Effects of Transcutaneous Electrical Nerve Stimulation on Chemotherapy-Induced Peripheral Neuropathy

PRIMARY OBJECTIVE:

I. Obtain efficacy estimates of daily TENS on CIPN (European Organization for Research and Treatment of Cancer-CIPN20 [EORTC-CIPN20]) to inform the design of a phase III confirmatory trial.

SECONDARY OBJECTIVES:

I. Obtain efficacy estimates of TENS on individual CIPN symptoms (i.e., hot/burning pain, sharp/shooting pain, tingling, numbness, cramping (measured daily via 0 - 10 numeric rating scale [NRS]).

II. Evaluate the feasibility of conducting, within the University of Rochester Cancer Center (URCC) National Cancer Institute Community Oncology Research Program (NCORP) network, a multisite, modified double-blind randomized control trial (RCT) of TENS for CIPN with physiologic assessments of descending inhibition (i.e., conditioned pain modulation [CPM] test) by assessing the proportions of (a) screened patients who enroll, (b) randomized participants who adhere to the treatment and complete the primary assessment, and (c) randomized participants who complete the CPM test.

EXPLORATORY OBJECTIVES:

I. Investigate the potential effects of TENS on balance, physical function, descending inhibition, lower limb sensation, and anxiety and depression.

II. Establish data to support the construct validity of the Treatment-Induced Neuropathy Assessment Scale (TNAS) and CIPN symptom inventory daily diary by comparison to the EORTC-CIPN20, which is the most commonly used measure of CIPN.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients wear an active wireless TENS device 5 hours daily for up to 6 weeks in the absence of unacceptable toxicity.

GROUP II: Patients wear a placebo wireless TENS device 5 hours daily for up to 6 weeks in the absence of unacceptable toxicity.

Inclusion criteria

• Have completed treatment with a platinum agent, taxane, vinca alkaloid, or bortezomib at least 3 months prior to registration
• Have a clinical diagnosis of CIPN from their physician or physician designee based on the following criteria: bilateral (i.e., present on both sides of the body), abnormal sensory symptoms in their feet or legs (e.g., hot/burning pain, sharp/shooting pain, numbness, tingling, cramping)
• Report at least 1 non-painful symptom associated with CIPN in their lower limbs (e.g., tingling, burning that isn't reported as painful, numbness)
• Report at least 2 of the following symptoms in their lower limbs (at their worst) as at least 4 out of 10 on a 0 - 10 NRS: hot/burning pain, sharp/shooting pain, numbness, tingling, cramping at visit 1 (i.e., week -1). Use the CIPN Symptom Inventory - week recall form (questions 1-5 ONLY) to assess these symptoms at screening
• Be willing and able not to start any new analgesic medications or change the dosages of any current analgesic medications (except acetaminophen [Tylenol] or non-steroidal anti-inflammatory drugs [NSAIDs] [i.e., ibuprofen (Advil, Motrin), naproxen (Aleve)]) for the duration of the study
• Be able to read English (i.e., is not illiterate, can speak English, and is not blind)
• Have access to a smart phone or device with an Apple or Android operating system that can be used to access the TENS device's application (App) and ability to connect to the internet on a daily basis during the trial

Exclusion criteria

• Have pre-existing neuropathy of any cause documented in their medical record prior to the start of chemotherapy or respond "yes" to the question "Did you have frequent numbness, tingling, sharp/shooting pain, hot/burning pain, or cramping in your feet before you started your chemotherapy?"
• Have unilateral CIPN symptoms (i.e., symptoms occur on predominantly only one side of the body)
• Be currently using a TENS device for any other reason
• Be currently taking, or have taken in the past 3 months, medications known to cause neuropathy in a significant portion of patients
• Have an acute and symptomatic lower extremity deep vein thrombosis (DVT) (treated DVT with resolution of symptoms is acceptable for enrollment)
• Lower extremity edema that is 2+ or greater (i.e., slight indentation that takes less than 15 seconds to rebound)
• Have started a new prescription pain medication or altered dosages of a prescription pain medication within the last 2 weeks
• Have lower extremity wounds or ulcers
• Have a cardiac pace maker or defibrillator
• Have epilepsy
• Have a leg that is too small or too large for the TENS device to fit securely
• Have missing lower limbs or amputations
• Have impaired decision making capacity (i.e., requires a legally authorized representative or health care proxy)
• Be pregnant or planning to get pregnant before expected completion of the study