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Comparison of High Tone Therapy and TENS Therapy (HIT-CIPN)

P

Paracelsus Medical University (PMU)

Status

Completed

Conditions

Peripheral Nervous System Problem

Treatments

Device: transcutaneous electrical nerve stimulation (TENS) therapy
Device: high tone external muscle stimulation

Study type

Interventional

Funder types

Other

Identifiers

NCT03978585
415-E/2376/7-2018

Details and patient eligibility

About

This study evaluates the efficacy of home-based high tone external muscle stimulation (HTEMS) compared to transcutaneous electrical nerve stimulation (TENS) in chemotherapy-induced peripheral neuropathy (CIPN). One half of the participants will receive TENS therapy, the other half will receive High tone external muscle Stimulation. It is expected that HTEMS improves symptoms of CIPN.

Full description

One of the most common adverse side effects of chemotherapeutic agents especially in taxanes, platins or vinca alkaloids is chemotherapy-induced peripheral neuropathy (CIPN). Prevalence of CIPN was reported in 30% to 40% of patients treated with neurotoxic chemotherapy and may be transient or permanent. It appears predominantly as sensory neuropathy and affects the peripheral parts of the extremities in a "stocking and glove"-distribution. CIPN often presents with symptoms like paresthesia, pain, numbness or tingling, but motor symptoms can occur as well. Symptoms of CIPN may lead to dose reduction or even early cessation of chemotherapy and therefore may affect overall survival in cancer patients. Currently, no evidence-based treatment (drug or non-drug therapy) is available for CIPN. Several approaches to manage peripheral neuropathy have been proposed, but evidence showing a benefit of these procedures regarding clinically relevant endpoints is scarce. One promising approach to ease CIPN symptoms is the application of electrotherapy. Different types of electrical sensory interventions have been explored in the literature e.g. transcutaneous electrical nerve stimulation (TENS) and high-tone external muscle stimulation (HTEMS).TENS is used in medical settings and in self-administration of patients at home. In TENS only the frequency is modulated. The device sends electrical impulses through conductive rubber electrodes to the skin of the impaired region. The applied frequencies range from 2 to 120 Hertz. The pain region must be in the middle of the two electrodes, which have a maximum distance of 20cm. In contrast to the TENS therapy, the HTEMS operates in-depth directly on the muscle and produces pleasant, but intense and thus effective contractions. Additionally in HTEMS, the amplitude and the frequency are modulated simultaneously. The applied frequencies range continuously from 4096 to 32768 Hertz. Different frequencies activate structures of different size. For this reason, it is important to offer a broad spectrum of frequencies. The electrical stimulation is applied by using conductive rubber electrodes. On the upper limbs as well as on the lower limbs the electrodes are positioned as far as possible proximal and distal. During the treatment the muscle is stimulated to contraction through intervals. One interval consists of three seconds ramp-up time (intensity rises), three seconds holding time (intensity maintains on maximum) and three seconds pause (no stimulation).

The application of HTEMS has been shown to be more effective than TENS in the therapy of diabetic peripheral neuropathy. Furthermore, HTEMS demonstrated improvement in pain, discomfort, sleep disturbance and quality of life in patients with end-stage renal disease due to uremic peripheral neuropathy. So far, little research on HTEMS or TENS in CIPN has been carried out, even if this approach is used in clinical practice. The aim of this study is to evaluate the effect and feasibility of home-based HTEMS in patients with chemotherapy-induced peripheral neuropathy.

This pilot study will be based on a single blinded randomised controlled trial study design with an observation time of eight weeks. Patients with cancer receiving a taxan-or platin-based chemotherapy and symptoms of CIPN will be included. Subjects will be stratified by treatment delivery, taxan and platin. The therapy will start after completed adjuvant chemotherapy after a time period of 4 weeks minimum to exclude patients with spontaneous remission of CIPN and in order to reduce the effect of any known or unknown biases related to the treatment regime. Potential study participants will receive information about the study as soon as symptoms occurred to plan inclusion, randomisation and allocation of appointments. Patients will receive a TENS or HTEMS device after randomisation. Participants who are allocated to the control intervention group will receive TENS therapy. The participant is educated for home-based therapy and the treatment should be used daily for 30 minutes for 8 weeks. Additionally, participants' compliance will be checked by reading out the tool box. Participants are asked to fill out the EORTC CIPN 20 (chemotherapy-induced) and EORTC QLQ-C30 (quality of life) questionnaire at baseline and after 8 weeks. Clinical examination encompassing vibration sensibility, tendon reflexes, temperature sensibility perception of touch and muscel strength will be conducted at the same time points.

The investigators would prefer not to constrain patients to specific daily time points and disturb their individual rhythm. Therefore, the investigators recommend performing the intervention at a regular daily time point adapted to the individual daily routine. The primary endpoint is a change in the EORTC-QLQ-CIPN20 score during the eight weeks of intervention. For our primary endpoint the investigators will use an intention-to-treat analysis according to the CONSORT statement. Furthermore, the investigators will analyse the intensity of intervention (compliance) and the effect on the primary endpoint (for example comparison of infrequently and frequently use of device). A minimum use on 5 of 7days per week is required.

Enrollment

51 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

  • Inclusion criteria:

    • Age 18 years or older
    • Histologically proven cancer
    • ECOG performance score 0-1(Eastern Cooperative Oncology Group)
    • Completed neoadjuvant or adjuvant chemotherapy with taxane or platin
    • Minimum time distance to neurotoxic agent 4 weeks, maximum 24 weeks
    • Clinical diagnosis of CIPN ≥Grade 1 according to CTCAE during or after completion of chemotherapy
    • Ability to complete questionnaires by themselves or with assistance
    • Ability to understand the study regimen, its requirements, risks, and discomforts, and ability and willingness to sign an informed consent form

Exclusion Criteria:

  • Ongoing treatment with antitumor treatments with potential neurotoxic side effects (e.g. platins, taxanes, vinca alkaloids, bortezomib or thalidomide)
  • Completed chemotherapy with neurotoxic side effects other than taxane or platin
  • Pre-existing clinically manifest peripheral neuropathy prior to start of chemotherapy (e.g. caused by radiation or malignant plexopathy, lumbar or cervical radiculopathy, carpal tunnel syndrome, B12 deficiency, AIDS, monoclonal gammopathy, diabetes, heavy metal poisoning amyloidosis, syphilis, hyperthyroidism or hypothyroidism, inherited neuropathy, etc.)
  • Peripheral arterial occlusive disease > Grade 1
  • Skin conditions such as open sores preventing proper application of the electrodes
  • Patients with implantable medical electronic devices (e.g. pace maker, Implantable Cardioverter Defibrillator - ICD, catheter, etc.)
  • Patients with myocard damages or cardiac arrhythmia
  • Patients with epilepsy
  • Patients with febrile illnesses or acute infectious diseases
  • Pregnancy

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

51 participants in 2 patient groups

HTEMS Arm
Experimental group
Description:
High tone therapy (home based) daily for 30 minutes on at least 5 of 7 days per week
Treatment:
Device: high tone external muscle stimulation
Device: transcutaneous electrical nerve stimulation (TENS) therapy
TENS Arm
Active Comparator group
Description:
TENS therapy (home based) daily for 30 minutes on at least 5 of 7 days per week
Treatment:
Device: high tone external muscle stimulation
Device: transcutaneous electrical nerve stimulation (TENS) therapy

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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