Remote tDCS + Somatosensory Training for Phantom Limb Pain

(PLP-EVEREST Trial)

Overseen By Kevin Pacheco-Barrios, MS, MSc, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Spaulding Rehabilitation Hospital

Disqualifiers: Unstable medical, Psychiatric, Substance abuse, others

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

Compensation: Varies

Number of Visits: 23

Duration: 4 weeks

290 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new home-based treatment for phantom limb pain (PLP), which is pain felt in an amputated limb. Researchers compare two approaches: one group uses a portable device for brain stimulation (M1 anodal home-based tDCS, a type of transcranial direct current stimulation) with somatosensory training, while the other group continues with usual care, such as medication and physical therapy. The goal is to determine if the new combined treatment reduces pain more effectively. Individuals who have had a limb amputation and experience PLP at least once a week may be suitable for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative treatments for PLP in a flexible research setting.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial allows participants to continue their usual care, including current medications, physical therapy, and occupational therapy.

What prior data suggests that this device is safe for home-based use?

Research has shown that using transcranial direct current stimulation (tDCS) at home is generally safe for people with phantom limb pain. Previous studies used this treatment without causing harmful effects. It works by sending a small, gentle electrical current through the scalp to the brain, and patients usually tolerate it well.

Studies have also found that somatosensory training, which includes exercises involving the senses, can safely help reduce phantom limb pain. Participants in these studies did not report any major negative effects.

Both treatments in this trial have been tested in similar situations without serious safety issues. This suggests they are likely safe, but discussing any concerns with the trial team or a healthcare professional is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using M1 anodal home-based transcranial direct current stimulation (tDCS) combined with somatosensory training for phantom limb pain because it offers a non-invasive, at-home approach to pain management. Unlike traditional treatments that often rely on medications, physical therapy, or behavioral therapy, this method uses low-level electrical currents applied directly to the scalp, which can modulate brain activity to alleviate pain. This innovative approach not only provides a new mechanism of action by directly targeting brain activity but also empowers patients to manage their treatment conveniently at home, potentially enhancing adherence and outcomes.

What evidence suggests that this trial's treatments could be effective for phantom limb pain?

Research has shown that transcranial direct current stimulation (tDCS) can provide lasting relief from phantom limb pain (PLP). One study found that individuals who had lost a limb experienced significant pain relief after receiving tDCS on the brain's motor area for five days. Additionally, somatosensory training reduced PLP by 32.1% six weeks after the training, with participants reporting less pain by the end of each training day. In this trial, one group of participants will receive M1 anodal home-based tDCS combined with somatosensory training, which may effectively reduce PLP. Another group will continue with their usual care, including pharmacological treatments, physical therapy, occupational therapy, and/or behavioral therapy. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with limb amputations who regularly experience phantom limb pain (PLP) at least once a week, and have chronic pain rated at least 4 on the numeric rating scale. It's not suitable for those with significant medical or psychiatric disorders, recent substance abuse, uncompensated psychiatric conditions, major neurological history or neurosurgery affecting tDCS distribution, or implanted brain devices.

Inclusion Criteria

I am older than 18 years.

I experience chronic pain with an average intensity of at least 4 out of 10.

I have had a limb amputated.

Exclusion Criteria

You have a mental health condition that is not being managed or treated.

I do not have any serious or unstable health or mental conditions.

I've had brain surgery that could affect electrical therapy on 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 daily sessions of active anodal M1 home-based tDCS combined with somatosensory training or usual care

4 weeks

20 visits (home-based)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• M1 anodal home-based tDCS
• Somatosensory Training

Trial Overview The study tests home-based transcranial direct current stimulation (tDCS) of the primary motor cortex combined with somatosensory training against usual care including medication and physical therapy. The goal is to see if this strategy can significantly reduce PLP in a real-world setting compared to usual care alone.

How Is the Trial Designed?

Group I: Usual Care Experimental Treatment 1 Intervention

Usual care includes pharmacological treatments, physical therapy, occupational therapy and/or behavioral therapy that the subject is receiving.

Group II: M1 anodal home-based tDCS and somatosensory training Experimental Treatment 2 Interventions

Investigators will use the Soterix Medical 1X1 tDCS mini-CT stimulator device (© Soterix Medical Inc.) an home-based tDCS device used in several clinical trials with no adverse events. It sends a low-level current from the positive electrode, anode, to the negative electrode, cathode. During tDCS, low amplitude direct currents are applied via scalp electrodes and penetrate the skull to enter the brain. HB-TDCS will be combined with somatosensory training that will be performed during the self-administration of tDCS, including 20 sessions over 4 weeks.

M1 anodal home-based tDCS is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Direct Current Stimulation for:

• Phantom Limb Pain

Approved in European Union as Transcranial Direct Current Stimulation for:

• Phantom Limb Pain
• Neuropathic Pain

Who Is Running the Clinical Trial?

Spaulding Rehabilitation Hospital

Lead Sponsor

Trials

143

Recruited

11,200+

Published Research Related to This Trial

Anodal transcranial direct current stimulation (a-tDCS) applied to the primary motor cortex significantly increases sensory and pain thresholds in healthy individuals, with effect sizes of 22.19% and 19.28%, respectively.

In patients with chronic pain, a-tDCS applied to the primary motor cortex and dorsolateral prefrontal cortex resulted in a significant reduction in pain levels, with an average decrease in pain scores of 14.9% and 19.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does anodal transcranial direct current stimulation modulate sensory perception and pain? A meta-analysis study. Vaseghi, B., Zoghi, M., Jaberzadeh, S.[2022]

Transcranial direct current stimulation (tDCS) applied to the motor cortex significantly reduces phantom limb pain (PLP) in amputees, with effects lasting from hours to months depending on treatment frequency.

The review included six studies, indicating that while tDCS effectively alleviates PLP intensity, it does not appear to impact phantom limb sensations or psychiatric symptoms, suggesting a need for different treatment approaches for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in the management of phantom limb pain: a systematic review of randomized controlled trials. Navarro-López, V., Del-Valle-Gratacós, M., Fernández-Vázquez, D., et al.[2023]

Transcranial direct current stimulation (tDCS) can effectively reduce phantom limb pain (PLP) in amputees, with anodal stimulation of the primary motor cortex leading to a short-lasting decrease in pain sensations.

The study also found that nonpainful phantom sensations can be reduced by cathodal tDCS of the posterior parietal cortex, indicating that painful and nonpainful phantom sensations are distinct and can be targeted differently with tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor and parietal cortex stimulation for phantom limb pain and sensations. Bolognini, N., Olgiati, E., Maravita, A., et al.[2022]

This pilot study will evaluate the feasibility and preliminary efficacy of a home-based treatment combining anodal tDCS and motor imagery for managing phantom limb pain in 10 participants over 20 sessions.

The study aims to identify predictors of treatment response, which could help tailor future therapies for phantom limb pain and improve access to effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home-based transcranial direct current stimulation (tDCS) and motor imagery for phantom limb pain using statistical learning to predict treatment response: an open-label study protocol. Pacheco-Barrios, K., Cardenas-Rojas, A., de Melo, PS., et al.[2022]

Cerebellar transcranial direct current stimulation (ctDCS) effectively reduced paroxysmal pain and non-painful phantom limb sensations in 14 upper limb amputees, indicating its potential as a treatment for phantom limb pain.

The study showed that anodal ctDCS significantly dampened the amplitudes of laser-evoked potentials, suggesting it modulates nociceptive processing in the brain, although it did not affect phantom limb or stump pain compared to sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebellar Transcranial Direct Current Stimulation (ctDCS) Ameliorates Phantom Limb Pain and Non-painful Phantom Limb Sensations. Bocci, T., De Carolis, G., Ferrucci, R., et al.[2020]

In a study involving 112 amputees, transcranial direct current stimulation (tDCS) significantly reduced phantom limb pain compared to sham treatment, indicating its potential as an effective therapy.

Mirror therapy did not show any additional benefits or changes in motor cortex plasticity, suggesting that tDCS alone may be a more promising treatment for managing phantom limb pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Combined and Alone Transcranial Motor Cortex Stimulation and Mirror Therapy in Phantom Limb Pain: A Randomized Factorial Trial. Gunduz, ME., Pacheco-Barrios, K., Bonin Pinto, C., et al.[2023]

A 5-day treatment with active transcranial direct current stimulation (tDCS) over the motor cortex significantly reduced phantom limb pain (PLP) in 8 amputees, providing sustained relief for up to a week after treatment.

Patients experienced immediate pain relief and improved movement ability of their phantom limb during active tDCS sessions, while sham tDCS showed inconsistent effects, highlighting the potential of tDCS as a promising non-pharmacological treatment for chronic neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate and Sustained Effects of 5-Day Transcranial Direct Current Stimulation of the Motor Cortex in Phantom Limb Pain. Bolognini, N., Spandri, V., Ferraro, F., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35434309/

Home-based transcranial direct current stimulation (tDCS) and ... This study will evaluate the feasibility of a remotely home-based M1 anodal tDCS combined with motor imagery in phantom limb patients.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9009528/

Home-based transcranial direct current stimulation (tDCS) and ... This study will evaluate the feasibility of a remotely home-based M1 anodal tDCS combined with motor imagery in phantom limb patients.

3. journal.ppcr.org journal.ppcr.org/index.php/ppcrjournal/article/view/176

Home-based transcranial direct current stimulation (tDCS) and ... This study will evaluate the feasibility of a remotely home-based M1 anodal tDCS combined with motor imagery in phantom limb patients.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1526590015006069

Immediate and Sustained Effects of 5-Day Transcranial ... These results show that a 5-day treatment of motor cortex stimulation with tDCS can induce stable relief from PLP in amputees.

5. journal.ppcr.org journal.ppcr.org/index.php/ppcrjournal/article/view/176/135

View of Home-based transcranial direct current stimulation ... All participants will receive active anodal M1 tDCS combined with phantom limb motor imagery training. Our primary outcome will be the ...

6. epain.org epain.org/journal/view.html?uid=1917&vmd=Full

Effects of Transcranial Direct Current Stimulation on pain ... Conclusions: Our findings suggest that tDCS might be effective for fibromyalgia, migraine, and neuropathic pain associated with spinal cord ...