Noninvasive Brain Stimulation for Carpal Tunnel Syndrome

Overseen By Felipe Fregni, MD PhD mph

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Spaulding Rehabilitation Hospital

Must not be taking: Carbamazepine

Disqualifiers: Pregnancy, Major depression, Neurological disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 9 weeks

95 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to treat pain in people with Carpal Tunnel Syndrome using a combination of noninvasive brain treatments: Transcranial Direct Current Stimulation (tDCS, a mild electrical current applied to the head) and Transcranial Ultrasound (TUS, sound waves). The goal is to determine if these methods can reduce pain compared to a placebo. Individuals who have experienced Carpal Tunnel pain for at least six months and find little relief from typical treatments might be suitable candidates. Participants will receive either the active treatment or a sham (inactive) version for comparison. As an unphased trial, this study provides a unique opportunity to explore innovative treatments that might offer relief when standard options have failed.

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 have used carbamazepine in the past 6 months.

What prior data suggests that this noninvasive brain stimulation is safe for treating Carpal Tunnel Syndrome?

Research shows that Transcranial Direct Current Stimulation (tDCS) is generally safe. Studies indicate that using tDCS at levels of 4 mA or less does not cause serious problems, meaning most people tolerate it well.

For Transcranial Ultrasound (TUS), evidence suggests it is also safe when used correctly. Reports indicate that TUS rarely causes negative effects, with fewer than 10% of people experiencing any issues, similar to other brain stimulation methods.

Both treatments have been used in other studies without major safety concerns, suggesting they are likely safe for this clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for carpal tunnel syndrome because they offer a noninvasive approach that could potentially reduce symptoms without the need for surgery or medication. Transcranial Direct Current Stimulation (tDCS) and Transcranial Ultrasound (TUS) work by gently stimulating specific brain regions, which could help alleviate pain and improve nerve function. Unlike standard treatments like wrist splints or corticosteroid injections, these methods aim to target the neurological pathways involved in carpal tunnel syndrome directly. This innovative technique could provide quicker relief and long-lasting benefits, making it a promising option for patients seeking alternatives to conventional therapies.

What evidence suggests that this trial's treatments could be effective for Carpal Tunnel Syndrome?

Research has shown that Transcranial Direct Current Stimulation (tDCS) can reduce hand pain and improve well-being in people with carpal tunnel syndrome. Some patients reported feeling happier and experiencing less pain after these treatments. Similarly, studies indicate that Transcranial Ultrasound (TUS) can also alleviate pain and enhance hand function in carpal tunnel syndrome. It works by affecting brain cell communication, which can lessen pain. This trial explores whether using tDCS and TUS together in the active treatment arm can effectively lower pain levels for those with carpal tunnel syndrome. ^{3 4 5 6 7}

Who Is on the Research Team?

Felipe Fregni, MD, PhD, MPH

Principal Investigator

Spaulding Rehabilitation Network

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with Carpal Tunnel Syndrome causing chronic pain despite previous treatments. Participants must have had pain for at least 6 months, feel it on most days, and rate it at least a 3 out of 10. They can't join if they're pregnant, have used certain medications recently, suffer from major depression or neurological issues like stroke or epilepsy, have metal implants in the brain, or a history of substance abuse.

Inclusion Criteria

Able to provide informed consent to participate in the study

I have chronic wrist pain from CTS, spreading beyond the usual areas, for over 6 months.

My chronic pain persists despite first-line treatments.

Exclusion Criteria

I have not taken carbamazepine in the last 6 months.

Subject is pregnant

I do not have any metal implants in my head.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 20 minutes of active or sham transcranial direct current stimulation (tDCS) and transcranial ultrasound (TUS) for the treatment of pain in Carpal Tunnel Syndrome

9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Direct Current Stimulation (tDCS)
• Transcranial Ultrasound (TUS)

Trial Overview The study tests whether transcranial Direct Current Stimulation (tDCS) combined with Transcranial Ultrasound (TUS) can reduce pain in Carpal Tunnel Syndrome patients better than sham (fake) stimulation. The hypothesis is that active stimulation will lower pain levels more effectively.

How Is the Trial Designed?

Group I: Active tDCS + Active TUS Experimental Treatment 2 Interventions

Subjects in the experimental group will undergo 20 minutes of active transcranial direct current stimulation (tDCS) and active transcranial ultrasound (TUS).

Group II: Sham tDCS + Sham TUS Placebo Group 2 Interventions

Subjects in the sham group will undergo 20 minutes of sham transcranial direct current stimulation (tDCS) and sham transcranial ultrasound (TUS).

Transcranial Direct Current Stimulation (tDCS) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Direct Current Stimulation for:

• Depression
• Stroke rehabilitation
• Chronic pain management
• Research use for various neurological and psychiatric conditions including autism spectrum disorder

Approved in European Union as Transcranial Direct Current Stimulation for:

• Depression
• Stroke rehabilitation
• Chronic pain management
• Research use for various neurological and psychiatric conditions including autism spectrum disorder

Approved in Canada as Transcranial Direct Current Stimulation for:

• Depression
• Stroke rehabilitation
• Chronic pain management
• Research use for various neurological and psychiatric conditions including autism spectrum disorder

Who Is Running the Clinical Trial?

Spaulding Rehabilitation Hospital

Lead Sponsor

Trials

143

Recruited

11,200+

Highland Instruments, Inc.

Industry Sponsor

Trials

11

Recruited

650+

Published Research Related to This Trial

High Definition transcranial direct current stimulation (HD-tDCS) is safe and well-tolerated in older adults, with no serious adverse events reported during a study involving 101 participants at stimulation intensities of 2 mA and 3 mA.

The study demonstrated effective blinding, as participants could not accurately distinguish between active and sham stimulation, indicating that HD-tDCS can be reliably used in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. Reckow, J., Rahman-Filipiak, A., Garcia, S., et al.[2020]

In a randomized controlled trial involving 40 patients with mild to moderate carpal tunnel syndrome, both real and sham therapeutic ultrasound treatments resulted in significant improvements in symptoms and nerve function over 1 year, but there were no significant differences between the two groups.

The study concluded that therapeutic ultrasound does not provide a clinically significant benefit for treating carpal tunnel syndrome, with improvements likely due to other factors such as initial symptom severity and additional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound therapy adds no benefit to splinting in carpal tunnel syndrome. Jothi, KP., Bland, JDP.[2020]

In a study of 26 chronic stroke patients, combining anodal transcranial direct current stimulation (tDCS) with occupational therapy significantly improved fine motor skills, as measured by the modified Jebsen-Taylor Hand Function Test, compared to a sham stimulation group.

The benefits of the tDCS intervention were evident immediately after treatment and persisted up to 40 days later, although there was no observed impact on handgrip strength or upper limb function scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of anodal tDCS and occupational therapy on fine motor skill deficits in patients with chronic stroke. Ilić, NV., Dubljanin-Raspopović, E., Nedeljković, U., et al.[2018]

A systematic review of nine studies involving 371 stroke patients found that transcranial direct current stimulation (tDCS) combined with rehabilitation showed a small non-significant effect on upper extremity recovery, with effect sizes of +0.11 for impairments and +0.24 for activities.

The variability in tDCS methodologies and rehabilitation programs suggests that while there may be some benefit, the current evidence is not strong enough to confirm its efficacy, indicating a need for further research to identify which patients may benefit most from specific tDCS treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple sessions of transcranial direct current stimulation and upper extremity rehabilitation in stroke: A review and meta-analysis. Tedesco Triccas, L., Burridge, JH., Hughes, AM., et al.[2022]

Transcranial direct current stimulation (tDCS) has been found to be safe for use in humans, with no severe complications reported in studies involving both adults and children when applied at intensities of 4 mA or less for up to 60 minutes.

Animal studies indicate that the electrical current used in tDCS is significantly lower than the threshold that could cause permanent changes to brain tissue, suggesting a strong safety profile for this neurorehabilitation method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation in Neurorehabilitation. Ko, MH.[2023]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

Optimized high-definition montages for transcranial direct current stimulation (tDCS) can increase stimulation intensity by an average of 0.3 V/m compared to unoptimized montages, which is crucial for targeting areas beneath skull defects.

Large skull defects with titanium or acrylic plates can reduce stimulation intensity by about 80%, while smaller defects filled with cerebrospinal fluid or scar tissue can increase stimulation intensity by about 200%, highlighting the importance of individual anatomical considerations in tDCS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimized high-definition tDCS in patients with skull defects and skull plates. Guillen, A., Truong, DQ., Datta, A., et al.[2023]

In a study of 36 hands from 31 patients with carpal tunnel syndrome (CTS) who had previously failed standard treatments, a combination of low-level laser acupuncture and microamps TENS significantly reduced pain, with 91.6% of hands experiencing no pain or over 50% pain reduction after treatment.

The treatment was not only effective but also cost-efficient, costing around $1,000 compared to the estimated $12,000 for standard care, and it was deemed safe when performed by a licensed acupuncturist, with minimal recurrence of pain in follow-ups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carpal tunnel syndrome: clinical outcome after low-level laser acupuncture, microamps transcutaneous electrical nerve stimulation, and other alternative therapies--an open protocol study. Branco, K., Naeser, MA.[2004]

Neurodynamic mobilisation techniques (NMTs) significantly reduced pain intensity in women with mild or moderate carpal tunnel syndrome (CTS), showing a decrease of 1.15 points at 5 weeks and 2 points at 10 weeks compared to the control group.

NMTs also improved functional status more effectively than placebo treatments, with a difference of 0.45 at 5 weeks and 0.84 at 10 weeks, suggesting that NMTs can be a beneficial conservative treatment option for CTS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of the median nerve neurodynamic mobilisation techniques in women with mild or moderate bilateral carpal tunnel syndrome: A single-blind clinical randomised trial. Beddaa, H., Kably, B., Marzouk, B., et al.[2022]

A systematic review of 12 studies involving 869 participants found that acupuncture and laser acupuncture may have little to no significant effect on the symptoms of carpal tunnel syndrome (CTS) compared to placebo or sham treatments, indicating uncertainty about their efficacy.

While acupuncture was associated with minimal adverse events, such as local pain and bruising, no serious adverse events were reported, suggesting it is a relatively safe option, though high-quality trials are needed to confirm its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acupuncture and related interventions for the treatment of symptoms associated with carpal tunnel syndrome. Choi, GH., Wieland, LS., Lee, H., et al.[2022]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

Intramuscular stimulation (IMS) of the pronator teres muscle significantly improved clinical parameters in patients with carpal tunnel syndrome (CTS), showing better results than the control group receiving acupuncture.

Both IMS and acupuncture groups experienced a reduction in the diameter of the median nerve, but IMS demonstrated greater overall clinical improvement, suggesting it may be a low-risk alternative treatment while awaiting surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment effect of intramuscular stimulation on carpal tunnel syndrome: A blinded randomized trial on 75 patients. Kvist, KB., Hilland, R., Enehaug, R., et al.[2021]

Microdermabrasion significantly reduced skin resistance by about 32%, allowing for higher doses of transcranial direct current stimulation (tDCS) without increasing skin sensations or device limitations.

The study found that while microdermabrasion increased perceived sensations slightly when not combined with sonication, overall, it enabled safer and more effective delivery of tDCS by lowering the voltage needed to achieve the same current.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. Chhatbar, PY., Liu, S., Ramakrishnan, V., et al.[2023]

High-frequency repeated transcranial magnetic stimulation (HF-rTMS) significantly improves global cognitive function in stroke patients compared to sham stimulation, with a large effect size (SMD = 1.95).

Dual transcranial direct current stimulation (dual-tDCS) shows a significant improvement in memory performance compared to sham stimulation, indicating its potential benefit for post-stroke memory impairment. Both NIBS methods are considered safe with no significant safety differences noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of different noninvasive brain stimulation therapies for recovery of global cognitive function, attention, memory, and executive function after stroke: a network meta-analysis of randomized controlled trials. Wang, Y., Liu, W., Chen, J., et al.[2023]

In a study of 32 stroke inpatients, those who received bihemispheric transcranial direct current stimulation (tDCS) alongside physical and occupational therapy showed significantly greater improvements in upper extremity motor function compared to those who received sham tDCS.

The most notable benefits were observed in chronic stroke patients (over 6 months post-stroke), indicating that tDCS may be particularly effective for this group in enhancing their functional independence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Bihemispheric Transcranial Direct Current Stimulation on Upper Extremity Function in Stroke Patients: A randomized Double-Blind Sham-Controlled Study. Alisar, DC., Ozen, S., Sozay, S.[2020]

Citations

1. withpower.com withpower.com/trial/phase-3d9a9

Noninvasive Brain Stimulation for Carpal Tunnel Syndrome The purpose of this study is to assess the effects of tDCS in combination with TUS for the treatment of pain in subjects with Carpal Tunnel Syndrome.

2. gpsych.bmj.com gpsych.bmj.com/content/38/3/e102077

Short-term effects of transcranial direct current stimulation ... The study found no significant change in pain sensitivity, but observed a significant reduction in rumination at 1-week and 2-week follow-ups.

3. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2017.00508/full

Cathodal Transcranial Direct Current Stimulation Improves ... Both patients reported a sensation of general wellness, of happiness, of reduction of hand pain and an improvement of rest particularly after C- ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04206215

Noninvasive Brain Stimulation for Treating Carpal Tunnel ... The purpose of this study is to assess the effects of tDCS in combination with TUS for the treatment of pain in subjects with Carpal Tunnel Syndrome.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10525175/

Efficiency of Direct Transcutaneous Electroneurostimulation of ... Results: Our research showed that TENS significantly decreased the pain syndrome, sensory disorders, and motor deficits in the patients after CTDS.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04206215

Noninvasive Brain Stimulation for Treating Carpal Tunnel ... The investigators will measure safety of tDCS and TUS by measuring changes in the Visual Analog Mood Scale. This scale will range from zero (low or worst mood) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5007190/

Safety of transcranial Direct Current Stimulation: Evidence ... This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and ...