Scrambler Therapy in the Treatment of Chronic Chemotherapy-Induced Peripheral Neuropathy

A Pilot Randomized Sham-Controlled Trial of MC5-A Calmare Therapy (Scrambler Therapy) in the Treatment of Chronic Chemotherapy-Induced Peripheral Neuropathy (CIPN)

The purpose of this study is to see if Scrambler Therapy with the Calmare MC5-A machine will relieve chemotherapy induced peripheral neuropathy (CIPN).

Scrambler Therapy is a method of pain relief given with common electrocardiography (ECG) skin electrodes. The electrodes are placed on the body in pairs, and the Scrambler Therapy machine directs electrical signals across the field to simulate non-pain information.

Based on other studies, we think that we relieve pain with the Scrambler therapy device, but it has not been tested in a setting such as this one. This means that some of the pain relief could be due to placebo effect, or the CIPN pain going away on its own. In this study we want to compare the Scrambler Therapy with the sham therapy (the therapy that does not use the electrical signals). We hope that this study will help us determine if the Scrambler device really helps patients with CIPN.

Cancer patients with chronic, chemotherapy-related pain of 4 or more (on a 0-10 scale) for at least 3 months may be eligible to join this study.

Study Overview

• Status: Completed
• Conditions: Neuropathy
• Intervention / Treatment: Device: Scrambler Therapy; Device: Sham Therapy

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287-0013
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women, 18 years of age or older with cancer
• English speakers
• Lower extremity CIPN neuropathy: Received neurotoxic chemotherapy (including taxanes-such as paclitaxel or docetaxel, or platinum-based compounds such as carboplatin or cis-platinum or oxaliplatin, or vinca alkaloids such as vincristine, vinblastine, or vinorelbine, or proteosome inhibitors such as bortezimib).
• Pain or symptoms of lower extremity peripheral neuropathy of >3 month's duration attributed to chemotherapy-induced peripheral neuropathy
• An average daily pain rating of > 4 out of 10
• Life expectancy >3 months
• ECOG Performance Status 0, 1, 2, or 3
• Patient understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form

Exclusion Criteria:

• Any of the following: pregnant women, nursing women, women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, abstinence, etc.).
• Use of an investigational agent for pain control concurrently or within the past 30 days
• History of an allergic reaction or previous intolerance to transcutaneous electronic nerve stimulation
• Patients with implantable drug delivery systems, e.g. Medtronic Synchromed
• Patients with heart stents or metal implants such as pacemakers, automatic defibrillators, cochlear implants, aneurysm clips, vena cava clips and skull plates. (Metal implants for orthopedic repair, e.g. pins, clips, plates, cages, joint replacements are allowed)
• Patients with a history of myocardial infarction or ischemic heart disease within the past six months
• Patients with history of epilepsy, brain damage, or symptomatic brain metastases
• Prior celiac plexus block, or other neurolytic pain control treatment
• Other identified causes of painful parasthesias existing prior to chemotherapy (e.g., radiation or malignant plexopathy, lumbar or cervical radiculopathy, pre-existing peripheral neuropathy of another etiology: e.g., carpal tunnel syndrome, B12 deficiency, AIDS, monoclonal gammopathy, diabetes, heavy metal poisoning amyloidosis, syphilis, hyperthyroidism or hypothyroidism, inherited neuropathy, etc.) that might be responsible for the patient's current neuropathic symptoms
• Skin conditions such as open sores that would prevent proper application of the electrodes
• Other medical or other condition(s) that in the opinion of the investigators might compromise the objectives of the study
• Currently receiving anti-convulsants (such as gabapentinoids, e.g. gabapentin (Neurontin) or pregabalin (Lyrica). Because of data that support that patients do not do as well when on gabapentin or pregabalin, all patients on these medications will be weaned off them prior to study initiation. The study team will provide instructions on how to do this

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Scrambler Therapy; The device is a cutaneous electrical stimulator that uses electrodes placed on the skin similar to an electrocardiogram (EKG) machine, feeling similar to a tingling or bee-sting like sensation during the therapy. The electrodes are placed in areas thought to help relieve pain associated with chemotherapy-induced peripheral neuropathy.	Device: Scrambler Therapy; Other Names: MC5-A Calmare Therapy; Scrambler ST 5 TENS Device
Sham Comparator: Sham Therapy; The device is a cutaneous electrical stimulator that uses electrodes placed on the skin similar to an electrocardiogram (EKG) machine, feeling similar to a tingling or bee-sting like sensation during the therapy. The electrodes are placed in areas not thought to help relieve pain associated with chemotherapy-induced peripheral neuropathy.	Device: Sham Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain as Measured by the Modified Brief Pain Index at 28 Days	To determine the change in pain from day 0 to day 28 (as measured by the Modified Brief Pain Index (BPI), question #3) with scrambler therapy in patients with chemotherapy induced peripheral neuropathy and pain (CIPN). The BPI short form is a pain assessment tool used with cancer patients to measure both severity of pain and interference caused by pain on 0-10 scales with higher scores indicating more pain. A negative score for the change in pain indicates improvement.	Change from baseline to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain at 2 Months as Measured by the Modified Brief Pain Index	To determine the change in pain from day 0 to 2 months (as measured by the Modified Brief Pain Index (BPI), question #3) with scrambler therapy in patients with chemotherapy induced peripheral neuropathy and pain (CIPN). The BPI short form is a pain assessment tool used with cancer patients to measure both severity of pain and interference caused by pain on 0-10 scales with higher scores indicating more pain. A negative score for the change in pain indicates improvement.	Change from baseline to 2 months
Change in Pain at 3 Months as Measured by the Modified Brief Pain Index	To determine the change in pain from day 0 to 3 months (as measured by the Modified Brief Pain Index (BPI), question #3) with scrambler therapy in patients with chemotherapy induced peripheral neuropathy and pain (CIPN). The BPI short form is a pain assessment tool used with cancer patients to measure both severity of pain and interference caused by pain on 0-10 scales with higher scores indicating more pain. A negative score for the change in pain indicates improvement.	Change from baseline to 3 months
Changes in Patient Reported Sensory Outcomes at 28 Days	This was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20, a CIPN-specific questionnaire which includes two scales assessing sensory and motor symptoms and functioning with each question measured on a 0-3 scale. For sensory there are 9 questions with a total score range from 0-27 with higher scores indicating more bothersome symptoms. A negative change in score indicates improvement in symptoms.	Change from baseline to 28 days
Changes in Patient Reported Sensory Outcomes at 2 Months	This was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20, a CIPN-specific questionnaire which includes two scales assessing sensory and motor symptoms and functioning with each question measured on a 0-3 scale. For sensory there are 9 questions with a total score range from 0-27 with higher scores indicating more bothersome symptoms. A negative change in score indicates improvement in symptoms.	Change from baseline to 2 months
Changes in Patient Reported Sensory Outcomes at 3 Months	This was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20, a CIPN-specific questionnaire which includes two scales assessing sensory and motor symptoms and functioning with each question measured on a 0-3 scale. For sensory there are 9 questions with a total score range from 0-27 with higher scores indicating more bothersome symptoms. A negative change in score indicates improvement in symptoms.	Change from baseline to 3 months
Changes in Patient Reported Motor Outcomes at 28 Days	This will be assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20, a CIPN-specific questionnaire which includes two scales assessing sensory and motor symptoms and functioning with each question measured on a 0-3 scale. For motor there are 8 questions with a total score range from 0-24 with higher scores indicating more bothersome symptoms. A negative change in score indicates improvement in symptoms.	Change from baseline to 28 days
Changes in Patient Reported Motor Outcomes at 2 Months	This will be assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20, a CIPN-specific questionnaire which includes two scales assessing sensory and motor symptoms and functioning with each question measured on a 0-3 scale. For motor there are 8 questions with a total score range from 0-24 with higher scores indicating more bothersome symptoms. A negative change in score indicates improvement in symptoms.	Change from baseline to 2 months
Changes in Patient Reported Motor Outcomes at 3 Months	This will be assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CIPN20, a CIPN-specific questionnaire which includes two scales assessing sensory and motor symptoms and functioning with each question measured on a 0-3 scale. For motor there are 8 questions with a total score range from 0-24 with higher scores indicating more bothersome symptoms. A negative change in score indicates improvement in symptoms.	Change from baseline to 3 months
Number of Patients Who Stopped Using Opioids at 28 Days	This will be assessed by concomitant medication review by a study team member during the 10 days of treatment. Follow-up was assessed as participant self-report over the last 10 days; all opiates were further tabulated using a morphine oral dose equivalents table to allow better comparison between patients and arms.	28 days post-intervention
Number of Patients Who Stopped Using Neuroleptics at 28 Days	This will be assessed by concomitant medication review by a study team member during the 10 days of treatment. Follow-up was assessed as participant self-report over the last 10 days; all opiates were further tabulated using a morphine oral dose equivalents table to allow better comparison between patients and arms.	28 days post-intervention

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Thomas J. Smith, MD, FACP, SKCCC at Johns Hopkins

Publications and helpful links

General Publications

• Cathcart-Rake EJ, Hilliker DR, Loprinzi CL. Chemotherapy-induced neuropathy: Central resolution of a peripherally perceived problem? Cancer. 2017 Jun 1;123(11):1898-1900. doi: 10.1002/cncr.30650. Epub 2017 Mar 3. No abstract available.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): March 24, 2017
• Study Completion (Actual): March 24, 2017

Study Registration Dates

• First Submitted: March 23, 2014
• First Submitted That Met QC Criteria: April 8, 2014
• First Posted (Estimate): April 11, 2014

Study Record Updates

• Last Update Posted (Actual): August 17, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Neuropathy; Chemotherapy-induced peripheral neuropathy; Peripheral neuropathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: J1384 (Other Identifier: SKCCC at Johns Hopkins); NA_00086429 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No