Neurostimulation for Autonomic Dysfunction

Recruiting in Palo Alto (17 mi)

Overseen by Katja Karrento, MD

Age: < 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Medical College of Wisconsin

Must not be taking: Antidepressants

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

Disorders of gut-brain interaction (DGBI) affect up to 25% of U.S. children. Patients often suffer from disabling, multisystem comorbidities that suggest a common root (sleep disturbances, fatigue, anxiety, etc). Yet, DGBI are defined and treated based on GI symptom origin (cyclic vomiting, dyspepsia, irritable bowel) rather than underlying pathophysiology. Many patients manifest comorbidities suggesting an underlying autonomic nervous system (ANS) dysregulation (palpitations, dizziness, cognitive dysfunction). Unfortunately, due to common features of anxiety and visceral hyperreactivity and lack of obvious pathology, children with DGBI are frequently diagnosed with psychosomatic or 'benign, functional disorders' and treated with empiric antidepressants despite lack of scientific support and risks of serious side effects. Little is known about the underlying brain-gut mechanisms linking these comorbidities. A lack of targeted treatment options naturally follows the paucity of mechanistic data. A dysregulated ANS response circuit via brainstem nuclei is linked to visceral hypersensitivity. As the team's prior research has shown, ANS regulation can be non-invasively measured via several validated indices of cardiac vagal tone. Using the novel vagal efficiency (VE) metric, the investigators have demonstrated inefficient vagal regulation in cyclic vomiting syndrome and pain-related DGBI and that low VE predicts response to non-invasive, auricular percutaneous electrical nerve field stimulation (PENFS) therapy. PENFS targets brainstem vagal afferent pathways and, along with brain-gut interventions such as hypnotherapy, are the only therapies currently proven effective for pediatric DGBI. Individualizing neurostimulation based on sensory thresholds while assessing dynamic ANS reactivity offers a path towards personalized medicine using the most effective therapies to date. This proposal will test the feasibility of an ANS tracking software in assessing real-time, autonomic regulation and providing individualized neurostimulation in children with nausea/vomiting and ANS imbalance.

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 data supports the effectiveness of the treatment Hypnotherapy and Percutaneous electrical nerve field stimulation for autonomic dysfunction?

Research shows that hypnosis can reduce activity in the sympathetic nervous system (which controls the 'fight or flight' response), which may help treat conditions with strong sympathetic involvement like hypertension and chronic pain. Additionally, neuromodulation therapies have shown promise in restoring autonomic balance in heart failure, suggesting potential benefits for autonomic dysfunction. ^{1 2 3 4 5}

Is neurostimulation generally safe for humans?

Research on neuromodulation treatments like vagus nerve stimulation and other device-based therapies has shown them to be generally safe in humans, although side effects can occur and may be severe in some cases. ^{1 6 7 8 9}

How does hypnotherapy differ from other treatments for autonomic dysfunction?

Hypnotherapy is unique because it uses guided relaxation and focused attention to influence the autonomic nervous system, which is different from other treatments that may involve medications or devices to directly stimulate nerves. This approach is non-invasive and relies on the mind-body connection to potentially improve symptoms. ^{1 2 10 11 12}

Eligibility Criteria

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

I am between 8 and 18 years old.

English speaking

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

Exclusion Criteria

My severe mental health condition is not well-controlled.

I have a diagnosed condition that explains my symptoms.

Implanted electrical device

Trial Timeline

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

Treatment Details

Interventions

• Hypnotherapy (Behavioural Intervention)
• Percutaneous electrical nerve field stimulation (Procedure)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Medical College of Wisconsin Milwaukee, WI

Who Is Running the Clinical Trial?

Medical College of Wisconsin Lead Sponsor

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

References

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

Interventional and device-based autonomic modulation in heart failure. [2015] "Heart failure is an increasingly prevalent disease with high mortality and public health burden. It is associated with autonomic imbalance characterized by sympathetic hyperactivity and parasympathetic hypoactivity. Evolving novel interventional and device-based therapies have sought to restore autonomic balance by neuromodulation. Results of preclinical animal studies and early clinical trials have demonstrated the safety and efficacy of these therapies in heart failure. This article discusses specific neuromodulatory treatment modalities individually-spinal cord stimulation, vagus nerve stimulation, baroreceptor activation therapy, and renal sympathetic nerve denervation."

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

Autonomic stimulation. [2019] Therapeutic stimulation of the autonomic nervous system has been limited by lack of qualitative or quantitative evaluation of autonomic mechanisms. This article provides an historical review of knowledge about autonomic pathways and critical evaluation of available tests of autonomic function. Recent developments in evaluation of autonomic dysfunction and improvement in techniques of neurostimulation have facilitated the development of a number of clinically useful treatments for bladder control, sexual problems, peripheral vascular disease, angina pectoris, and seizure disorders. Future therapeutic measures may allow specific control of hypertension, pain, cardiac arrhythmias, trophic disorders and balance.

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Autonomic Dysfunction in Sleep Disorders: From Neurobiological Basis to Potential Therapeutic Approaches. [2022] Sleep disorder has been portrayed as merely a common dissatisfaction with sleep quality and quantity. However, sleep disorder is actually a medical condition characterized by inconsistent sleep patterns that interfere with emotional dynamics, cognitive functioning, and even physical performance. This is consistent with sleep abnormalities being more common in patients with autonomic dysfunction than in the general population. The autonomic nervous system coordinates various visceral functions ranging from respiration to neuroendocrine secretion in order to maintain homeostasis of the body. Because the cell population and efferent signals involved in autonomic regulation are spatially adjacent to those that regulate the sleep-wake system, sleep architecture and autonomic coordination exert effects on each other, suggesting the presence of a bidirectional relationship in addition to shared pathology. The primary goal of this review is to highlight the bidirectional and shared relationship between sleep and autonomic regulation. It also introduces the effects of autonomic dysfunction on insomnia, breathing disorders, central disorders of hypersomnolence, parasomnias, and movement disorders. This information will assist clinicians in determining how neuromodulation can have the greatest therapeutic effects in patients with sleep disorders.

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

Alterations in electrodermal activity and cardiac parasympathetic tone during hypnosis. [2017] Exploring autonomic nervous system (ANS) changes during hypnosis is critical for understanding the nature and extent of the hypnotic phenomenon and for identifying the mechanisms underlying the effects of hypnosis in different medical conditions. To assess ANS changes during hypnosis, electrodermal activity and pulse rate variability (PRV) were measured in 121 young adults. Participants either received hypnotic induction (hypnosis condition) or listened to music (control condition), and both groups were exposed to test suggestions. Blocks of silence and experimental sound stimuli were presented at baseline, after induction, and after de-induction. Skin conductance level (SCL) and high frequency (HF) power of PRV measured at each phase were compared between groups. Hypnosis decreased SCL compared to the control condition; however, there were no group differences in HF power. Furthermore, hypnotic suggestibility did not moderate ANS changes in the hypnosis group. These findings indicate that hypnosis reduces tonic sympathetic nervous system activity, which might explain why hypnosis is effective in the treatment of disorders with strong sympathetic nervous system involvement, such as rheumatoid arthritis, hot flashes, hypertension, and chronic pain. Further studies with different control conditions are required to examine the specificity of the sympathetic effects of hypnosis.

5. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiac autonomic regulation under hypnosis assessed by heart rate variability: spectral analysis and fractal complexity. [2009] This study examined the effects of hypnosis on autonomic cardiac control. We hypothesized a modification of autonomic modulation of the heart rate with an enhanced vagal tone during hypnosis compared to baseline.

6. Germany pubmed.ncbi.nlm.nih.gov

[Stability of mental stress-induced hemodynamic and autonomic reaction despite successful treatment for psychosomatic disorder]. [2016] Autonomic imbalance and exaggerated stress responses are associated with an increased risk of morbidity and mortality and have been associated with several psychosomatic disorders. Has in-patient psychotherapy any effect on autonomic regulation and mental stress reactivity? In 77 patients undergoing in-patient psychometric treatment psychometric examination and psychophysiological assessment of hemodynamic and autonomic parameters during rest and 2 mental stress tests was performed at the beginning and at the end of in-patient psychotherapy. Despite marked improvements in symptoms our short-term treatment for psychosomatic disorders did not affect autonomic and hemodynamic activation at rest or during stress testing. It remains to be investigated if increased physical activity and relaxation expected after improvement have beneficial physiological effects over longer time spans.

7. Switzerland pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Neuromodulation Treatments in Late-Life Depression. [2022] In this review, the efficacy and safety of FDA approved neuromodulation devices (electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS)), as well as emerging neuromodulation treatments currently under investigation.

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

Vagus nerve stimulation in chronic treatment-resistant depression: preliminary findings of an open-label study. [2019] We evaluated the efficacy and safety of vagus nerve stimulation therapy in the treatment of 11 patients with chronic treatment-resistant depression. Mood was evaluated at frequent intervals over the year following implantation. All measures of depression, including the Hamilton Rating Scale for Depression reduced significantly. The response and remission rates were 55% and 27% respectively at 1 year. Side-effects were common, and some were severe.

9. England pubmed.ncbi.nlm.nih.gov

Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post-traumatic stress disorder. [2021] Patients with post-traumatic stress disorder (PTSD) are at a significantly higher risk of developing hypertension and cardiovascular disease. The mechanisms underlying this increased risk are not known. Studies have suggested that PTSD patients have an overactive sympathetic nervous system (SNS) that could contribute to cardiovascular risk; however, sympathetic function has not previously been rigorously evaluated in PTSD patients. Using direct measurements of sympathetic nerve activity and pharmacological manipulation of blood pressure, we show that veterans with PTSD have augmented SNS and haemodynamic reactivity during both combat-related and non-combat related mental stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and increased inflammation. Identifying the mechanisms contributing to increased cardiovascular (CV) risk in PTSD will pave the way for developing interventions to improve sympathetic function and reduce CV risk in these patients.

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The effect of phototherapy on psychoautonomic disorders of a neurotic nature]. [2017] Bright white light therapy was applied to 51 patients with syndrome of autonomic dysfunction of neurotic origin (1 hour of light exposure every day in the morning, during 2 weeks, 60 sm from the lamp, 3300 lux). Improvement occurred in 52% of the patients (responders--group 1, nonresponders--2). Changes occurred in nearly all symptoms: neuroendocrine, motivation, psychoautonomic, pain, psychopathologic. After the treatment in group 1 there was an increase of power of EEG spectrum, intensification of manifestations of the slow activity and decrease of the fast one from the two sides, an approach of the coefficient of asymmetry to the control levels as well as elevation of the urine excretion of metabolites of both catecholamines and serotonin. Initially higher power of EEG spectrum in group 2, became still more increased due to intensification of manifestations of theta and beta-2 rhythms from the two sides. Meanwhile coefficient of asymmetry was sharply decreased as well as general secretory activity inhibited. There were such symptoms and indices which had changed either negatively or positively under the influence of phototherapy.

11. England pubmed.ncbi.nlm.nih.gov

Midodrine treatment for chronic fatigue syndrome. [2019] The long term results of midodrine treatment in a patient having debilitating chronic fatigue syndrome (CFS) are reported. Midodrine treatment, directed at the autonomic nervous system, resulted in correction of the dysautonomia followed by improvement of fatigue. This finding is consistent with the hypothesis that dysautonomia plays a major part in the pathophysiology of CFS and that therapies directed at the autonomic nervous system may be effective in the treatment of CFS.

12. New Zealand 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. [2022] Noninvasive brain stimulation technique is an interesting tool to investigate the causal relation between cortical functioning and autonomic nervous system (ANS) responses.