Pain, Peripheral Neuropathy, Tingling
Conditions
Brief summary
This randomized clinical trial studies how well MC5-A scrambler therapy or transcutaneous electrical nerve stimulation (TENS) therapy work in treating patients with chemotherapy-induced peripheral neuropathy (a nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body). MC5-A scrambler therapy is a type of treatment for nerve pain that uses electrodes placed on the skin, where electricity is carried from the electrodes through the skin and blocks the pain. TENS is a procedure in which mild electric currents are applied to some areas of the skin. It is not yet known whether TENS therapy is more effective than MC5-A scrambler therapy in treating chemotherapy-induced peripheral neuropathy.
Detailed description
PRIMARY OBJECTIVES: I. Evaluate the efficacy of scrambler therapy (MC5-A scrambler therapy) compared to TENS therapy for pain and/or tingling related to chemotherapy-induced peripheral neuropathy (CIPN). II. Evaluate the tolerability of scrambler therapy and compare it to TENS therapy, in this population. III. Evaluate whether scrambler therapy, compared to TENS therapy, can decrease the use of pain medication for CIPN. IV. Explore whether messenger ribonucleic acid (mRNA) gene expression before and after scrambler therapy shows similar findings to what Starkweather et al observed. V. Utilizing high-field magnetic resonance imaging (MRI), to define alterations in functional differences (using resting state blood-oxygen-level dependent \[BOLD\] measures to measure differences in functional connectivity) in treated with the scrambler device in the setting of chemotherapy induced peripheral neuropathy pain. VI. Explore whether scrambler therapy will alter sensation. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo MC5-A scrambler therapy over 30 minutes for 10 consecutive weekdays. ARM II: Patients undergo TENS therapy over 30 minutes daily for 14 days. Patients in both Arms, may crossover to the opposite Arm for an additional 2 weeks of treatment if they elect. After completion of study treatment, patients are followed up weekly for 8 weeks.
Interventions
OTHERTranscutaneous Electrical Nerve Stimulation
Undergo TENS
OTHERLaboratory Biomarker Analysis
Correlative studies
Undergo Scrambler therapy
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pain or symptoms of CIPN of \>= 3 months duration, for which the patient wants intervention * Note: neurotoxic chemotherapy must have been completed \>= 3 months prior to registration and there must be no further planned neurotoxic chemotherapy for \> 5 months after registration * Patients have to relate that tingling or pain was at least a four out of ten problem =\< 7 days prior to registration, on a 0-10 scale where zero was no problem and ten was the worst possible problem * Note: the patient is expected to have tingling or pain of at least 4/10 at the time of the first treatment * Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 0, 1, or 2 * Life expectancy \>= 6 months * Ability to complete questionnaire(s) by themselves or with assistance * Ability to provide informed written consent * Case review by the study chair, or designate, as a case where treatment should be tried
Exclusion criteria
* Any of the following: * Pregnant women * Nursing women * Women of childbearing potential who are unwilling to employ adequate contraception * Existing operational implantable drug delivery systems, e.g. Medtronic Synchromed * Existing implantable medical electronic devices, life-supporting medical devices, and medical monitoring devices * Note: metal implants for orthopedic repair, e.g. pins, clips, plates, cages, joint replacements are allowed as are central venous access devices * History of myocardial infarction or ischemic heart disease within the past six months * History of epilepsy, brain damage, use of anticonvulsants for seizure prevention, concurrently using ketamine, symptomatic brain metastases * 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 gabapentin or pregabalin and not willing to be weaned off of these medications prior to Scrambler therapy initiation * Note: it is OK to continue these medications in patients who are receiving TENS * History of peripheral neuropathy prior to receiving neurotoxic chemotherapy * Prior treatment with Scrambler therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieve at Least a 50% Reduction in Their Primary Problematic Symptom (Either Pain or Tingling) From Baseline on Day 14 | Baseline to Day 14 | The number of participants who achieve at least a 50% reduction in their primary problematic symptom (either pain or tingling) from baseline on Day 14. The participant specified their primary problematic symptom (either pain or tingling) and primary problematic area (either upper or lower extremity) at registration; the respective items used to measure each symptom are considered for this outcome measure. Pain and tingling are measured using either item #6 (How much tingling have you had in your \[fingers or hands; toes or feet\] on average over the past 24 hours?) or item #9 (How much pain have you had in your \[fingers or hands; toes or feet\] on average over the past 24 hours?). Both items use the same scale: 0=None, 10=As bad as can be, with higher scores indicating worse outcome on either the Patient Questionnaire: Before Each Treatment for Upper Extremity Neuropathy or Patient Questionnaire: Before Each Treatment for Lower Extremity Neuropathy at baseline and Day 14. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Indicating Yes, No, or Unsure for Therapy Recommendation to Other Patients With Similar Problems on the Subjective Global Impression of Change Instrument | At 10 weeks | The number of participants indicating 'Yes' for 'Therapy recommendation to other patients with similar problems' on the Subjective Global Impression of Change (SGIC) instrument. The SGIC questionnaire is used to assess the change in quality of life. |
| Change in Sensory, Motor, and Autonomic Neuropathy Subscale Scores From Baseline to Week 10 | Up to 10 weeks | The change in Sensory, Motor, and Autonomic Neuropathy Subscale Scores from Baseline to Week 10 will be derived by subtracting the baseline score from the scores at Week 10. The European Organisation for Research and Treatment of Cancer Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ CIPN-20) Instrument contains 20 items assessing sensory (9 items), motor (8 items), and autonomic symptoms (3 items), using a 4-point Likert scale (1 = not at all, 2 = a little, 3 = quite a bit, and 4 = very much). The range of change in subscale scores is -3 to 3. With a total range for sensory being -27 to 27 and motor being -24 to 24 and autonomic being -9 to 9. With negatives meaning a decrease in neuropathy and positive being an increase. |
| Number of Participants Using Acetaminophen as Pain Medication | Up to 10 weeks | The number of participants using acetaminophen as pain medication is reported below. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Functional MRI (fMRI) | Baseline to up to 10 weeks | Changes in fMRI following Scrambler therapy will be described in the subset of patients selected for this component of the study. |
| Change in Sensation | Baseline to up to 10 weeks | Descriptive statistics will be used for the data from Quantitative Sensory Testing. |
| Change in mRNA Gene Expression | Baseline to up to 10 weeks | In a descriptive manner, the gene expression will be compared to what was previously reported by Starkweather et al. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (MC5-A Scrambler Therapy) Patients undergo MC5-A scrambler therapy over 30 minutes for 10 consecutive weekdays. | 25 |
| Arm II (TENS Therapy) Patients undergo TENS therapy over 30 minutes daily for 14 days. | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal After Beginning Treatment | 0 | 3 |
| Overall Study | Withdrawal Prior to Beginning Treatment | 1 | 0 |
Baseline characteristics
| Characteristic | Arm I (MC5-A Scrambler Therapy) | Arm II (TENS Therapy) | Total |
|---|---|---|---|
| Age, Continuous | 61.0 years | 61.0 years | 61.0 years |
| ECOG Performance Status 0 | 15 Participants | 14 Participants | 29 Participants |
| ECOG Performance Status 1 | 9 Participants | 10 Participants | 19 Participants |
| ECOG Performance Status 2 | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 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 | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 21 Participants | 24 Participants | 45 Participants |
| Sex: Female, Male Female | 17 Participants | 17 Participants | 34 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 25 |
| other Total, other adverse events | 0 / 24 | 1 / 25 |
| serious Total, serious adverse events | 0 / 24 | 0 / 25 |
Outcome results
Primary
Number of Participants Who Achieve at Least a 50% Reduction in Their Primary Problematic Symptom (Either Pain or Tingling) From Baseline on Day 14
The number of participants who achieve at least a 50% reduction in their primary problematic symptom (either pain or tingling) from baseline on Day 14. The participant specified their primary problematic symptom (either pain or tingling) and primary problematic area (either upper or lower extremity) at registration; the respective items used to measure each symptom are considered for this outcome measure. Pain and tingling are measured using either item #6 (How much tingling have you had in your \[fingers or hands; toes or feet\] on average over the past 24 hours?) or item #9 (How much pain have you had in your \[fingers or hands; toes or feet\] on average over the past 24 hours?). Both items use the same scale: 0=None, 10=As bad as can be, with higher scores indicating worse outcome on either the Patient Questionnaire: Before Each Treatment for Upper Extremity Neuropathy or Patient Questionnaire: Before Each Treatment for Lower Extremity Neuropathy at baseline and Day 14.
Time frame: Baseline to Day 14
Population: All Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (MC5-A Scrambler Therapy) | Number of Participants Who Achieve at Least a 50% Reduction in Their Primary Problematic Symptom (Either Pain or Tingling) From Baseline on Day 14 | 10 Participants |
| Arm II (TENS Therapy) | Number of Participants Who Achieve at Least a 50% Reduction in Their Primary Problematic Symptom (Either Pain or Tingling) From Baseline on Day 14 | 5 Participants |
p-value: 0.1228Chi-squared
Secondary
Change in Sensory, Motor, and Autonomic Neuropathy Subscale Scores From Baseline to Week 10
The change in Sensory, Motor, and Autonomic Neuropathy Subscale Scores from Baseline to Week 10 will be derived by subtracting the baseline score from the scores at Week 10. The European Organisation for Research and Treatment of Cancer Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ CIPN-20) Instrument contains 20 items assessing sensory (9 items), motor (8 items), and autonomic symptoms (3 items), using a 4-point Likert scale (1 = not at all, 2 = a little, 3 = quite a bit, and 4 = very much). The range of change in subscale scores is -3 to 3. With a total range for sensory being -27 to 27 and motor being -24 to 24 and autonomic being -9 to 9. With negatives meaning a decrease in neuropathy and positive being an increase.
Time frame: Up to 10 weeks
Population: Participants who completed all subscale items from the EORTC QLQ CIPN-20 at baseline and Week 10 are included in this analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm I (MC5-A Scrambler Therapy) | Change in Sensory, Motor, and Autonomic Neuropathy Subscale Scores From Baseline to Week 10 | Sensory Subscale | -0.4 score on a scale |
| Arm I (MC5-A Scrambler Therapy) | Change in Sensory, Motor, and Autonomic Neuropathy Subscale Scores From Baseline to Week 10 | Motor Subscale | -0.1 score on a scale |
| Arm I (MC5-A Scrambler Therapy) | Change in Sensory, Motor, and Autonomic Neuropathy Subscale Scores From Baseline to Week 10 | Autonomic Subscale | 0.0 score on a scale |
| Arm II (TENS Therapy) | Change in Sensory, Motor, and Autonomic Neuropathy Subscale Scores From Baseline to Week 10 | Autonomic Subscale | 0.0 score on a scale |
| Arm II (TENS Therapy) | Change in Sensory, Motor, and Autonomic Neuropathy Subscale Scores From Baseline to Week 10 | Sensory Subscale | -0.6 score on a scale |
| Arm II (TENS Therapy) | Change in Sensory, Motor, and Autonomic Neuropathy Subscale Scores From Baseline to Week 10 | Motor Subscale | -0.3 score on a scale |
Comparison: Sensory Subscalep-value: 0.79Wilcoxon (Mann-Whitney)
Comparison: Motor Subscalep-value: 0.43Wilcoxon (Mann-Whitney)
Comparison: Autonomic Subscalep-value: 0.97Wilcoxon (Mann-Whitney)
Secondary
Number of Participants Indicating Yes, No, or Unsure for Therapy Recommendation to Other Patients With Similar Problems on the Subjective Global Impression of Change Instrument
The number of participants indicating 'Yes' for 'Therapy recommendation to other patients with similar problems' on the Subjective Global Impression of Change (SGIC) instrument. The SGIC questionnaire is used to assess the change in quality of life.
Time frame: At 10 weeks
Population: Participants who completed the SGIC 'Therapy recommendation to other patients with similar problems' item at Week 10 are included in this analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (MC5-A Scrambler Therapy) | Number of Participants Indicating Yes, No, or Unsure for Therapy Recommendation to Other Patients With Similar Problems on the Subjective Global Impression of Change Instrument | Yes | 16 Participants |
| Arm I (MC5-A Scrambler Therapy) | Number of Participants Indicating Yes, No, or Unsure for Therapy Recommendation to Other Patients With Similar Problems on the Subjective Global Impression of Change Instrument | No | 0 Participants |
| Arm I (MC5-A Scrambler Therapy) | Number of Participants Indicating Yes, No, or Unsure for Therapy Recommendation to Other Patients With Similar Problems on the Subjective Global Impression of Change Instrument | Unsure | 5 Participants |
| Arm II (TENS Therapy) | Number of Participants Indicating Yes, No, or Unsure for Therapy Recommendation to Other Patients With Similar Problems on the Subjective Global Impression of Change Instrument | Yes | 7 Participants |
| Arm II (TENS Therapy) | Number of Participants Indicating Yes, No, or Unsure for Therapy Recommendation to Other Patients With Similar Problems on the Subjective Global Impression of Change Instrument | No | 7 Participants |
| Arm II (TENS Therapy) | Number of Participants Indicating Yes, No, or Unsure for Therapy Recommendation to Other Patients With Similar Problems on the Subjective Global Impression of Change Instrument | Unsure | 3 Participants |
p-value: 0.004Fisher Exact
Secondary
Number of Participants Using Acetaminophen as Pain Medication
The number of participants using acetaminophen as pain medication is reported below.
Time frame: Up to 10 weeks
Population: All Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (MC5-A Scrambler Therapy) | Number of Participants Using Acetaminophen as Pain Medication | 8 Participants |
| Arm II (TENS Therapy) | Number of Participants Using Acetaminophen as Pain Medication | 9 Participants |
Other Pre-specified
Change in Functional MRI (fMRI)
Changes in fMRI following Scrambler therapy will be described in the subset of patients selected for this component of the study.
Time frame: Baseline to up to 10 weeks
Other Pre-specified
Change in mRNA Gene Expression
In a descriptive manner, the gene expression will be compared to what was previously reported by Starkweather et al.
Time frame: Baseline to up to 10 weeks
Other Pre-specified
Change in Sensation
Descriptive statistics will be used for the data from Quantitative Sensory Testing.
Time frame: Baseline to up to 10 weeks