NAC + Night Splints for Carpal Tunnel Syndrome

(ACTS Trial)

Overseen By Anna Duncan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Emily Krauss

Must not be taking: Antibiotics, Nitroglycerin

Disqualifiers: Previous surgery, Severe CTS, others

Stay on Your Current Meds You can continue your current medications while participating

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a daily oral supplement, N-acetylcysteine (NAC), can aid individuals with mild to moderate carpal tunnel syndrome (CTS), a condition causing numbness and pain in the hand. Participants will take either NAC or a placebo pill and wear a wrist splint at night for eight weeks. The main goal is to determine if NAC reduces symptoms and improves hand function more effectively than using the splint alone. Individuals with CTS symptoms for at least six weeks who have not received certain treatments may be suitable candidates. As a Phase 4 trial, this research aims to understand how the already FDA-approved NAC can benefit more patients with CTS.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking antibiotics or nitroglycerin, as these preclude the use of NAC.

What is the safety track record for these treatments?

Research has shown that N-acetylcysteine (NAC) is generally safe for people. It has treated various conditions, such as overdoses of paracetamol, a common pain reliever, and has a strong safety record. Most people tolerate NAC well, with only a few experiencing mild side effects like nausea or headaches. Serious side effects are rare.

Studies have found that NAC possesses anti-inflammatory properties, which might help with carpal tunnel syndrome (CTS). Researchers are testing it along with night splints to see if it can ease symptoms like pain and numbness in the hands. Overall, NAC is considered a safe option for most adults. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using N-acetylcysteine (NAC) for carpal tunnel syndrome because it offers a unique approach compared to the current standard treatments like wrist splints and corticosteroid injections. NAC is an antioxidant that may help reduce inflammation and oxidative stress in the carpal tunnel, which could alleviate symptoms more effectively. Unlike traditional treatments that primarily focus on physical support or reducing inflammation through steroids, NAC targets the biochemical environment, potentially providing a complementary benefit when combined with night splints. This novel mechanism of action is what makes NAC an exciting prospect in managing carpal tunnel syndrome.

What evidence suggests that NAC and night splints could be effective for carpal tunnel syndrome?

Research shows that wearing a night splint can significantly aid carpal tunnel syndrome (CTS) by improving nerve function and reducing symptoms. In this trial, participants in the NAC Group will receive N-acetylcysteine (NAC) along with a night splint. Studies suggest that NAC may aid CTS recovery by lowering oxidative stress. Known for its ability to reduce inflammation, NAC could also help alleviate CTS symptoms. While often used for various health issues and generally considered safe, its specific benefits for CTS remain under study. Combining NAC with a night splint might provide a non-surgical option to manage mild to moderate CTS symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Michael Bezuhly, MD

Principal Investigator

NSHA

Are You a Good Fit for This Trial?

This trial is for adults over 18 with mild to moderate Carpal Tunnel Syndrome (CTS) confirmed by clinical exam and nerve studies, who have had symptoms for at least 6 weeks. It's not for those who've tried splinting or steroid injections in the past 6 months, are on certain medications like antibiotics or nitroglycerin, have severe CTS, previous carpal surgery, pregnancy-related CTS, breastfeeding, kidney stones, financial barriers to getting a night splint or allergies to NAC.

Inclusion Criteria

I have had symptoms of carpal tunnel syndrome for at least 6 weeks.

I have been diagnosed with mild to moderate carpal tunnel syndrome in the last year.

Exclusion Criteria

I have not had night splinting or steroid injections in the affected limb in the last 6 months.

I am not on medications that interfere with NAC, like antibiotics or nitroglycerin.

You have carpal tunnel syndrome caused by pregnancy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either NAC or placebo tablets daily and wear a standard carpal tunnel splint nightly for 8 weeks

8 weeks

1 visit (in-person) for baseline assessment

Post-treatment Evaluation

Participants complete a follow-up BCTQ and decide on further treatment options

1 week

1 visit (in-person) for follow-up assessment

Follow-up

Participants are monitored for long-term outcomes and decide on surgical options if necessary

6 months

1 visit (in-person) at 6 months for final assessment

What Are the Treatments Tested in This Trial?

Interventions

• N-Acetyl cysteine
• Wrist Splint

Trial Overview The ACTS Trial is testing if taking an oral medication called N-acetylcysteine (NAC), known for its safety and anti-inflammatory properties can improve symptoms of CTS when used with night-splinting. Participants will either receive NAC or a placebo alongside standard night splinting for 8 weeks. The study aims to see if this combination reduces the need for surgery.

How Is the Trial Designed?

Group I: NAC Group Experimental Treatment 2 Interventions

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.

Group II: Placebo Group Placebo Group 1 Intervention

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.

Wrist Splint is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Wrist Splint for:

• Carpal Tunnel Syndrome
• Wrist Sprains
• Wrist Fractures

Approved in European Union as Wrist Orthosis for:

• Carpal Tunnel Syndrome
• Wrist Sprains
• Wrist Fractures
• Post-operative wrist stabilization

Approved in Canada as Night Splint for:

• Carpal Tunnel Syndrome
• Wrist Sprains
• Wrist Fractures

Who Is Running the Clinical Trial?

Emily Krauss

Lead Sponsor

Trials

1

Recruited

240+

David Tang

Lead Sponsor

Trials

1

Recruited

240+

Published Research Related to This Trial

Using a night orthosis for 6 weeks in patients with mild to moderate carpal tunnel syndrome (CTS) led to significant improvements in nerve conduction, including decreased motor distal latency and increased motor action potential by the 6th week.

While the electrophysiological improvements were notable, there were no significant changes in functional outcomes, suggesting that while the orthosis helps with nerve function, it may not directly translate to improved daily activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of orthotic intervention on nerve conduction and functional outcome in carpal tunnel syndrome: A prospective follow-up study. Celik, B., Paker, N., Celik, EC., et al.[2015]

N-acetylcysteine (NAC) was successfully used to treat a 40-year-old woman who suffered liquid nitrogen (LN2) injuries, alongside antibiotics and wound care.

Six months after the injury, the patient regained full range of motion, sensation, and function in her hands, indicating that NAC may be an effective treatment option for LN2 burns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of N-acetylcysteine in the Treatment of Accidental Submersion of the Hands in Liquid Nitrogen. Orozco, E., Birnbrich, A., Liberman, SR.[2021]

In a rat model of acute spinal cord injury, combining early decompression surgery with N-Acetylcysteine (NAC) significantly improved neurological outcomes compared to surgery alone, as indicated by higher Basso, Beattie, and Bresnahan scores.

The study suggests that NAC enhances the neuroprotective effects of early decompression surgery by reducing inflammation and apoptosis, making it a promising treatment strategy for acute spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-Acetylcysteine alleviates spinal cord injury in rats after early decompression surgery by regulating inflammation and apoptosis. Guo, X., He, J., Zhang, R., et al.[2022]

N-Acetylcysteine (NAC) effectively prevents sensory neuronal loss after peripheral nerve transection in a dose-dependent manner, with significant protection observed at doses of 10 mg/kg/day and above.

The study, using a rat model, indicates that higher doses (150 and 300 mg/kg/day) completely prevent neuronal loss, suggesting NAC has a wide therapeutic range and potential for clinical use in nerve injury recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the dose-response of N-acetylcysteine in the prevention of sensory neuronal loss after peripheral nerve injury. West, CA., Hart, AM., Terenghi, G., et al.[2019]

In a study of 20 patients with obstructive sleep apnoea syndrome (OSAS), those treated with N-acetylcysteine (NAC) showed significant improvements in sleep quality, including increased slow wave sleep and sleep efficiency, as well as reductions in apnoea-hypopnoea index and oxygen desaturation events after 30 days of treatment.

NAC also decreased markers of oxidative stress, suggesting it may help improve OSAS symptoms and potentially reduce reliance on continuous positive airway pressure therapy in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-oxidant treatment in obstructive sleep apnoea syndrome. Sadasivam, K., Patial, K., Vijayan, VK., et al.[2011]

Night-only splint therapy for carpal tunnel syndrome (CTS) showed significant long-term efficacy, with improvements in symptoms and nerve function observed at both three and six months in a study of 50 patients.

The therapy led to notable enhancements in symptom scores, functional scores, and nerve conduction velocities, indicating that this non-invasive treatment can effectively alleviate CTS symptoms over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neutral wrist splinting in carpal tunnel syndrome: a 3- and 6-months clinical and neurophysiologic follow-up evaluation of night-only splint therapy. Premoselli, S., Sioli, P., Grossi, A., et al.[2015]

Night splinting significantly improved insomnia symptoms in patients with carpal tunnel syndrome compared to no splinting, indicating it can be an effective non-surgical treatment option.

Surgery provided greater improvement in insomnia symptoms than splinting, although both treatments showed similar sleep quality outcomes according to subjective measures, suggesting that while splinting helps, surgery may be more effective for severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of splinting and surgery on sleep disturbance in carpal tunnel syndrome. Rubin, G., Orbach, H., Rinott, M., et al.[2019]

In a randomized clinical trial involving 21 patients with carpal tunnel syndrome (CTS), those who wore wrist splints full-time showed greater improvements in both sensory and motor nerve function compared to those who wore splints only at night.

Overall, the study found that splinting significantly reduced symptoms and functional deficits in CTS, with full-time wear leading to better physiological outcomes, highlighting the importance of adherence to treatment instructions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neutral wrist splinting in carpal tunnel syndrome: a comparison of night-only versus full-time wear instructions. Walker, WC., Metzler, M., Cifu, DX., et al.[2022]

Nocturnal wrist splinting is an effective treatment for carpal tunnel syndrome, as it helps reduce elevated pressures in the carpal tunnel during sleep.

The study assessed four commonly used prefabricated orthoses, providing insights into their design and effectiveness in maintaining optimal wrist and finger positioning to alleviate symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of range-of-motion constraints provided by prefabricated splints used in the treatment of carpal tunnel syndrome: a pilot study. Apfel, E., Johnson, M., Abrams, R.[2019]

Pre-incisional treatment with N-acetylcysteine (NAC) in a rat model showed potential benefits in wound healing, particularly at a concentration of 0.03%, which resulted in smaller and narrower scars at early healing stages.

While NAC treatment decreased wound size and width, the most significant improvements were observed at 0.03% concentration, indicating a possible optimal dosage for enhancing early scar formation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-Acetylcysteine Added to Local Anesthesia Reduces Scar Area and Width in Early Wound Healing-An Animal Model Study. Paskal, W., Paskal, AM., Pietruski, P., et al.[2021]

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04460521/the-acts-trial-n-acetylcysteine-nac-and-night-splinting-as-a-non-operative-treatment-for-carpal-tunnel-syndrome

The ACTS Trial: N-acetylcysteine (NAC) and Night- ... Of note, some studies using animal models have shown NAC to be effective in reducing oxidative stress and potentially expediting the recovery of ...

2. withpower.com withpower.com/trial/phase-4-carpal-tunnel-syndrome-7-2021-27e6d

NAC + Night Splints for Carpal Tunnel Syndrome Using a night orthosis for 6 weeks in patients with mild to moderate carpal tunnel syndrome (CTS) led to significant improvements in nerve conduction, including ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5747578/

l-Acetyl-carnitine in Patients with Carpal Tunnel Syndrome LAC reduced pain in patients with mild and moderate CTS, a result that is possibly due to both its neuroprotective action and its central anti-nociceptive ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8234027/

N-Acetylcysteine (NAC): Impacts on Human Health - PMC Thus, current data reveal that NAC in patients after cardiothoracic surgery is effective in preventing arrhythmias, requiring further randomized clinical ...

5. scirp.org scirp.org/journal/paperinformation?paperid=115091

Improvement in Early Recovery after Endoscopic Carpal ... This study demonstrated that patients who took the nerve support supplement NeuroGen had a significant improvement in reducing symptoms and improving function ...

6. webmd.com webmd.com/vitamins/ai/ingredientmono-1018/n-acetyl-cysteine-nac

N-Acetyl Cysteine (Nac) – Uses, Side Effects, and More When taken by mouth: N-acetyl cysteine is likely safe for most adults. N-acetyl cysteine is an FDA-approved prescription drug. It can cause side effects such as ...