Ignite Creation Date:
2024-05-06 @ 2:55 PM
Last Modification Date:
2024-10-26 @ 1:39 PM
Study NCT ID:
NCT04460521
Status:
RECRUITING
Last Update Posted:
2021-08-09
First Post:
2020-06-17
Brief Title:
The ACTS Trial N-acetylcysteine NAC and Night-splinting as a Non-operative Treatment for Carpal Tunnel Syndrome
Sponsor:
David Tang
Organization:
Nova Scotia Health Authority
Study Overview
Official Title:
The Use of N-acetylcysteine Supplementation in Addition to Night Splinting for Treatment of Mild to Moderate Carpal Tunnel Syndrome A Randomized Double-blind Placebo-controlled Trial
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ACTS
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 andor 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
Detailed Description:
Introduction Carpal tunnel syndrome CTS is the most prevalent and widely studied peripheral nerve entrapment syndrome with estimates between 10-20 of the general population having clinical symptoms of CTS at least once in their lifetime Classically it presents with symptoms of nocturnal numbness and tingling in the distribution of the median nerve often progressing to more constant parasthesias weakness and pain in the hand andor wrist and eventually thenar muscle atrophy There is a robust and continuously growing body of research available on the clinical presentation diagnosis and management of CTS Conservative non-operative management strategies including night splinting and corticosteroid injections have shown significant clinical benefit in improving the severity of CTS symptoms and preventing the need for carpal tunnel release CTR surgery However many patients with mild-moderate CTS will still go on to have CTR due to failure of conservative measures or lack of long-term efficacy N-acetylcysteine NAC is a safe and extremely well tolerated compound which acts as a powerful antioxidant and has been utilized in the treatment of many conditions including but not limited to acetaminophen toxicity various psychiatric disorders Alzheimers disease and polycystic ovarian syndrome Of note some studies using animal models have shown NAC to be effective in reducing oxidative stress and potentially expediting the recovery of peripheral nerve injuries This warrants consideration of the potential of NAC to impact peripheral nerve recovery in the non-operative treatment of mild to moderate carpal tunnel syndrome Given the safety of NAC and promising hypotheses to suggest neuroprotective and neuronal growth promoting effects on peripheral nerves The investigators propose the following project to examine whether supplementation with oral NAC in addition to standard night splinting significantly improves functional outcomes for mild to moderate CTS when compared to splinting alone
Methods This study will be a randomized double-blind parallel-group placebo-controlled human clinical trial Participants for this study will be recruited by staff residents and research assistants on a voluntary basis from both the outpatient Plastic Surgery clinic Plastic Surgery clinic waiting list and the Neurology clinic at the Queen Elizabeth II Health Sciences Center Halifax Infirmary in Nova Scotia Canada These will include patients both waiting for consultation with a hand surgeon for consideration of carpal tunnel release and patients who have already been assessed by a hand surgeon but have yet to undergo a trial of night splinting
For the purposes of this study a diagnosis of mild to moderate CTS will be primarily determined by clinical history of any intermittent or persistent numbness in the distribution of the median nerve andor pain in the hand or wrist Clinical exam findings consistent with a diagnosis of CTS will be determined by a CTS-6 score of 12 or higher indicating at least an 80 chance of a diagnosis of CTS
After identification of eligible participants they will be informed of the nature of the study and the proposed intervention and consented both verbally and in writing to participate in the study by a research assistant They will undergo permutated block randomization to either the placebo controlled or experimental group in a 11 ratio The participants and physiciansassessors will be masked to participant group allocation
Baseline variables will be collected from each participant including age gender smoking status previous diagnoses of carpal tunnel syndrome which side is affected or bilateral disease which side will undergo splinting as determined by severity previous treatments for carpal tunnel syndrome on both the study and non-study limb if bilateral disease clinical and electrodiagnostic severity of CTS duration of symptoms nature of onset any current pain medications for both CTS symptoms and non-CTS related pain employment status and comorbidities
Pre-treatment Evaluation Once the participants have given informed consent and been randomized they will be asked to complete a baseline Boston Carpal Tunnel Questionnaire BCTQ All patients will receive a prescription for a wrist splint and 8 weeks supply of either NAC tablets or a placebo
Post-treatment Evaluation Follow-up will take place at eight weeks by the surgeon to whom the patient was referred for consideration of carpal tunnel release Participants will be asked to complete another BCTQ to be compared to their baseline score At this time patients can decide if they wish to proceed with carpal tunnel release surgery or defer surgical treatment
For patients that do not decide to proceed with carpal tunnel release surgery a secondary outcome measure will include a follow up at 6 months at which time The investigators will collect patient reported outcomes including conversion to surgery continued use of conservative treatment modalities including night splinting or other treatment modalities and patient-reported outcomes in the way of a final BCTQ if surgery was not pursued
Outcome Measures The primary outcome measure in this study will be the overall score for symptom severity and hand function limitations as determined by the BCTQ at eight weeks post initiation of night splinting therapy A secondary outcome will be ratio of conversion to surgery versus continuation of conservative treatment or no treatment at all
Data Analysis For baseline demographic variables The investigators will use descriptive statistics means with standard deviations for continuous variables or frequency with percentages for categorical variables and assess between group similarities T-test and chi-square tests where appropriate will be used to determine significant differences in baseline demographics The primary between group analysis will be done with multiple linear regression with adjustments made for age at randomization gender symptom duration and baseline BCTQ score with an aim to identify significant differences in improvements in the BCTQ score between the treatment and control group at eight weeks and six months where applicable The investigators will also examine for significance in the ratio of conversion to surgery at eight weeks and six months Significance will be set as a p-value 005
Sample Size Based on the INSTINCTS trial by Chesterson and colleagues this study will require 240 total participants 120 per group The investigators will aim to detect a 15 or greater improvement in the BCTQ from assumed baseline value of 29 scale 1-5 SD 10 This would mean a 09 point 30 reduction in the NAC plus splinting group and a 045 point 15 reduction in the placebo plus splinting group with a pooled SD of 10 and mean difference of 045 Power will be set at 90 two-tailed significance at 5 and a 15 loss to follow up will be anticipated Recruitment of 120 participants for both the placebo-controlled and NAC groups will primarily be from the practice of a single hand surgeon DT and the practices of several local neurologists The primary hand surgeon DT has completed a preliminary audit of his practice and has determined that in the last year he completed 200 CTRs in the minor procedure clinic
Strengths and Limitations This study will have a robust sample size minimal potential for participant loss and strong clinical applications in the way of a minimally invasive adjunct to night splinting as a conservative treatment for mild to moderate carpal tunnel syndrome This study is limited in that the primary outcome measure is relatively subjective despite the fact that the BCTQ is a validated tool that has been applied clinically in reputable trials Additionally despite controlling for between group variability in baseline function severity of disease prior to treatment can certainly impact the degree of response to conservative measures and may confound results
Ethical Considerations Given that the participants in this study will have already decided to pursue investigations and treatment for their carpal tunnel syndrome prior to being informed of and consented for our trial there is a negligible ethical conflict of exposing a patient to tests and treatments that they would not have otherwise had Eligible participants will be given the standard information regarding the risks and benefits of both pursuing and delaying carpal tunnel release surgery and will not be delayed or denied surgery should they choose not to participate in the trial It is however acknowledged that there is a remote possibility of placing patients at risk by administering a medication NAC has been found to be a safe non-toxic substance with little-to-no reported short or long-term side effects Participants will be given as much information about the possible intervention as is needed and will be offered the right to withdraw from the study at any point in time without any repercussion to their medical care
Methods This study will be a randomized double-blind parallel-group placebo-controlled human clinical trial Participants for this study will be recruited by staff residents and research assistants on a voluntary basis from both the outpatient Plastic Surgery clinic Plastic Surgery clinic waiting list and the Neurology clinic at the Queen Elizabeth II Health Sciences Center Halifax Infirmary in Nova Scotia Canada These will include patients both waiting for consultation with a hand surgeon for consideration of carpal tunnel release and patients who have already been assessed by a hand surgeon but have yet to undergo a trial of night splinting
For the purposes of this study a diagnosis of mild to moderate CTS will be primarily determined by clinical history of any intermittent or persistent numbness in the distribution of the median nerve andor pain in the hand or wrist Clinical exam findings consistent with a diagnosis of CTS will be determined by a CTS-6 score of 12 or higher indicating at least an 80 chance of a diagnosis of CTS
After identification of eligible participants they will be informed of the nature of the study and the proposed intervention and consented both verbally and in writing to participate in the study by a research assistant They will undergo permutated block randomization to either the placebo controlled or experimental group in a 11 ratio The participants and physiciansassessors will be masked to participant group allocation
Baseline variables will be collected from each participant including age gender smoking status previous diagnoses of carpal tunnel syndrome which side is affected or bilateral disease which side will undergo splinting as determined by severity previous treatments for carpal tunnel syndrome on both the study and non-study limb if bilateral disease clinical and electrodiagnostic severity of CTS duration of symptoms nature of onset any current pain medications for both CTS symptoms and non-CTS related pain employment status and comorbidities
Pre-treatment Evaluation Once the participants have given informed consent and been randomized they will be asked to complete a baseline Boston Carpal Tunnel Questionnaire BCTQ All patients will receive a prescription for a wrist splint and 8 weeks supply of either NAC tablets or a placebo
Post-treatment Evaluation Follow-up will take place at eight weeks by the surgeon to whom the patient was referred for consideration of carpal tunnel release Participants will be asked to complete another BCTQ to be compared to their baseline score At this time patients can decide if they wish to proceed with carpal tunnel release surgery or defer surgical treatment
For patients that do not decide to proceed with carpal tunnel release surgery a secondary outcome measure will include a follow up at 6 months at which time The investigators will collect patient reported outcomes including conversion to surgery continued use of conservative treatment modalities including night splinting or other treatment modalities and patient-reported outcomes in the way of a final BCTQ if surgery was not pursued
Outcome Measures The primary outcome measure in this study will be the overall score for symptom severity and hand function limitations as determined by the BCTQ at eight weeks post initiation of night splinting therapy A secondary outcome will be ratio of conversion to surgery versus continuation of conservative treatment or no treatment at all
Data Analysis For baseline demographic variables The investigators will use descriptive statistics means with standard deviations for continuous variables or frequency with percentages for categorical variables and assess between group similarities T-test and chi-square tests where appropriate will be used to determine significant differences in baseline demographics The primary between group analysis will be done with multiple linear regression with adjustments made for age at randomization gender symptom duration and baseline BCTQ score with an aim to identify significant differences in improvements in the BCTQ score between the treatment and control group at eight weeks and six months where applicable The investigators will also examine for significance in the ratio of conversion to surgery at eight weeks and six months Significance will be set as a p-value 005
Sample Size Based on the INSTINCTS trial by Chesterson and colleagues this study will require 240 total participants 120 per group The investigators will aim to detect a 15 or greater improvement in the BCTQ from assumed baseline value of 29 scale 1-5 SD 10 This would mean a 09 point 30 reduction in the NAC plus splinting group and a 045 point 15 reduction in the placebo plus splinting group with a pooled SD of 10 and mean difference of 045 Power will be set at 90 two-tailed significance at 5 and a 15 loss to follow up will be anticipated Recruitment of 120 participants for both the placebo-controlled and NAC groups will primarily be from the practice of a single hand surgeon DT and the practices of several local neurologists The primary hand surgeon DT has completed a preliminary audit of his practice and has determined that in the last year he completed 200 CTRs in the minor procedure clinic
Strengths and Limitations This study will have a robust sample size minimal potential for participant loss and strong clinical applications in the way of a minimally invasive adjunct to night splinting as a conservative treatment for mild to moderate carpal tunnel syndrome This study is limited in that the primary outcome measure is relatively subjective despite the fact that the BCTQ is a validated tool that has been applied clinically in reputable trials Additionally despite controlling for between group variability in baseline function severity of disease prior to treatment can certainly impact the degree of response to conservative measures and may confound results
Ethical Considerations Given that the participants in this study will have already decided to pursue investigations and treatment for their carpal tunnel syndrome prior to being informed of and consented for our trial there is a negligible ethical conflict of exposing a patient to tests and treatments that they would not have otherwise had Eligible participants will be given the standard information regarding the risks and benefits of both pursuing and delaying carpal tunnel release surgery and will not be delayed or denied surgery should they choose not to participate in the trial It is however acknowledged that there is a remote possibility of placing patients at risk by administering a medication NAC has been found to be a safe non-toxic substance with little-to-no reported short or long-term side effects Participants will be given as much information about the possible intervention as is needed and will be offered the right to withdraw from the study at any point in time without any repercussion to their medical care
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None