Randomized Trial of Scrambler Therapy for Chemotherapy-Induced Peripheral Neuropathy: Crossover Analysis

J Pain Symptom Manage. 2021 Jun;61(6):1247-1253. doi: 10.1016/j.jpainsymman.2020.11.025. Epub 2020 Nov 27.


Context: Preliminary trials report that Scrambler Therapy, a form of electroanalgesia, may improve discomfort from chemotherapy-induced peripheral neuropathy (CIPN).

Objective: The objective of this phase II, randomized controlled trial was to evaluate the efficacy of Scrambler therapy vs. transcutaneous electrical nerve stimulation (TENS) in treating CIPN.

Methods: Fifty patients were accrued for the first half of this two-part, crossover trial consisting of a 2-week treatment period with either Scrambler or TENS, followed by an 8-week observation period, and then crossover treatment. Twenty-two patients proceeded to the crossover phase. The primary means of assessment was patient-reported outcomes, including symptom severity scales and Global Impression of Change questionnaires. Symptoms were assessed daily during the treatment period and weekly during an 8-week observation period.

Results: A 50% or greater reduction in primary symptom (pain or tingling) score on the last day of treatment was achieved by 6 of 10 Scrambler-treated patients (60%) and 3 of 12 TENS-treated patients (25%) after crossover (P = 0.11). By day 4 of treatment, the two arms diverged with respect to mean change in primary symptom score; this effect was largely carried through to the end of the two-week treatment period. Similarly, Scrambler therapy appeared better than TENS when assessed by Global Impression of Change for neuropathy, pain, and overall quality of life.

Conclusions: Similar findings from the initial randomization and crossover phases of this study support further evaluation of the efficacy of Scrambler therapy in alleviating CIPN symptoms. Evaluation in a larger, randomized controlled trial with standardized treatment is warranted.

Trial registration: ClinicalTrials.gov NCT02722434.

Keywords: Scrambler therapy; antineoplastic agents; chemotherapy-induced peripheral neuropathy; transcutaneous electric nerve stimulation.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Cross-Over Studies
  • Humans
  • Pain Management
  • Peripheral Nervous System Diseases* / chemically induced
  • Peripheral Nervous System Diseases* / therapy
  • Quality of Life


  • Antineoplastic Agents

Associated data

  • ClinicalTrials.gov/NCT02722434