Neuropathy
Conditions
Keywords
Neuropathy, Peripheral neuropathy, Chemotherapy-induced peripheral neuropathy
Brief summary
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.
Interventions
DEVICEScrambler Therapy
DEVICESham Therapy
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain as Measured by the Modified Brief Pain Index at 28 Days | Change from baseline to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain at 3 Months as Measured by the Modified Brief Pain Index | Change from baseline to 3 months | 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. |
| Changes in Patient Reported Sensory Outcomes at 28 Days | Change from baseline to 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. |
| Changes in Patient Reported Sensory Outcomes at 2 Months | Change from baseline to 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. |
| Changes in Patient Reported Sensory Outcomes at 3 Months | Change from baseline to 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 in Pain at 2 Months as Measured by the Modified Brief Pain Index | Change from baseline to 2 months | 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. |
| Changes in Patient Reported Motor Outcomes at 2 Months | Change from baseline to 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. |
| Changes in Patient Reported Motor Outcomes at 3 Months | Change from baseline to 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. |
| Number of Patients Who Stopped Using Opioids at 28 Days | 28 days post-intervention | 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. |
| Number of Patients Who Stopped Using Neuroleptics at 28 Days | 28 days post-intervention | 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. |
| Changes in Patient Reported Motor Outcomes at 28 Days | Change from baseline to 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. |
Countries
United States
Participant flow
Pre-assignment details
1 participant was consented and enrolled for training purposes only with the scrambler machine. This participant was not randomized into an arm and was not used in analysis.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Scrambler Therapy | 18 |
| 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.
Sham Therapy | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Secondary Outcomes (2 and 3 Month f/u) | Death | 0 | 1 |
| Secondary Outcomes (2 and 3 Month f/u) | Lost to Follow-up | 8 | 6 |
| Treatment and Primary Outcome | Ineligible (not used in analysis) | 1 | 0 |
| Treatment and Primary Outcome | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Sham Therapy | Scrambler Therapy |
|---|---|---|---|
| Age, Continuous | 59.31 years STANDARD_DEVIATION 8.97 | 58.94 years STANDARD_DEVIATION 9.31 | 59.71 years STANDARD_DEVIATION 8.88 |
| Baseline Pain Score | 6.57 units on a scale STANDARD_DEVIATION 1.75 | 6.83 units on a scale STANDARD_DEVIATION 1.62 | 6.29 units on a scale STANDARD_DEVIATION 1.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 18 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Motor subscale score at baseline | 11.2 units on a scale STANDARD_DEVIATION 5.12 | 11.83 units on a scale STANDARD_DEVIATION 5.09 | 10.53 units on a scale STANDARD_DEVIATION 5.21 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 10 Participants | 12 Participants |
| Sensory subscale score at baseline | 14.69 units on a scale STANDARD_DEVIATION 5.19 | 15.83 units on a scale STANDARD_DEVIATION 4.49 | 13.47 units on a scale STANDARD_DEVIATION 5.73 |
| Sex: Female, Male Female | 27 Participants | 15 Participants | 12 Participants |
| Sex: Female, Male Male | 9 Participants | 3 Participants | 6 Participants |
| Using neuroleptics at baseline or during treatment | 7 Participants | 4 Participants | 3 Participants |
| Using opioids at baseline or during treatment | 8 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 1 / 18 |
| other Total, other adverse events | 1 / 18 | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
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.
Time frame: Change from baseline to 28 days
Population: Data was analyzed from 17/18 participants in Arm 1 since one was deemed ineligible in retrospect.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Scrambler Therapy | Change in Pain as Measured by the Modified Brief Pain Index at 28 Days | -0.5 units on a scale | Standard Deviation 1.2 |
| Sham Therapy | Change in Pain as Measured by the Modified Brief Pain Index at 28 Days | -1.06 units on a scale | Standard Deviation 2.32 |
Secondary
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.
Time frame: Change from baseline to 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Scrambler Therapy | Change in Pain at 2 Months as Measured by the Modified Brief Pain Index | -0.31 units on a scale | Standard Deviation 0.8 |
| Sham Therapy | Change in Pain at 2 Months as Measured by the Modified Brief Pain Index | -0.25 units on a scale | Standard Deviation 0.92 |
Secondary
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.
Time frame: Change from baseline to 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Scrambler Therapy | Change in Pain at 3 Months as Measured by the Modified Brief Pain Index | -0.75 units on a scale | Standard Deviation 1.78 |
| Sham Therapy | Change in Pain at 3 Months as Measured by the Modified Brief Pain Index | -0.44 units on a scale | Standard Deviation 1.12 |
Secondary
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.
Time frame: Change from baseline to 28 days
Population: Data was analyzed from 17/18 participants in Arm 1 since one was deemed ineligible in retrospect.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Scrambler Therapy | Changes in Patient Reported Motor Outcomes at 28 Days | -2.97 units on a scale | Standard Deviation 6.49 |
| Sham Therapy | Changes in Patient Reported Motor Outcomes at 28 Days | -2.83 units on a scale | Standard Deviation 6.35 |
Secondary
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.
Time frame: Change from baseline to 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Scrambler Therapy | Changes in Patient Reported Motor Outcomes at 2 Months | -5.88 units on a scale | Standard Deviation 7.27 |
| Sham Therapy | Changes in Patient Reported Motor Outcomes at 2 Months | -5.67 units on a scale | Standard Deviation 6.59 |
Secondary
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.
Time frame: Change from baseline to 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Scrambler Therapy | Changes in Patient Reported Motor Outcomes at 3 Months | -6.62 units on a scale | Standard Deviation 6.59 |
| Sham Therapy | Changes in Patient Reported Motor Outcomes at 3 Months | -8.53 units on a scale | Standard Deviation 7.28 |
Secondary
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.
Time frame: Change from baseline to 28 days
Population: Data was analyzed from 17/18 participants in Arm 1 since one was deemed ineligible in retrospect.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Scrambler Therapy | Changes in Patient Reported Sensory Outcomes at 28 Days | -4.76 units on a scale | Standard Deviation 6.69 |
| Sham Therapy | Changes in Patient Reported Sensory Outcomes at 28 Days | -4.67 units on a scale | Standard Deviation 6.66 |
Secondary
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.
Time frame: Change from baseline to 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Scrambler Therapy | Changes in Patient Reported Sensory Outcomes at 2 Months | -8.94 units on a scale | Standard Deviation 9.33 |
| Sham Therapy | Changes in Patient Reported Sensory Outcomes at 2 Months | -8.39 units on a scale | Standard Deviation 8.37 |
Secondary
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.
Time frame: Change from baseline to 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Scrambler Therapy | Changes in Patient Reported Sensory Outcomes at 3 Months | -9.62 units on a scale | Standard Deviation 9.22 |
| Sham Therapy | Changes in Patient Reported Sensory Outcomes at 3 Months | -11.39 units on a scale | Standard Deviation 7.84 |
Secondary
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.
Time frame: 28 days post-intervention
Population: Data was analyzed from 17/18 participants in Arm 1 since one was deemed ineligible in retrospect.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Scrambler Therapy | Number of Patients Who Stopped Using Neuroleptics at 28 Days | 1 Participants |
| Sham Therapy | Number of Patients Who Stopped Using Neuroleptics at 28 Days | 0 Participants |
Secondary
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.
Time frame: 28 days post-intervention
Population: Data was analyzed from 17/18 participants in Arm 1 since one was deemed ineligible in retrospect.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Scrambler Therapy | Number of Patients Who Stopped Using Opioids at 28 Days | 3 Participants |
| Sham Therapy | Number of Patients Who Stopped Using Opioids at 28 Days | 1 Participants |