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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if stimulating the vagus nerve with the PARASYM TENS unit, a type of neuromodulation therapy, can improve heart health in individuals who have undergone chemotherapy. The focus is on enhancing heart function and reducing blood inflammation. Participants will receive either the actual treatment or a placebo for comparison. Ideal candidates are those treated for breast cancer or lymphoma with anthracycline in the last 30 days and who also have conditions such as high blood pressure, diabetes, or a history of smoking. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could improve heart health after chemotherapy.

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 prior data suggests that this neuromodulation device is safe for improving heart function?

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe for people. Studies have found taVNS to be safe and practical for medical use, as it has been tested and does not cause significant harm. Additionally, vagus nerve stimulation can help reduce inflammation, a process that can lead to pain and other health problems. Overall, the PARASYM TENS unit for nerve stimulation is well-tolerated, with few reported side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the PARASYM TENS unit because it offers a new approach to addressing chemotherapy-related cardiovascular risks. Unlike traditional treatments that typically involve medications or lifestyle changes, this device uses neuromodulation, which involves stimulating nerves to potentially reduce heart-related side effects of chemotherapy. The PARASYM unit is applied to the ear, delivering low-level electrical impulses, which is a non-invasive and targeted method that could offer a safer and more convenient option compared to systemic treatments. This innovative approach could lead to quicker relief and reduce the burden of side effects associated with current therapies.

What evidence suggests that the PARASYM TENS unit is effective for improving heart function and reducing inflammation in chemotherapy patients?

Research shows that gentle stimulation of the vagus nerve, such as that provided by the PARASYM TENS unit, may benefit heart health. Past studies found that this type of stimulation improves heart function and increases heart rate variability. It might also reduce inflammation markers in the blood, often linked to heart stress. Early results from animal studies support these benefits, showing better heart control and slower progression of heart failure. This trial will compare the effects of the PARASYM TENS unit with a placebo version of the device, suggesting that the PARASYM TENS unit might help people at risk of heart problems due to chemotherapy. ^{1 5 6 7 8}

Who Is on the Research Team?

Tarun W. Dasari, MD, MPH

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

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.

Atrial paced rhythm

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05921253

Neuromodulation of Cardiovascular Risks Associated With ... Neuromodulation of Cardiovascular Risks Associated With Cardiotoxic Chemotherapy: A First in Human Randomized Pilot Study. Neuromodulation in Cancer Study (OU- ...

2. withpower.com withpower.com/trial/phase-breast-cancer-6-2023-2d50b?condition=&query=Parasym+Device&overallStatus=Recruiting&hasNoPlacebo=false

Neuromodulation for Chemotherapy-Related Cardiovascular Risks 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 ...

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/407695

Neuromodulation of Cardiovascular Risks Associated With ... This study is to determine if low level vagus nerve stimulation will lead to improvement in heart function, heart rate variation, and in the ...

4. parasym.co parasym.co/scientific-publications.html

The Parasym system - Scientific Publications Chronic vagus nerve stimulation improves autonomic control and attenuates systemic inflammation and heart failure progression in a canine high-rate pacing model ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10514600/

Efficacy of transcutaneous auricular vagus nerve stimulation ... The interventions will last for 7 days, twice daily for 30 min each. The primary efficacy outcome is pain reduction on day 7. The secondary ...

6. parasym.co parasym.co/parasym-device-transcutaneous-vagus-nerve-stimulation.html

The Vagus Nerve Stimulation Devices: Ultimate Health Guide Parasym's Vagus Nerve Stimulation Device, Nurosym, increases Heart Rate Variability ... According to the research findings on the effects of tVNS on cancer ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9772204/

Safety of transcutaneous auricular vagus nerve stimulation ... This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2589537025002779

Efficacy and safety of transcutaneous auricular vagus ... Vagus nerve stimulation (VNS) has been proven to attenuate systemic inflammatory response, which is involved in the pathological processes of neuropathic pain, ...