Scrambler Therapy for Peripheral Neuropathy

Overseen By Leslie Fortin, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must be taking: Duloxetine

Must not be taking: MAOIs, Gabapentin

Disqualifiers: Children, Pregnant, Severe depression, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Scrambler therapy, a non-invasive pain treatment, combined with duloxetine can relieve nerve pain from chemotherapy more effectively than duloxetine alone. The aim is to reduce pain and improve daily functioning for individuals with chemotherapy-induced peripheral neuropathy (CIPN), which causes tingling and numbness. The study will compare two groups: one receiving only duloxetine and the other receiving both Scrambler therapy and duloxetine. Suitable participants have cancer-related nerve pain scoring at least 4 out of 10, have recently completed chemotherapy, and are already taking duloxetine. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you be on duloxetine for at least 4 weeks before starting. If you are taking gabapentin, you must be able to stop it, as the trial requires tapering off gabapentin. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What prior data suggests that Scrambler Therapy is safe for peripheral neuropathy?

Research has shown that Scrambler therapy is generally safe for treating chemotherapy-induced peripheral neuropathy (CIPN), a type of nerve damage from chemotherapy. This treatment uses electrical signals to change pain messages and is well-tolerated by most patients. Side effects are rare and usually mild, such as minor skin irritation.

Duloxetine, a medication often used for nerve pain, is also part of this study. The FDA has already approved it for similar conditions, indicating its safety for humans. Side effects from duloxetine, such as nausea or tiredness, are usually manageable.

Since this trial is in an early phase, the researchers are still collecting safety data. However, previous research suggests that the combination of Scrambler therapy and duloxetine is well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Scrambler Therapy for peripheral neuropathy because it offers a non-invasive approach that aims to retrain the brain's perception of pain, which is different from conventional medications like Duloxetine that primarily work by altering neurotransmitter levels. Scrambler Therapy uses electrical signals to replace pain signals with non-pain information, potentially providing relief without the side effects associated with pharmacological treatments. This novel mechanism could offer faster and more effective pain relief, making it a promising option for patients suffering from neuropathy.

What evidence suggests that Scrambler therapy might be an effective treatment for peripheral neuropathy?

Research has shown that Scrambler therapy may help treat nerve pain caused by chemotherapy, known as chemotherapy-induced peripheral neuropathy (CIPN). In one study, participants reported a 59% decrease in their pain levels, with scores dropping from 5.81 to 2.38 on a standard pain scale. Scrambler therapy sends electrical signals to the nerves, which can block pain messages. It has also proven more effective than other methods like transcutaneous electrical nerve stimulation, another type of electrical therapy. In this trial, some participants will receive Scrambler therapy combined with Duloxetine, while others will receive Duloxetine alone. These findings suggest that Scrambler therapy could be a strong option for reducing pain related to CIPN. ^{2 3 5 6 7}

Who Is on the Research Team?

Marcin Chwistek, MD

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals experiencing pain due to chemotherapy-induced peripheral neuropathy (CIPN). Participants should be currently receiving or have completed chemotherapy. They must not have other medical conditions that could interfere with the study or be using certain medications that affect CIPN assessment.

Inclusion Criteria

At least CTCAE version 5.0 grade 2 neuropathies

I can perform all my daily activities without help.

Score of at least 4 on the Douleur-Neuropathique-en-4 Questions (DN4) questionnaire

Exclusion Criteria

Patients with severe depression, suicidal ideation, bipolar disease, alcohol abuse, a major eating disorder

I have epilepsy that is not well-controlled.

Pregnant or nursing patients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Scrambler therapy with duloxetine or duloxetine-based usual care

8 weeks

Weekly visits for therapy sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Scrambler Therapy

Trial Overview The study tests if Scrambler therapy combined with duloxetine results in better pain relief for CIPN than just duloxetine-based usual care. Pain reduction is measured by questionnaires and physical exams, focusing on whether patients achieve at least a 50% drop in pain scores after treatment.

How Is the Trial Designed?

Group I: Duloxetine Group Experimental Treatment 1 Intervention

Patients will be treated with Duloxetine as per Specialized Outpatient Palliative Care SOPC standard neuropathy treatment protocol

Group II: Scrambler + Duloxetine Active Control 2 Interventions

Patients' pharmacological treatment of their CIPN (including the management of duloxetine and other co-analgesics) will follow SOPC standard neuropathy treatment protocol

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Published Research Related to This Trial

Diabetic neuropathy significantly impacts patients' quality of life and is linked to serious complications like foot ulcers and increased mortality, highlighting the need for effective drug treatments.

Randomized clinical trials (RCTs) evaluating treatments for diabetic neuropathy have historically been of poor quality, emphasizing the importance of well-designed studies that consider factors like neuropathy stage, outcome measures, and long-term effects to ensure meaningful results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials for drugs against diabetic neuropathy: can we combine scientific needs with clinical practicalities? Ziegler, D., Luft, D.[2019]

Scrambler therapy (ST) significantly reduced pain levels in adolescents with chemotherapy-induced peripheral neuropathy (CIPN), with pain scores dropping from an average of 9.22 to 0.11 after treatment, indicating strong efficacy.

The therapy also improved quality of life across multiple areas, including general activity, mood, walking ability, sleep, and social relationships, with no reported side effects, suggesting it is a safe and effective option for managing CIPN in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy-induced peripheral neuropathy in adolescents: A preliminary study. Tomasello, C., Pinto, RM., Mennini, C., et al.[2019]

Scrambler therapy (ST) is a promising noninvasive treatment for chronic neuropathic and cancer pain, utilizing artificial neurons to transmit 'non-pain' signals through C fiber receptors.

In three case studies of patients suffering from chemotherapy-induced peripheral neuropathy, scrambler therapy demonstrated successful pain relief, highlighting its potential as an alternative when traditional pain management methods are ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scrambler therapy: A ray of hope for refractory chemotherapy-induced peripheral neuropathy. Ahuja, D., Bharati, SJ., Gupta, N., et al.[2020]

Citations

1. ons.org ons.org/sites/default/files/2025-05/pn-evaluation-table_scrambler-therapy-2025.pdf

Peripheral Neuropathy Evaluation Table 2025: Scrambler ... All of the included studies provided data on at least one feasibility outcome. Seven studies provided information on the acceptability of the interventions.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4383262/

Pilot evaluation of Scrambler therapy for the treatment ... The first published trial of Scrambler therapy specifically for the treatment of CIPN reported a reduction in pain score of 59 % (5.81±1.11 to 2.38±1.82) by the ...

3. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2025.1607102/full

The treatment of chemotherapy-induced peripheral ... Scrambler therapy (ST) is a peripheral, non-invasive neuromodulation technique, which uses transcutaneous electrical stimulation to modulate pain signals.

4. jpsmjournal.com jpsmjournal.com/article/S0885-3924(20)30895-2/fulltext

Randomized Trial of Scrambler Therapy for Chemotherapy ... Scrambler therapy appears to outperform transcutaneous electrical nerve stimulation for treating chemotherapy-induced peripheral neuropathy.

5. asco.org asco.org/abstracts-presentations/ABSTRACT217405

Scrambler therapy for established chemotherapy-induced ... Scrambler therapy for established chemotherapy-induced neuropathy: A randomized phase II trial. ; ≥50% reduction in tingling scores, 14 days, 48%, 24%, 0.08.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29630779/

Scrambler therapy efficacy and safety for neuropathic pain ... Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy-induced peripheral neuropathy in adolescents: A preliminary study.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05357469

Study Details | NCT05357469 | Innovative Treatment of ... To evaluate the efficacy and safety of Scrambler therapy (ST) for chemotherapy-induced painful peripheral neuropathy (CIPN), and the impact of ST on ...