MC5-A Scrambler Therapy or TENS Therapy in Treating Patients With Chemotherapy-Induced Peripheral Neuropathy

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02722434
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 50
• Location: 1
• Arms: 2
• Actual Duration (Months): 64.4
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pain; Peripheral Neuropathy; Tingling	Other: Laboratory Biomarker Analysis; Other: MC5-A Scrambler Therapy; Other: Questionnaire Administration; Other: Transcutaneous Electrical Nerve Stimulation	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. 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).

2. Evaluate the tolerability of scrambler therapy and compare it to TENS therapy, in this population.

3. Evaluate whether scrambler therapy, compared to TENS therapy, can decrease the use of pain medication for CIPN.

4. Explore whether messenger ribonucleic acid (mRNA) gene expression before and after scrambler therapy shows similar findings to what Starkweather et al observed.

5. 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.

6. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: MC15C1 Randomized Scrambler Therapy vs TENS for the Treatment of Chemotherapy-Induced Peripheral Neuropathy
• Actual Study Start Date: Apr 13, 2016
• Actual Primary Completion Date: Sep 1, 2017
• Actual Study Completion Date: Aug 26, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (MC5-A scrambler therapy) Patients undergo MC5-A scrambler therapy over 30 minutes for 10 consecutive weekdays.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: MC5-A Scrambler Therapy; Undergo Scrambler therapy; Other Names: Scrambler Therapy ; Other: Questionnaire Administration; Ancillary studies
Active Comparator: Arm II (TENS therapy) Patients undergo TENS therapy over 30 minutes daily for 14 days.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Other: Transcutaneous Electrical Nerve Stimulation; Undergo TENS; Other Names: TENS transcutaneous electric nerve stimulation

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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.

2. 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.

3. Change in Sensation [Baseline to up to 10 weeks]

   Descriptive statistics will be used for the data from Quantitative Sensory Testing.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Charles Loprinzi, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 12, 2016

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02722434
• Other Study ID Numbers: MC15C1; NCI-2016-00368; MC15C1; P30CA015083
• First Posted: Mar 30, 2016
• Last Update Posted: Jan 12, 2022
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Peripheral Nervous System Diseases

Study Results

Participant Flow

Arm/Group Title	Arm I (MC5-A Scrambler Therapy)	Arm II (TENS Therapy)
Arm/Group Description	Patients undergo MC5-A scrambler therapy over 30 minutes for 10 consecutive weekdays.	Patients undergo TENS therapy over 30 minutes daily for 14 days.
Period Title: Overall Study
STARTED	25	25
Started Treatment	24	25
COMPLETED	24	22
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Arm I (MC5-A Scrambler Therapy)	Arm II (TENS Therapy)	Total
Arm/Group Description	Patients undergo MC5-A scrambler therapy over 30 minutes for 10 consecutive weekdays.	Patients undergo TENS therapy over 30 minutes daily for 14 days.	Total of all reporting groups
Overall Participants	25	25	50
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61.0	61.0	61.0
Sex: Female, Male (Count of Participants)
Female	17 68%	17 68%	34 68%
Male	8 32%	8 32%	16 32%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 4%	1 2%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 12%	0 0%	3 6%
White	21 84%	24 96%	45 90%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 4%	0 0%	1 2%
ECOG Performance Status (Count of Participants)
0	15 60%	14 56%	29 58%
1	9 36%	10 40%	19 38%
2	1 4%	1 4%	2 4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Achieve at Least a 50% Reduction in Their Primary Problematic Symptom (Either Pain or Tingling) From Baseline on Day 14
Description	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

Outcome Measure Data

Analysis Population Description

All Participants

Arm/Group Title	Arm I (MC5-A Scrambler Therapy)	Arm II (TENS Therapy)
Arm/Group Description	Patients undergo MC5-A scrambler therapy over 30 minutes for 10 consecutive weekdays.	Patients undergo TENS therapy over 30 minutes daily for 14 days.
Measure Participants	25	25
Count of Participants [Participants]	10 40%	5 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (MC5-A Scrambler Therapy), Arm II (TENS Therapy)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1228
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Participants who completed the SGIC 'Therapy recommendation to other patients with similar problems' item at Week 10 are included in this analysis.

Arm/Group Title	Arm I (MC5-A Scrambler Therapy)	Arm II (TENS Therapy)
Arm/Group Description	Patients undergo MC5-A scrambler therapy over 30 minutes for 10 consecutive weekdays.	Patients undergo TENS therapy over 30 minutes daily for 14 days.
Measure Participants	21	17
Yes	16 64%	7 28%
No	0 0%	7 28%
Unsure	5 20%	3 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (MC5-A Scrambler Therapy), Arm II (TENS Therapy)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Change in Sensory, Motor, and Autonomic Neuropathy Subscale Scores From Baseline to Week 10
Description	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

Outcome Measure Data

Analysis Population Description

Participants who completed all subscale items from the EORTC QLQ CIPN-20 at baseline and Week 10 are included in this analysis.

Arm/Group Title	Arm I (MC5-A Scrambler Therapy)	Arm II (TENS Therapy)
Arm/Group Description	Patients undergo MC5-A scrambler therapy over 30 minutes for 10 consecutive weekdays.	Patients undergo TENS therapy over 30 minutes daily for 14 days.
Measure Participants	25	25
Sensory Subscale	-0.4	-0.6
Motor Subscale	-0.1	-0.3
Autonomic Subscale	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (MC5-A Scrambler Therapy), Arm II (TENS Therapy)
	Comments	Sensory Subscale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I (MC5-A Scrambler Therapy), Arm II (TENS Therapy)
	Comments	Motor Subscale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm I (MC5-A Scrambler Therapy), Arm II (TENS Therapy)
	Comments	Autonomic Subscale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.97
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Number of Participants Using Acetaminophen as Pain Medication
Description	The number of participants using acetaminophen as pain medication is reported below.
Time Frame	Up to 10 weeks

Outcome Measure Data

Analysis Population Description

All Participants

Arm/Group Title	Arm I (MC5-A Scrambler Therapy)	Arm II (TENS Therapy)
Arm/Group Description	Patients undergo MC5-A scrambler therapy over 30 minutes for 10 consecutive weekdays.	Patients undergo TENS therapy over 30 minutes daily for 14 days.
Measure Participants	25	25
Count of Participants [Participants]	8 32%	9 36%

5. Other Pre-specified Outcome

Title	Change in mRNA Gene Expression
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Change in Functional MRI (fMRI)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Change in Sensation
Description	Descriptive statistics will be used for the data from Quantitative Sensory Testing.
Time Frame	Baseline to up to 10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to 10 weeks
Adverse Event Reporting Description	Participants who completed the study and did not withdraw prior to starting treatment are evaluable for adverse events.
Arm/Group Title	Arm I (MC5-A Scrambler Therapy)		Arm II (TENS Therapy)
Arm/Group Description	Patients undergo MC5-A scrambler therapy over 30 minutes for 10 consecutive weekdays.		Patients undergo TENS therapy over 30 minutes daily for 14 days.
All Cause Mortality
	Arm I (MC5-A Scrambler Therapy)		Arm II (TENS Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/25 (0%)
Serious Adverse Events
	Arm I (MC5-A Scrambler Therapy)		Arm II (TENS Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (MC5-A Scrambler Therapy)		Arm II (TENS Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		1/25 (4%)
Injury, poisoning and procedural complications
Fracture	0/24 (0%)	0	1/25 (4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.