Testing the Effects of Transcutaneous Electrical Nerve Stimulation (TENS) on Chemotherapy-Induced Peripheral Neuropathy (CIPN)

• ClinicalTrials.gov Identifier: NCT04367480
• Recruitment Status: Completed
• First Posted: April 29, 2020
• Last Update Posted: December 12, 2022
• Sponsor: University of Rochester NCORP Research Base
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Jennifer Gewandter, University of Rochester

Tracking Information

• First Submitted Date: April 21, 2020
• First Posted Date: April 29, 2020
• Last Update Posted Date: December 12, 2022
• Actual Study Start Date: September 10, 2020
• Actual Primary Completion Date: October 3, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2020)

Chemotherapy-induced peripheral neuropathy (CIPN) symptoms [ Time Frame: After 6 weeks of device use ]

Measured by the mean European Organization for Research and Treatment of Cancer-CIPN20 (EORTC-CIPN20). The effects of transcutaneous electrical nerve stimulation (TENS) on CIPN will be estimated using analysis of covariance (ANCOVA).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 24, 2020)

• Effect of TENS on hot/burning and sharp/shooting pain [ Time Frame: At baseline and at week 6 ]
  Measured by the CIPN Symptom Inventory; numeric rating scale of 0-10. The effects of transcutaneous electrical nerve stimulation (TENS) on hot/burning and sharp/shooting pain will be estimated using analysis of covariance (ANCOVA).
• Effect of TENS on numbness [ Time Frame: At baseline and at week 6 ]
  Measured by the CIPN Symptom Inventory; numeric rating scale of 0-10. he effects of transcutaneous electrical nerve stimulation (TENS) on numbness will be estimated using analysis of covariance (ANCOVA).
• Effect of TENS on tingling [ Time Frame: At baseline and at 6 weeks ]
  Measured by the CIPN Symptom Inventory; numeric rating scale of 0-10. he effects of transcutaneous electrical nerve stimulation (TENS) on tingling will be estimated using analysis of covariance (ANCOVA).
• Effect of TENS on cramping [ Time Frame: At baseline and 6 weeks ]
  Measured by the CIPN Symptom Inventory; numeric rating scale of 0-10. he effects of transcutaneous electrical nerve stimulation (TENS) on cramping will be estimated using analysis of covariance (ANCOVA).

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 24, 2020)

• Effect of TENS on balance (on Short Physical Performance Battery [SPPB]) [ Time Frame: At baseline and 6 weeks ]
  Estimated using ANCOVA.
• Descending inhibition (on Conditioned Pain Modulation [CPM] test) [ Time Frame: At baseline and 6 weeks ]
  Estimated using ANCOVA. Descriptive statistics will be used to characterize the distribution of descending inhibition as measured by CPM at baseline. ANCOVA analysis will be used to investigate whether baseline descending inhibition predicts the effect of TENS on CIPN.
• Effect of TENS on physical function [ Time Frame: At baseline and 6 weeks ]
  Measured by Patient Reported Outcomes Measurement Information System (PROMIS) short form. 4 physical activity items are rated from 1-5 corresponding to "Cannot Do" to "Without any difficulty" and 4 items regarding how health limits activity are rated from 1-5 "Cannot Do" to "Not at all". Estimated using ANCOVA.
• CIPN-interference in daily life [ Time Frame: At baseline and 6 weeks ]
  Measured by the CIPN-interference in daily life questionnaire which uses 0-10 numeric rating scale [0 = does not interfere, 10 = completely interferes]. Estimated using ANCOVA.
• CIPN [ Time Frame: At baseline and 6 weeks ]
  Will be measured by Treatment-Induced Neuropathy Assessment Scale (TNAS) and CIPN symptom inventory composite measure. The correlation of descending inhibition with CIPN severity (via CIPN20, TNAS, and symptom numeric rating scale [NRS] scores) will be evaluated using a Spearman's correlations. Estimated using ANCOVA.
• Depression and anxiety [ Time Frame: At baseline and 6 weeks ]
  Estimated using ANCOVA.
• Analgesic use [ Time Frame: At baseline and 6 weeks ]
  The proportion of participants who decreased "as-needed" usage of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) (defined as taking acetaminophen or NSAIDs, on average, at least 30% fewer days per week in the last week of the trial compared to the baseline week) will be compared by groups using a chi-square test.
• Patient reported change in CIPN symptoms [ Time Frame: At baseline and 6 weeks ]
  The proportion of participants who report, for the impression of change in CIPN symptoms question "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", and "very much worse") will be compared between treatment groups using a Cochran Armitage Trend Test.
• Patient sensation threshold from monofilament test [ Time Frame: At baseline and 6 weeks ]
  The proportion of participants whose sensation threshold from the monofilament test improved will be reported together with the 95% confidence interval (CI) and tested against the null hypothesis of no improvement.
• Percentage of participants and outcome assessors that correctly identify the group to which the participant was assigned [ Time Frame: After 6 weeks of device use ]
  Descriptive statistics and 95% CIs will be used to assess the percentage of participants and outcome assessors that correctly identify the group to which the participant was assigned as well as the basis for the guesses.
• Test, re-test reliability for CPM test [ Time Frame: After 6 weeks of device use ]
  Will be evaluated using intraclass correlation coefficients (ICCs). Test, re-test reliability for the lower limb sensation threshold test will be measured using Kappa statistics.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Testing the Effects of Transcutaneous Electrical Nerve Stimulation (TENS) on Chemotherapy-Induced Peripheral Neuropathy (CIPN)
• Official Title: Wireless Transcutaneous Electrical Nerve Stimulation (TENS) for Chemotherapy-Induced Peripheral Neuropathy: A Phase II Clinical Trial
• Brief Summary: This phase II trial studies the effects of transcutaneous electrical nerve stimulation (TENS) for the treatment of peripheral neuropathy caused by chemotherapy, often called chemotherapy-induced peripheral neuropathy (CIPN). Peripheral neuropathy refers to the conditions that result when nerves that carry messages to and from the brain and spinal cord from and to the rest of the body are damaged or diseased. The TENS device emits high frequency electrical stimulation through the skin and may provide relief from chronic pain.

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Supportive Care
• Condition: Chemotherapy-Induced Peripheral Neuropathy

Intervention

• Device: Placebo Administration
  Wear placebo TENS device
• Other: Questionnaire Administration
  Ancillary studies
• Device: Transcutaneous Electrical Nerve Stimulation
  Wear active TENS device
  Other Names:

  • TENS
  • transcutaneous electric nerve stimulation

Study Arms

• Experimental: Group I (TENS)
  Patients wear an active wireless TENS device 5 hours daily for up to 6 weeks in the absence of unacceptable toxicity.
  Interventions:

  • Other: Questionnaire Administration
  • Device: Transcutaneous Electrical Nerve Stimulation
• Placebo Comparator: Group II (placebo TENS)
  Patients wear a placebo wireless TENS device 5 hours daily for up to 6 weeks in the absence of unacceptable toxicity.
  Interventions:

  • Device: Placebo Administration
  • Other: Questionnaire Administration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 9, 2022): 151
• Original Estimated Enrollment (submitted: April 24, 2020): 126
• Actual Study Completion Date: October 3, 2022
• Actual Primary Completion Date: October 3, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04367480
• Other Study ID Numbers: URCC19085; NCI-2019-07566 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); URCC19085 ( Other Identifier: University of Rochester NCORP Research Base ); URCC-19085 ( Other Identifier: DCP ); URCC-19085 ( Other Identifier: CTEP ); R21CA235389 ( U.S. NIH Grant/Contract ); UG1CA189961 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jennifer Gewandter, University of Rochester
• Original Responsible Party: Gary Morrow, University of Rochester NCORP Research Base, Director, URCC NCORP Research Base
• Current Study Sponsor: University of Rochester NCORP Research Base
• Original Study Sponsor: Gary Morrow
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jennifer Gewandter; University of Rochester NCORP Research Base

• PRS Account: University of Rochester
• Verification Date: December 2022