change from baseline Boston Carpal Tunnel Questionnaire (BCTQ) at 6 months

  6 months

Study Arms (2)

NAC Group

EXPERIMENTAL

Participants in this group will given an N-acetylcysteine 500mg oral tablet daily in addition to wearing a standard carpal tunnel splint nightly (worn approximately 6-8 hours/day). Both interventions will take place concurrently for a total of 8 consecutive weeks.

Drug: N-Acetyl cysteine; Device: Wrist Splint

Placebo Group

PLACEBO COMPARATOR

Participants in this group will be given a placebo table to be taken orally daily in addition to wearing a standard carpal tunnel splint nightly (worn approximately 6-8 hours/day). Both interventions will take place concurrently for a total of 8 consecutive weeks.

Device: Wrist Splint

Interventions

N-Acetyl cysteine DRUG

In 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.

NAC Group

Wrist Splint DEVICE

Participants 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.

NAC Group; Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Any current medications which preclude use of NAC including antibiotics or nitroglycerin
• Breastfeeding patients or patients with nephrolithiasis
• Any history of proximal ipsilateral neck or proximal limb injury
• Secondary CTS related to pregnancy
• Unable for financial reasons to obtain a night splint (i.e. lack of insurance coverage or lack of financial means).

Sponsors & Collaborators

• Emily Krauss: lead

Study Sites (1)

Queen Elizabeth II Health Sciences Center, Halifax Infirmary Site

Halifax, Nova Scotia, B3H3A6, Canada

RECRUITING

Related Publications (11)

• 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.

  PMID: 10411196 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.

  PMID: 30343858 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.

  PMID: 8245050 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.

  PMID: 28367412 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.

  PMID: 25127999 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.

  PMID: 22786532 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.

  PMID: 25220611 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.

  PMID: 19559059 BACKGROUND

• Sud V, Freeland AE. Biochemistry of carpal tunnel syndrome. Microsurgery. 2005;25(1):44-6. doi: 10.1002/micr.20071.

  PMID: 15481038 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.

  PMID: 20872582 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.

  PMID: 2887090 BACKGROUND

MeSH Terms

Conditions

Carpal Tunnel Syndrome; Hand Injuries; Disease; Neuroma; Median Neuropathy; Tomaculous neuropathy

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Mononeuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Nerve Compression Syndromes; Cumulative Trauma Disorders; Sprains and Strains; Wounds and Injuries; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Michael Bezuhly, MD

  NSHA

  STUDY DIRECTOR

Central Study Contacts

Emily M Krauss, MD

CONTACT

902-473-7887; emilymkrauss@gmail.com

Anna Duncan, MD

CONTACT

anna.duncan@dal.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will undergo permutated block randomization to either the placebo controlled or experimental group in a 1:1 ratio. This method will be computer-generated. The allocation sequence will be concealed to research staff. The participants, clinic nurses, research assistants, and physician investigators as well as outcome assessors will be masked to participant group allocation. Unblinding will be permissible in extenuating circumstances only, such as if a participant experiences a severe adverse reaction secondary to the tablet and requires confirmation of the contents.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician

Model Details: Randomized, double-blind, placebo-controlled trial

Study Record Dates

• First Submitted: June 17, 2020
• First Posted: July 7, 2020
• Study Start: April 1, 2022
• Primary Completion: April 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: August 23, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)