Neurostimulation for Paroxysmal Sympathetic Hyperactivity
Recruiting in Palo Alto (17 mi)
Overseen byBinod Balakrishnan, MD
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Medical College of Wisconsin
Disqualifiers: Intractable seizures, heart block, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This trial is testing a new device called PENFS, which is worn on the ear and sends electrical signals to help control symptoms in children with severe brain injuries who suffer from PSH. The device aims to calm the overactive nervous system, potentially reducing the need for multiple medications and their side effects.
Will I have to stop taking my current medications?
The trial information does not specify whether participants need to stop taking their current medications. It is best to consult with the trial coordinators for specific guidance.
What data supports the effectiveness of the treatment Percutaneous Electrical Nerve Field Stimulation (PENFS) for Paroxysmal Sympathetic Hyperactivity?
Research on similar treatments, like electrical vagus nerve stimulation, shows promise in managing conditions with autonomic imbalance, such as heart failure, by reducing excessive sympathetic activity. This suggests that PENFS might also help in conditions like Paroxysmal Sympathetic Hyperactivity by modulating nerve activity.
12345Is percutaneous electrical nerve field stimulation (PENFS) safe for humans?
PENFS, used in devices like Neuro-Stim, has been shown to have minimal adverse effects, such as minor bleeding, localized skin irritation, and rare infections at the site of use. It is considered a minimal-risk procedure by several institutions, making it generally safe for human use.
678910How is the treatment for Paroxysmal Sympathetic Hyperactivity using PENFS different from other treatments?
PENFS (Percutaneous Electrical Nerve Field Stimulation) is unique because it is a non-invasive treatment that delivers electrical stimulation to the external ear to modulate central pain pathways, unlike other treatments that may involve drugs or invasive procedures.
611121314Eligibility Criteria
This trial is for children aged 2-17 with moderate to severe PSH due to brain injury, who are not fully conscious (Glasgow Coma Scale < 15). It's not suitable for kids with ear issues, uncontrollable seizures, other implants like pacemakers, or those under 2 years old.Inclusion Criteria
My pain severity is more than moderate.
You have a Glasgow Coma Scale score that is less than 15.
My child is between 2-17 years old and has PSH due to ASBI.
Exclusion Criteria
I have an ear deformity or severe skin irritation on my ear lobes.
I have seizures that medication cannot control.
Known pregnancy
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Application of the PENFS device over the external ear for continuous 120-hour periods
Up to 192 hours
Continuous monitoring during device application
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests a non-drug treatment called PENFS. This device is applied to the ear and may calm overactive nervous systems in kids with PSH by stimulating nerve activity that can relax the body.
1Treatment groups
Experimental Treatment
Group I: Percutaneous Electrical Nerve Field Stimulation (PENFS) device applicationExperimental Treatment1 Intervention
The peripheral neurostimulator, PENFS device, will be placed over the external ear of enrolled patients. The device will continuously stay in place for 120 hours.
PENFS is already approved in United States for the following indications:
🇺🇸 Approved in United States as IB-Stim for:
- Functional abdominal pain associated with irritable bowel syndrome in adolescents 11-18 years of age
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Children's WisconsinMilwaukee, WI
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Who Is Running the Clinical Trial?
Medical College of WisconsinLead Sponsor
Advancing a Healthier Wisconsin Endowment (AHW)Collaborator
Children's WisconsinCollaborator
References
Electrical vagus nerve stimulation for the treatment of chronic heart failure. [2021]Autonomic dysregulation is a feature of chronic heart failure (HF) and is characterized by a sustained increase of sympathetic drive and by withdrawal of parasympathetic activity. Both sympathetic overdrive and increased heart rate are predictors of poor long-term outcome in patients with HF. Pharmacologic agents that partially inhibit sympathetic activity, such as beta-adrenergic receptor blockers, effectively reduce mortality and morbidity in patients with chronic HF. In contrast, modulation of parasympathetic activation as a potential therapy for HF has received only limited attention because of its inherent complex cardiovascular effects. This review examines results of experimental animal studies that provide support for the possible use of electrical vagus nerve stimulation (VNS) as a long-term therapy for the treatment of chronic HF. The review also addresses the effects of VNS on potential modifiers of the HF state, including proinflammatory cytokines, nitric oxide elaboration, and myocardial expression of gap junction proteins. Finally, the safety, feasibility, and efficacy trends of VNS in patients with advanced HF are reviewed.
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."
Low-frequency subthreshold sympathetic stimulation augments maximal reflex parasympathetic salivary secretion in cats. [2018]Electrical stimulation of the peripheral cut end of the cervical sympathetic trunk for 3 min at frequencies
Scalable and reversible axonal neuromodulation of the sympathetic chain for cardiac control. [2023]Maladaptation of the sympathetic nervous system contributes to the progression of cardiovascular disease and risk for sudden cardiac death, the leading cause of mortality worldwide. Axonal modulation therapy (AMT) directed at the paravertebral chain blocks sympathetic efferent outflow to the heart and maybe a promising strategy to mitigate excess disease-associated sympathoexcitation. The present work evaluates AMT, directed at the sympathetic chain, in blocking sympathoexcitation using a porcine model. In anesthetized porcine (n = 14), we applied AMT to the right T1-T2 paravertebral chain and performed electrical stimulation of the distal portion of the right sympathetic chain (RSS). RSS-evoked changes in heart rate, contractility, ventricular activation recovery interval (ARI), and norepinephrine release were examined with and without kilohertz frequency alternating current block (KHFAC). To evaluate efficacy of AMT in the setting of sympathectomy, evaluations were performed in the intact state and repeated after left and bilateral sympathectomy. We found strong correlations between AMT intensity and block of sympathetic stimulation-evoked changes in cardiac electrical and mechanical indices (r = 0.83-0.96, effect size d = 1.9-5.7), as well as evidence of sustainability and memory. AMT significantly reduced RSS-evoked left ventricular interstitial norepinephrine release, as well as coronary sinus norepinephrine levels. Moreover, AMT remained efficacious following removal of the left sympathetic chain, with similar mitigation of evoked cardiac changes and reduction of catecholamine release. With growth of neuromodulation, an on-demand or reactionary system for reversible AMT may have therapeutic potential for cardiovascular disease-associated sympathoexcitation.NEW & NOTEWORTHY Autonomic imbalance and excess sympathetic activity have been implicated in the pathogenesis of cardiovascular disease and are targets for existing medical therapy. Neuromodulation may allow for control of sympathetic projections to the heart in an on-demand and reversible manner. This study provides proof-of-concept evidence that axonal modulation therapy (AMT) blocks sympathoexcitation by defining scalability, sustainability, and memory properties of AMT. Moreover, AMT directly reduces release of myocardial norepinephrine, a mediator of arrhythmias and heart failure.
Device Autonomic Regulation Therapy in Patients with Heart Failure with Reduced Ejection Fraction. [2020]Heart failure with reduced ejection fraction (HFrEF) is a common, incompletely treatable, complex, progressive, and severe medical problem despite guideline-directed medical therapy. HFrEF is associated with sympathetic activation and parasympathetic inhibition; these reflexive processes may ultimately be maladaptive and exacerbate or even perpetuate the problem. Attempts to regulate autonomic tone during HFrEF in animal models and in humans has shown promise with beneficial effects that include improvement in symptoms, mitigation of arrhythmic events, reduction in mortality, and correction in hemodynamics. Several modalities to regulate autonomic tone such as unilateral parasympathetic nerve activation, baroreceptor activation, renal nerve ablation and spinal cord stimulation have been investigated. Although they demonstrated some benefit, the long-term efficacy in HFrEF has not been proven. Considering specific limitations of each modality, to draw definitive conclusions is impossible at this time. Here, we review the present state-of-the-art hiterature? of device of autonomic regulation therapy to affect outcomes in HFrEF.
Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial. [2018]Development of safe and effective therapies for paediatric abdominal pain-related functional gastrointestinal disorders is needed. A non-invasive, US Food and Drug Administration-cleared device (Neuro-Stim, Innovative Health Solutions, IN, USA) delivers percutaneous electrical nerve field stimulation (PENFS) in the external ear to modulate central pain pathways. In this study, we evaluated the efficacy of PENFS in adolescents with abdominal pain-related functional gastrointestinal disorders.
Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous on-off stimulation. Infection is the most serious implantation-associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6 months and depends on surgical skill and experience. The most frequent stimulation-associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non-invasive VNS delivery systems do not require surgery and permit patient-administered stimulation on demand. These non-invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses.
Minimal adverse effects profile following implantation of periauricular percutaneous electrical nerve field stimulators: a retrospective cohort study. [2020]The periauricular percutaneous implantation of the Neuro-Stim System™ family of devices EAD, MFS, and BRIDGE is a procedure involving the use of a non-opiate, neuromodulation analgesic for relieving acute and chronic pain. It has been approved as a minimal-risk procedure by multiple governmental and institutional facilities. This retrospective report of findings will help quantify the incidence of clinically observed bleeding, localized dermatitis, and infections at the implantation sites of the electrode/needle arrays, dermatitis at the site of the generator, and patient syncope. A total of 1,207 devices, each producing up to 16 percutaneous punctures, for a total of 19,312 punctures were monitored for adverse effects, based on retrospective chart audits conducted at six clinical facilities over a 1-year period.
Vagal Neuromodulation in Chronic Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis. [2021]Objectives: The aim of this study was to evaluate the effects of invasive vagal nerve stimulation (VNS) in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF). Background: Heart failure is characterized by autonomic nervous system imbalance and electrical events that can lead to sudden death. The effects of parasympathetic (vagal) stimulation in patients with HF are not well-established. Methods: From May 1994 to July 2020, a systematic review was performed using PubMed, Embase, and Cochrane Library for clinical trials, comparing VNS with medical therapy for the management of chronic HFrEF (EF ≤ 40%). A meta-analysis of several outcomes and adverse effects was completed, and GRADE was used to assess the level of evidence. Results: Four randomized controlled trials (RCT) and three prospective studies, totalizing 1,263 patients were identified; 756 treated with VNS and 507 with medical therapy. RCT data were included in the meta-analysis (fixed-effect distribution). Adverse effects related to VNS were observed in only 11% of patients. VNS was associated with significant improvement (GRADE = High) in the New York Heart Association (NYHA) functional class (OR, 2.72, 95% CI: 2.07-3.57, p < 0.0001), quality of life (MD -14.18, 95% CI: -18.09 to -10.28, p < 0.0001), a 6-min walk test (MD, 55.46, 95% CI: 39.11-71.81, p < 0.0001) and NT-proBNP levels (MD -144.25, 95% CI: -238.31 to -50.18, p = 0.003). There was no difference in mortality (OR, 1.24; 95% CI: 0.82-1.89, p = 0.43). Conclusions: A high grade of evidence demonstrated that vagal nerve stimulation improves NYHA functional class, a 6-min walk test, quality of life, and NT-proBNP levels in patients with chronic HFrEF, with no differences in mortality.
Percutaneous Electrical Nerve Field Stimulation for Drug-Refractory Pediatric Cyclic Vomiting Syndrome. [2023]Cyclic vomiting syndrome (CVS) is a disabling condition frequently refractory to pharmacologic therapy. The aim of this study was to evaluate the effects of noninvasive, auricular percutaneous electrical nerve field stimulation (PENFS) as prophylactic therapy for pediatric CVS.
Peripheral nerve field stimulation for chronic headache: 60 cases and long-term follow-up. [2022]The objective of this study is to evaluate the efficacy of peripheral nerve field stimulation (PNFS) for the treatment of chronic headache conditions.
Stimulation of the sphenopalatine ganglion in intractable cluster headache: expert consensus on patient selection and standards of care. [2022]Chronic cluster headache (CCH) is a debilitating headache disorder with a significant impairment of the patients' lives. Within the past decade, various invasive neuromodulatory approaches have been proposed for the treatment of CCH refractory to standard preventive drug, but only very few randomized controlled studies exist in the field of neuromodulation for the treatment of drug-refractory headaches. Based on the prominent role of the cranial parasympathetic system in acute cluster headache attacks, high-frequency sphenopalatine ganglion (SPG) stimulation has been shown to abort ongoing attacks in some patients in a first small study. As preventive effects of SPG-stimulation have been suggested and the rate of long-term side effects was moderate, SPG stimulation appears to be a promising new treatment strategy.
Peripheral nerve/field stimulation for chronic pain. [2014]Peripheral nerve stimulation and peripheral nerve field stimulation involve the delivery of electrical stimulation using implanted electrodes either over a target nerve or over the painful area with the goal of modulating neuropathic pain. The selection of appropriate candidates for this therapy hinges on skillful application of inclusion and exclusion criteria, psychological screening, and an invasive screening trial. Patients with significant improvement in pain severity and pain-related disability during the trial are considered candidates for implantation of a permanent system. As with other implanted devices for neuromodulation, risks of mechanical failures, infection, and neurologic complications exist.
Efficacy of Auricular Neurostimulation in Adolescents With Irritable Bowel Syndrome in a Randomized, Double-Blind Trial. [2021]Auricular neurostimulation therapy, in which a noninvasive device delivers percutaneous electrical nerve field stimulation (PENFS) to the external ear, is effective in pediatric patients with functional abdominal pain disorders. Preclinical studies showed that PENFS modulates central pain pathways and attenuates visceral hyperalgesia. We evaluated the efficacy of PENFS in adolescents with irritable bowel syndrome (IBS).