Neurostimulation for Autonomic Dysfunction

Overseen By Mychoua Vang, BS

Age: < 65

Sex: Female

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Must not be taking: Antidepressants

Disqualifiers: Organic disease, Parenteral nutrition, Developmental delays, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores treatments for children experiencing nausea, vomiting, and autonomic nervous system (ANS) issues, which can cause symptoms like dizziness, fatigue, and sleep problems. Researchers are testing a nerve stimulation therapy, known as percutaneous electrical nerve field stimulation (PENFS), that targets brain pathways to manage these symptoms, either alone or with hypnotherapy. The goal is to determine if personalized treatment based on ANS responses can improve symptoms. Children aged 11-18 who have experienced symptoms like dizziness or fatigue for at least three months may be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could lead to new treatment options for children with similar symptoms.

Do I need to stop my current medications for the trial?

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.

What prior data suggests that this neurostimulation technique is safe for children with autonomic dysfunction?

A previous study found that percutaneous electrical nerve field stimulation (PENFS) showed no serious side effects, indicating it is generally well-tolerated. Patients using PENFS for abdominal pain experienced positive results without major issues.

Research has also studied hypnotherapy for its effects on the autonomic nervous system, which controls automatic functions like heartbeat. It has proven effective in treating conditions related to this system, such as chronic pain, with no significant safety concerns reported.

Both treatments appear safe based on current research, offering promising options for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they offer a novel approach to managing autonomic dysfunction. Unlike traditional treatments that may focus on medications or lifestyle changes, the percutaneous electrical nerve field stimulation (PENFS) therapy uses electrical pulses to stimulate nerves and potentially improve autonomic function. When combined with hypnotherapy, this approach could harness both physical and mental pathways to enhance treatment outcomes. This dual method is particularly intriguing as it might provide faster and more comprehensive relief for patients, tapping into both the body's and mind's healing capabilities.

What evidence suggests that this trial's treatments could be effective for disorders of gut-brain interaction?

This trial will evaluate the effectiveness of percutaneous electrical nerve field stimulation (PENFS) and hypnotherapy for autonomic dysfunction. Studies have shown that PENFS can alleviate abdominal pain-related issues in teenagers by improving vagus nerve function, which controls automatic body functions like heart rate and digestion. Many gut-related disorders are believed to be linked to problems with these automatic functions. In this trial, one group will receive PENFS therapy alone, while another will receive PENFS therapy combined with hypnotherapy. Research suggests that hypnotherapy can also help manage these automatic functions, making it useful for conditions like chronic pain and anxiety. Both treatments show promise for addressing the root causes of gut-related disorders, not just the symptoms. ^{1 2 3 6 7}

Who Is on the Research Team?

Katja Karrento, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for children with gut-brain interaction disorders like cyclic vomiting, dyspepsia, and irritable bowel syndrome. These conditions often come with other issues such as sleep disturbances, fatigue, and anxiety due to autonomic nervous system (ANS) dysregulation. Children who are frequently misdiagnosed or treated with antidepressants without clear benefits may benefit from this study.

Inclusion Criteria

English speaking

I have been diagnosed with cyclic vomiting syndrome or functional dyspepsia and agree to join the study.

I have had symptoms like dizziness, fainting, and fatigue for at least 3 months.

Exclusion Criteria

My severe mental health condition is not well-controlled.

I have a diagnosed condition that explains my symptoms.

Implanted electrical device

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive personalized PENFS therapy for 6 weeks, with weekly autonomic nervous system assessments. Some participants also receive adjunctive hypnotherapy.

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hypnotherapy
• Percutaneous electrical nerve field stimulation

Trial Overview

The trial is testing the use of hypnotherapy and percutaneous electrical nerve field stimulation (PENFS) to treat disorders related to gut-brain interactions in children. It aims to personalize neurostimulation based on individual sensory thresholds while tracking real-time ANS reactivity using new software.

How Is the Trial Designed?

Group I: PENFS (percutaneous electrical nerve field stimulation) therapy Experimental Treatment 1 Intervention

Personalized PENFS therapy x 6 weeks based on weekly autonomic nervous system assessments

Group II: PENFS (percutaneous electrical nerve field stimulation) therapy + Hypnotherapy Active Control 2 Interventions

Personalized PENFS therapy x 6 weeks based on weekly autonomic nervous system assessments + adjuntive hypnotherapy

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Recent advancements in evaluating autonomic dysfunction and neurostimulation techniques have led to effective treatments for various conditions, including bladder control issues, sexual dysfunction, and angina.

Future therapies may enable targeted control of conditions like hypertension, pain, and cardiac arrhythmias, highlighting the potential for more precise autonomic nervous system interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autonomic stimulation. Upton, AR., White, AM.[2019]

In a study involving 50 healthy subjects, including 21 older adults over 60, anodal transcranial direct current stimulation (tDCS) was found to significantly improve cardiovascular function by enhancing vagal activity and reducing sympathetic activity during stimulation.

The results indicate that tDCS can positively influence heart health in older adults by improving temporal ventricular repolarization dispersion and increasing baroreflex sensitivity, suggesting a potential therapeutic role for tDCS in managing autonomic nervous system responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years. Piccirillo, G., Ottaviani, C., Fiorucci, C., et al.[2022]

In a study of 121 young adults, hypnosis was found to significantly decrease skin conductance level (SCL), indicating reduced sympathetic nervous system activity compared to a control group listening to music.

These results suggest that hypnosis may be beneficial for treating conditions linked to high sympathetic activity, such as chronic pain and hypertension, although further research is needed to clarify the specific effects of hypnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in electrodermal activity and cardiac parasympathetic tone during hypnosis. Kekecs, Z., Szekely, A., Varga, K.[2017]

In a study of 11 patients with chronic treatment-resistant depression, vagus nerve stimulation therapy led to significant reductions in depression scores over one year, with response and remission rates of 55% and 27%, respectively.

While the therapy showed promise in improving mood, it was associated with common and sometimes severe side effects, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in chronic treatment-resistant depression: preliminary findings of an open-label study. Corcoran, CD., Thomas, P., Phillips, J., et al.[2019]

Electroconvulsive therapy (ECT) is considered the gold standard for treating treatment-resistant depression (TRD), despite potential cognitive and cardiovascular side effects, and it remains stigmatized.

Transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS) are effective for late-life depression, with TMS having fewer side effects, but VNS shows limited data in older patients; emerging treatments like magnetic seizure therapy and deep brain stimulation show promise but require more safety and efficacy evidence in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Neuromodulation Treatments in Late-Life Depression. van Rooij, SJH., Riva-Posse, P., McDonald, WM.[2022]

In a study of 12 healthy subjects, hypnosis significantly enhanced parasympathetic modulation of heart rate, indicated by increased high-frequency heart rate variability (HFnu) and decreased low-frequency heart rate variability (LFnu), suggesting improved autonomic cardiac control.

Despite these changes in autonomic modulation, the overall heart rate remained unchanged during hypnosis, indicating that hypnosis alters the balance of sympathetic and parasympathetic activity without affecting heart rate directly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac autonomic regulation under hypnosis assessed by heart rate variability: spectral analysis and fractal complexity. Aubert, AE., Verheyden, B., Beckers, F., et al.[2009]

Neuromodulation therapies, such as spinal cord stimulation and vagus nerve stimulation, have shown promise in restoring autonomic balance in heart failure patients, which is crucial given the disease's association with sympathetic hyperactivity and parasympathetic hypoactivity.

Preclinical studies and early clinical trials indicate that these neuromodulatory treatments are both safe and effective, offering new hope for managing heart failure, a condition with high mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventional and device-based autonomic modulation in heart failure. Shen, MJ., Zipes, DP.[2015]

Bright white light therapy was effective in improving symptoms for 52% of the 51 patients with autonomic dysfunction, showing benefits across various symptoms including neuroendocrine and psychological aspects after 2 weeks of treatment.

The therapy led to significant changes in EEG activity and increased urinary excretion of catecholamine and serotonin metabolites in responders, indicating potential mechanisms of action related to brain activity and neurotransmitter regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of phototherapy on psychoautonomic disorders of a neurotic nature]. Solov'eva, AD., Fishman, EIa.[2017]

Sleep disorders are not just about poor sleep quality; they are medical conditions that can significantly affect emotional, cognitive, and physical health, particularly in patients with autonomic dysfunction.

There is a bidirectional relationship between sleep architecture and autonomic regulation, meaning that issues in one can impact the other, which suggests that targeted neuromodulation could be an effective treatment strategy for various sleep disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autonomic Dysfunction in Sleep Disorders: From Neurobiological Basis to Potential Therapeutic Approaches. Kim, H., Jung, HR., Kim, JB., et al.[2022]

In a study of 77 patients undergoing in-patient psychotherapy for psychosomatic disorders, significant symptom improvements were observed, but there was no change in autonomic regulation or hemodynamic responses during rest or mental stress tests.

The findings suggest that while psychotherapy may alleviate symptoms, its short-term effects do not translate to improved autonomic function, indicating that further research is needed to explore the long-term benefits of increased physical activity and relaxation following treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stability of mental stress-induced hemodynamic and autonomic reaction despite successful treatment for psychosomatic disorder]. Lomb, J., Kleiber, C., Herrmann-Lingen, C.[2016]

Veterans with post-traumatic stress disorder (PTSD) exhibit significantly heightened sympathetic nervous system activity and cardiovascular responses during mental stress, which may increase their risk for hypertension and cardiovascular disease.

The study found that PTSD patients have impaired baroreflex sensitivity and elevated inflammation levels, suggesting that these factors contribute to their increased cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post-traumatic stress disorder. Park, J., Marvar, PJ., Liao, P., et al.[2021]

Midodrine treatment, which targets the autonomic nervous system, successfully corrected dysautonomia in a patient with chronic fatigue syndrome (CFS), leading to significant improvement in fatigue levels.

These results support the idea that dysautonomia is a key factor in CFS and suggest that therapies aimed at the autonomic nervous system could be beneficial for treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midodrine treatment for chronic fatigue syndrome. Naschitz, J., Dreyfuss, D., Yeshurun, D., et al.[2019]

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Study Details | NCT00061009 | Hypnosis in Autonomic ...

This study will investigate the relationship between susceptibility to hypnosis and regulation of the autonomic nervous system (nerves that control ...