Neuromodulation for Chemotherapy-Related Cardiovascular Risks

(OU-SCC-NCAN Trial)

Recruiting at 1 trial location

Overseen By Ingrid Block

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Oklahoma

Disqualifiers: Seizure treatment, Liver disease, Kidney disease, others

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

104 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment PARASYM TENS unit for chemotherapy-related cardiovascular risks?

Research shows that transcutaneous vagus nerve stimulation (tVNS), a component of the PARASYM TENS unit, can improve heart function in cases of heart damage caused by chemotherapy drugs like doxorubicin. Additionally, similar nerve stimulation techniques have been found to help with heart failure by balancing the nervous system. ^{1 2 3 4 5}

Is transcutaneous vagus nerve stimulation (tVNS) safe for humans?

Non-invasive vagus nerve stimulation (VNS), like transcutaneous vagus nerve stimulation (tVNS), is generally considered safe and does not require surgery. It allows for patient-administered stimulation and has improved safety and tolerability compared to older, surgically implanted devices. ^{3 6 7 8 9}

How is the PARASYM TENS unit treatment different from other treatments for chemotherapy-related cardiovascular risks?

The PARASYM TENS unit is unique because it uses non-invasive transcutaneous vagus nerve stimulation (tVNS), which is a safe, portable, and non-surgical method to potentially protect the heart from damage caused by chemotherapy drugs like doxorubicin. Unlike traditional treatments that might involve medication or surgery, this device allows for easy, patient-administered therapy without the need for surgical implantation. ^{2 6 8 10 11}

What is the purpose of this trial?

This study is to determine if low level vagus nerve stimulation will lead to improvement in heart function, heart rate variation, and in the levels of certain chemical markers of inflammation in study participants' blood.

Research Team

Tarun W. Dasari, MD, MPH

Principal Investigator

University of Oklahoma

Eligibility Criteria

This trial is for individuals with breast cancer or lymphoma who have had chest radiation, type 2 diabetes, high blood pressure, are current smokers, obese (BMI ≥ 30), or have a history of heart attack or heart disease. It's not suitable for those who don't meet these conditions.

Inclusion Criteria

I am over 50, had specific cancer treatments, and have at least one health condition like diabetes or heart disease.

Exclusion Criteria

I have end-stage liver or kidney disease.

I have a history of fainting due to sudden drops in heart rate and blood pressure.

I am currently being treated for seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants use a handheld electrical unit for vagus nerve stimulation for 1 hour every day for 14 days

2 weeks

Daily self-administration at home

Follow-up

Participants are monitored for changes in heart function and chemical markers of inflammation

2 weeks

1 visit (in-person) for follow-up assessments

Treatment Details

Interventions

• PARASYM TENS unit
• PARASYM TENS unit (Placebo)

Trial Overview The study tests if a PARASYM neuromodulation device can improve heart function and variability as well as reduce inflammation markers in the blood when used by patients undergoing cardiotoxic chemotherapy.

Participant Groups

Group I: Self administration of LLTS Experimental Treatment 1 Intervention

PARASYM neuromodulation device will be placed in a pre-determined position (different from that of the placebo) of one ear for 1 hour every day for 14 days.

Group II: Self administration of Low Level Tragus Stimulation (LLTS; Placebo) Placebo Group 1 Intervention

PARASYM neuromodulation device will be placed in a pre-determined position of one ear for 1 hour every day for 14 days.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Findings from Research

In a study involving 42 gynecologic oncology patients undergoing cisplatin-based chemotherapy, the ReliefBand, a miniaturized TENS unit, was found to be an effective adjunct to standard antiemetic therapy, particularly in reducing the severity of nausea during the first few days of treatment.

While the overall percentage of patients experiencing absent or minimal nausea was similar between the active and placebo groups, those using the ReliefBand reported significantly lower severity of nausea on days 2 to 4, indicating its potential benefit in managing chemotherapy-induced nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous electrical nerve stimulation as an adjunct for controlling chemotherapy-induced nausea and vomiting in gynecologic oncology patients. Pearl, ML., Fischer, M., McCauley, DL., et al.[2019]

Transcutaneous vagal nerve stimulation (tVNS) significantly improved heart function and reduced cardiac damage in rats treated with the chemotherapy drug doxorubicin (DOX), suggesting it may protect against DOX-induced cardiotoxicity.

tVNS appears to work by rebalancing the autonomic nervous system and reducing inflammation, as it decreased markers of oxidative stress and immune response, indicating a potential new strategy for preventing heart damage during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive transcutaneous vagal nerve stimulation improves myocardial performance in doxorubicin-induced cardiotoxicity. Lai, Y., Zhou, X., Guo, F., et al.[2022]

A single-arm study involving 29 patients demonstrated that transcutaneous electrical nerve stimulation (TENS) is feasible and acceptable for treating chemotherapy-induced peripheral neuropathy (CIPN), with 85% of participants completing the 6-week study.

Participants experienced significant improvements in various symptoms of CIPN, including a 52% reduction in pain and a 30% reduction in tingling, suggesting that TENS could be an effective home-based treatment option for managing CIPN after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wireless transcutaneous electrical nerve stimulation device for chemotherapy-induced peripheral neuropathy: an open-label feasibility study. Gewandter, JS., Chaudari, J., Ibegbu, C., et al.[2021]

Transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) was found to improve heart rate variability in heart failure patients, indicating a better balance in the autonomic nervous system, with significant improvements in rMSSD and SDNN measurements.

The study, involving 43 patients in a double-blind, randomized design, suggests that taVNS is a safe and well-tolerated intervention that may offer therapeutic benefits for heart failure, although further research with larger sample sizes is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular Vagal Neuromodulation and its Application in Patients with Heart Failure and Reduced Ejection Fraction. Couceiro, SM., Sant'Anna, LB., Sant'Anna, MB., et al.[2023]

Vagus nerve stimulation (VNS) applied during ischemia significantly reduces ventricular fibrillation incidence and infarct size by approximately 59%, while improving cardiac function and mitochondrial health, as shown in a study with 28 swine.

VNS is ineffective when applied at the onset of reperfusion, highlighting the critical importance of timing for its cardioprotective effects against ischemic-reperfusion injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation initiated late during ischemia, but not reperfusion, exerts cardioprotection via amelioration of cardiac mitochondrial dysfunction. Shinlapawittayatorn, K., Chinda, K., Palee, S., et al.[2016]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

In a pilot study involving 20 patients with cancer pain, transcutaneous electrical nerve stimulation (TENS) was found to be safe, with 85% of patients using intensity-modulated TENS (IMT) reporting at least slight pain improvement compared to 50% with placebo TENS (PBT).

However, the overall change in average pain intensity did not significantly differ between IMT and PBT, suggesting that while TENS may be desired by patients, it may not provide greater analgesic effects than placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous electrical nerve stimulation for advanced cancer pain inpatients in specialist palliative care-a blinded, randomized, sham-controlled pilot cross-over trial. Siemens, W., Boehlke, C., Bennett, MI., et al.[2021]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

Transcutaneous low-level vagus nerve stimulation (tVNS) in 15 male volunteers showed significant reductions in left ventricular contractility and output, indicating a potential for cardiac autonomic modulation.

While tVNS reduced heart workload, it also led to increased blood pressure and total peripheral resistance, suggesting a reflex response that needs further investigation to understand its therapeutic implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular responses to low-level transcutaneous vagus nerve stimulation. Sinkovec, M., Trobec, R., Meglic, B.[2021]

The AutoStim feature of the Model 106 Vagus Nerve Stimulation (VNS) Therapy System effectively detected and treated seizures in 31 out of 89 instances during a 3-5 day monitoring period, with 61.3% of those seizures ending during stimulation.

After 12 months, patients showed significant improvements in quality of life and seizure severity, with a 50% responder rate, indicating the long-term efficacy and safety of the device in managing drug-resistant partial onset seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance--The U.S. E-37 Trial. Fisher, RS., Afra, P., Macken, M., et al.[2022]

In a study of 67 patients with implanted Vagus Nerve Stimulation (VNS) devices, the AutoStim technology was shown to provide additional stimulations in response to tachycardia, which can help manage treatment-resistant epilepsy.

The research identified that the number of extra stimulations varies with different tachycardia thresholds and duty cycles, providing valuable insights for optimizing VNS settings to enhance patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between duty cycle, tachycardia threshold and autostimulation delivery in cardio-responsive vagus nerve stimulation. Guzner, A., Macken, M.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous electrical nerve stimulation as an adjunct for controlling chemotherapy-induced nausea and vomiting in gynecologic oncology patients. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Non-invasive transcutaneous vagal nerve stimulation improves myocardial performance in doxorubicin-induced cardiotoxicity. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Wireless transcutaneous electrical nerve stimulation device for chemotherapy-induced peripheral neuropathy: an open-label feasibility study. [2021]

4. Brazil pubmed.ncbi.nlm.nih.gov

Auricular Vagal Neuromodulation and its Application in Patients with Heart Failure and Reduced Ejection Fraction. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation initiated late during ischemia, but not reperfusion, exerts cardioprotection via amelioration of cardiac mitochondrial dysfunction. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Transcutaneous electrical nerve stimulation for advanced cancer pain inpatients in specialist palliative care-a blinded, randomized, sham-controlled pilot cross-over trial. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Cardiovascular responses to low-level transcutaneous vagus nerve stimulation. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance--The U.S. E-37 Trial. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

The relationship between duty cycle, tachycardia threshold and autostimulation delivery in cardio-responsive vagus nerve stimulation. [2021]