A phase III confirmatory clinical trial of daily, wireless, home-based TENS for painful peripheral neuropathy

About This Grant

PROJECT SUMMARY Neurotoxic chemotherapy agents are used to treat common cancers including breast, gastrointestinal, lung, ovarian, and myeloma, which together made up ~40% of new U.S. cancer cases in 2023. Approximately 60% of patients who receive neurotoxic chemotherapy develop chemotherapy induced peripheral neuropathy (CIPN). CIPN causes burning/shooting pain, cramping, tingling, and numbness in the limbs. It is associated with impaired balance, walking, and sleep. Few, only minimally effective treatments are available for painful CIPN; these pharmacologic treatments are rarely evidenced-based and potentially addictive. Because research suggests that CIPN is caused, at least in part, by abnormal neuronal processing in the central and peripheral nervous systems, including increased neuronal excitability, we evaluated the effects of transcutaneous electrical nerve stimulation (TENS) on CIPN sensory symptoms in a recent phase II trial. The results of that trial suggest that TENS relieves pain associated with CIPN and that conducting a large placebo-controlled, randomized clinical trial (RCT) of TENS for painful CIPN in the NCI Community Oncology Research Program (NCORP) network is feasible. It also demonstrates that over half of CIPN patients interested in joining a symptom trial have moderate to severe pain. A rigorous, confirmatory, phase III, multi-site, blinded RCT of TENS for painful CIPN that leverages the NCORP Network is proposed. The TENS device is a home-delivered, App- controlled, wireless unit that can be worn throughout the day and during physical activity. It is ideal for maximizing adherence in clinical trials and for optimizing dissemination in clinical practice. The primary aim of the study is to confirm efficacy of TENS on painful CIPN using a personalized outcome defined for each participant as the mean severity of the neuropathic pain qualities that they rate as ≥ 4 out of 10 at baseline. Secondary aims include (1) evaluating the efficacy of TENS on functional impairments often associated with painful CIPN (i.e., walking ability, balance, and sleep disturbance), (2) evaluating long-term (6-month) usage rates of TENS, and (3) exploring predictors of 6-week treatment response, including initial response (i.e., at 1-2 weeks), demographic and clinical variables, pain catastrophizing, expectations for response, and neuronal excitability (as measured via quantitative sensory testing). Establishing effective, non-pharmacologic treatments for painful CIPN will help to mitigate suffering in cancer survivors while avoiding potentially harmful side effects caused by many currently available analgesics or invasive procedures associated with more expensive modes of stimulation. This trial is necessary to support inclusion of TENS, a safe, non-pharmacologic, non-invasive, and inexpensive therapy in CIPN treatment guidelines and promote dissemination of this potentially important therapy to patients and the clinicians who treat them.