Scrambler Therapy With Duloxetine-based Usual Care vs Duloxetine-based Usual Care for Chemotherapy-induced Peripheral Neuropathy: A Randomized Phase II Pilot Trial.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequently experienced and often persistent side effect of many commonly utilized chemotherapy regimens. This list of agents includes platinum agents, taxanes, vinca alkaloids, and bortezomib. The estimated incidence of this toxicity, according to some sources, can be as high as 68.1% (95% CI: 57.7-78.4%) among patients with exposure to antineoplastic agents commonly known to cause neuropathy. Chemotherapy-induced peripheral neuropathy can be significant for many patients and can limit their ability to perform activities of daily living (ADLs). It is a frequent dose-limiting complication around which many oncologists must navigate.

While many agents have been studied to mitigate this complication, few have been shown to be effective or clinically significant. Duloxetine, perhaps the agent with the most evidence for use, showed a mean decrease in a patient's average pain score on the Brief Pain Inventory-Short Form (BPI-SF) of 1.06 versus 0.34 in the control arm (on an 11-point scale) (p = 0.003). Many other therapies have been proposed, such as gabapentin, tricyclic antidepressants (TCAs), cannabinoids, lidocaine, oral glutamine, cryotherapy, acupuncture, massage, and exercise-each with varying degrees of effectiveness. Despite these numerous therapies, duloxetine is the current standard of care for treating neuropathic pain, as evidenced by its inclusion in the National Comprehensive Cancer Network guidelines for the management of adult cancer pain.

Scrambler therapy is a novel treatment modality that has a growing body of evidence for neuropathic pain. It was originally developed by investigators at the University of Rome Tor Vergata following a series of preliminary clinical trials conducted from 1999 to 2006, involving 2,297 cases of various types of medication-resistant neuropathic pain. The machine uses five artificial neurons to transmit strings of "non-pain" signals based on a proprietary algorithm.

The investigators hypothesize that Scrambler therapy with duloxetine, compared to duloxetine-based usual care, will result in greater improvement in CIPN as measured by the BPI-Short Form. In addition, the investigators will further assess pain using the EORTC CIPN-20 and determine whether Scrambler therapy will result in improved levels of function as measured with the PDQ, and decreased need for opioid medications.

Our primary objective is to investigate whether Scrambler therapy with duloxetine is superior to duloxetine-based usual care in helping patients achieve at least a 50% reduction in pain scores when comparing the cross-sectionally measured "average" pain score (question 5 on the BPI) at day 35 to the score at baseline (day 1). The post-crossover outcomes will be included in the primary analysis. The first measurement on day 1 and the last measurement on day 35 will be used.