Percutaneous Neurostimulation to Treat Paroxysmal Sympathetic Hyperactivity in Children

NCT05343988 | Terminated FDA Device

• 1 other identifier: 1817951
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Survivors of severe brain injury, such as lack of oxygen or severe traumatic brain injury, frequently experience Paroxysmal Sympathetic Hyperactivity (PSH). PSH is characterized by disabling symptoms such as a fast heart rate, high blood pressure, rapid breathing, rigidity, tremors, and sweating due to uncontrolled sympathetic hyperactivity in the nervous system. Effective treatment is necessary to decrease secondary brain injury, prevent weight loss from increased metabolic demand and reduce suffering. Currently, a combination of medications to slow down the sympathetic nervous system, muscle relaxants, anti-anxiety drugs, gabapentin, and narcotics are used to treat PSH. The sudden, recurrent attacks of PSH often require repeated rescue medications and multiple drugs with a high risk of side effects. Non-drug treatments for PSH may revolutionize treatment. The novel and non-invasive Percutaneous Electrical Nerve Field Stimulation (PENFS) device is an attractive and potentially effective treatment option for PSH. PENFS, applied to the external ear, has been shown to be effective for conditions such as abdominal pain, narcotic withdrawal, and cyclic vomiting syndrome, all which have similar symptoms to PSH. Therefore, the hypothesis is PENFS could be effective in the treatment of PSH. The electrical current delivered by the PENFS device is thought to increase parasympathetic activity by stimulating a branch of the vagus nerve. PENFS was shown to decrease central sympathetic nervous system activity by 36% within 5 minutes of being placed in the ear of a rat model. Similar central inhibition could improve symptoms of PSH. This pilot study aims to evaluate the feasibility of performing an efficacy trial of PENFS for children with PSH.

Conditions

Paroxysmal Sympathetic Hyperactivity

Keywords

peripheral neurostimulator; pediatric; acute severe brain injury

Outcome Measures

Primary Outcomes (4)

• The number of children enrolled (Ages 2-17) with acute severe brain injury (ASBI) and Paroxysmal Sympathetic Hyperactivity (PSH) to use the Percutaneous Electrical Nerve Field Stimulation (PENFS) device for treatment

  Number of patients enrolled

  Up to 192 hours.

• Study retention for those children enrolled with acute severe brain injury (ASBI) and Paroxysmal Sympathetic Hyperactivity (PSH) to use the Percutaneous Electrical Nerve Field Stimulation (PENFS) device for treatment

  Percentage of patients who complete the study

  Up to 192 hours.

• Device tolerability for those children enrolled with acute severe brain injury (ASBI) and Paroxysmal Sympathetic Hyperactivity (PSH) to use the Percutaneous Electrical Nerve Field Stimulation (PENFS) device for treatment

  Percentage of patients withdrawn due to device intolerability

  Up to 192 hours.

• Capturing at least 80 percent of scoring events to assess pediatric Paroxysmal Sympathetic Hyperactivity (PSH) symptoms using the Clinical Feature Severity (CFS) scoring tool

  The CFS will be administered by trained bedside nurses to capture PSH severity in enrolled patients before, during and after initiation of PENFS device treatment. The CFS is a composite measure of Heart Rate, Respiratory Rate, Systolic Blood Pressure, Temperature, Sweating and Posturing. The Scoring is as follows: 0 Nil; 1-6 Mild; 7-12 Moderate; and \>=13 Severe. Percentage of CFS scores collected.

  Up to 192 hours.

Secondary Outcomes (12)

• The change from baseline of the Clinical Feature Scale (CFS) measured throughout the study to 192 hours after device placement

  0 hours before device placement, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 84 hours, 96 hours, 108 hours,120 hours-device discontinuation, 132 hours, 144 hours, 156 hours, 168 hours, 180 hours, 192 hours

• Measure a change in maintenance and rescue medication use for treatment of PSH

  0-24hours, 25-48hours, 49-72hours, 73-96hours, 97-120hours

• Measure pupil size (mm) to determine the change in autonomic response

  -12 hours (12 hours before placement), Time 12 hours (12 hours after placement)

• Measure pupil's constriction velocity (mm/sec) to determine the change in autonomic response

  -12 hours (12 hours before placement), Time 12 hours (12 hours after placement)

• Measure the pupil's dilation velocity (mm/sec) to determine the change in autonomic response

  -12 hours (12 hours before placement), Time 12 hours (12 hours after placement)

Study Arms (1)

Percutaneous Electrical Nerve Field Stimulation (PENFS) device application

EXPERIMENTAL

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.

Device: Percutaneous Electrical Nerve Field Stimulation (PENFS) device application

Interventions

Percutaneous Electrical Nerve Field Stimulation (PENFS) device application DEVICE

PENFS device will be used to treat children with paroxysmal sympathetic hyperactivity (PSH) due to acute severe brain injury.

Also known as: Peripheral neurostimulator

Percutaneous Electrical Nerve Field Stimulation (PENFS) device application

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children 2-17 years age with PSH due to ASBI
• PSH severity score \> 6 (moderate severity)
• Glasgow Coma Scale \< 15

You may not qualify if:

• age \< 2 years (small ears thus less surface area to apply the leads)
• ear deformity or severe dermatitis of ear lobes,
• intractable seizures, heart block, patients with other implantable devices (cardiac pacemaker, vagal nerve stimulator, etc.
• known pregnancy

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Children's Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (18)

• Fernandez-Ortega JF, Prieto-Palomino MA, Munoz-Lopez A, Lebron-Gallardo M, Cabrera-Ortiz H, Quesada-Garcia G. Prognostic influence and computed tomography findings in dysautonomic crises after traumatic brain injury. J Trauma. 2006 Nov;61(5):1129-33. doi: 10.1097/01.ta.0000197634.83217.80.

  PMID: 17099518 BACKGROUND

• Baguley IJ, Slewa-Younan S, Heriseanu RE, Nott MT, Mudaliar Y, Nayyar V. The incidence of dysautonomia and its relationship with autonomic arousal following traumatic brain injury. Brain Inj. 2007 Oct;21(11):1175-81. doi: 10.1080/02699050701687375.

  PMID: 17952716 BACKGROUND

• Rabinstein AA. Paroxysmal sympathetic hyperactivity in the neurological intensive care unit. Neurol Res. 2007 Oct;29(7):680-2. doi: 10.1179/016164107X240071.

  PMID: 18173907 BACKGROUND

• Kirk KA, Shoykhet M, Jeong JH, Tyler-Kabara EC, Henderson MJ, Bell MJ, Fink EL. Dysautonomia after pediatric brain injury. Dev Med Child Neurol. 2012 Aug;54(8):759-64. doi: 10.1111/j.1469-8749.2012.04322.x. Epub 2012 Jun 19.

  PMID: 22712762 BACKGROUND

• Fernandez-Ortega JF, Prieto-Palomino MA, Garcia-Caballero M, Galeas-Lopez JL, Quesada-Garcia G, Baguley IJ. Paroxysmal sympathetic hyperactivity after traumatic brain injury: clinical and prognostic implications. J Neurotrauma. 2012 May 1;29(7):1364-70. doi: 10.1089/neu.2011.2033. Epub 2012 Feb 22.

  PMID: 22150061 BACKGROUND

• Baguley IJ, Nicholls JL, Felmingham KL, Crooks J, Gurka JA, Wade LD. Dysautonomia after traumatic brain injury: a forgotten syndrome? J Neurol Neurosurg Psychiatry. 1999 Jul;67(1):39-43. doi: 10.1136/jnnp.67.1.39.

  PMID: 10369820 BACKGROUND

• Baguley IJ, Heriseanu RE, Cameron ID, Nott MT, Slewa-Younan S. A critical review of the pathophysiology of dysautonomia following traumatic brain injury. Neurocrit Care. 2008;8(2):293-300. doi: 10.1007/s12028-007-9021-3.

  PMID: 17968518 BACKGROUND

• Mehta NM, Bechard LJ, Leavitt K, Duggan C. Severe weight loss and hypermetabolic paroxysmal dysautonomia following hypoxic ischemic brain injury: the role of indirect calorimetry in the intensive care unit. JPEN J Parenter Enteral Nutr. 2008 May-Jun;32(3):281-4. doi: 10.1177/0148607108316196.

  PMID: 18443140 BACKGROUND

• Rabinstein AA, Benarroch EE. Treatment of paroxysmal sympathetic hyperactivity. Curr Treat Options Neurol. 2008 Mar;10(2):151-7. doi: 10.1007/s11940-008-0016-y.

  PMID: 18334137 BACKGROUND

• Baguley IJ, Heriseanu RE, Felmingham KL, Cameron ID. Dysautonomia and heart rate variability following severe traumatic brain injury. Brain Inj. 2006 Apr;20(4):437-44. doi: 10.1080/02699050600664715.

  PMID: 16716989 BACKGROUND

• Phillips SS, Mueller CM, Nogueira RG, Khalifa YM. A Systematic Review Assessing the Current State of Automated Pupillometry in the NeuroICU. Neurocrit Care. 2019 Aug;31(1):142-161. doi: 10.1007/s12028-018-0645-2.

  PMID: 30484008 BACKGROUND

• Miranda A, Taca A. Neuromodulation with percutaneous electrical nerve field stimulation is associated with reduction in signs and symptoms of opioid withdrawal: a multisite, retrospective assessment. Am J Drug Alcohol Abuse. 2018;44(1):56-63. doi: 10.1080/00952990.2017.1295459. Epub 2017 Mar 16.

  PMID: 28301217 BACKGROUND

• Mahadi KM, Lall VK, Deuchars SA, Deuchars J. Cardiovascular autonomic effects of transcutaneous auricular nerve stimulation via the tragus in the rat involve spinal cervical sensory afferent pathways. Brain Stimul. 2019 Sep-Oct;12(5):1151-1158. doi: 10.1016/j.brs.2019.05.002. Epub 2019 May 6.

  PMID: 31129152 BACKGROUND

• Baguley IJ, Perkes IE, Fernandez-Ortega JF, Rabinstein AA, Dolce G, Hendricks HT; Consensus Working Group. Paroxysmal sympathetic hyperactivity after acquired brain injury: consensus on conceptual definition, nomenclature, and diagnostic criteria. J Neurotrauma. 2014 Sep 1;31(17):1515-20. doi: 10.1089/neu.2013.3301. Epub 2014 Jul 28.

  PMID: 24731076 RESULT

• Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available.

  PMID: 8598068 RESULT

• Kim SW, Jeon HR, Kim JY, Kim Y. Heart Rate Variability Among Children With Acquired Brain Injury. Ann Rehabil Med. 2017 Dec;41(6):951-960. doi: 10.5535/arm.2017.41.6.951. Epub 2017 Dec 28.

  PMID: 29354571 RESULT

• Venkata Sivakumar A, Kalburgi-Narayana M, Kuppusamy M, Ramaswamy P, Bachali S. Computerized dynamic pupillometry as a screening tool for evaluation of autonomic activity. Neurophysiol Clin. 2020 Oct;50(5):321-329. doi: 10.1016/j.neucli.2020.09.004. Epub 2020 Oct 11.

  PMID: 33051091 RESULT

• Pozzi M, Locatelli F, Galbiati S, Radice S, Clementi E, Strazzer S. Clinical scales for paroxysmal sympathetic hyperactivity in pediatric patients. J Neurotrauma. 2014 Nov 15;31(22):1897-8. doi: 10.1089/neu.2014.3540. Epub 2014 Sep 26. No abstract available.

  PMID: 24964056 RESULT

Study Officials

• Binod Balakrishnan, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Prospective unblinded pilot study to evaluate the feasibility of use of a peripheral neurostimulator for treatment of paroxysmal sympathetic hyperactivity in children with acute severe brain injury

Study Record Dates

• First Submitted: April 10, 2022
• First Posted: April 25, 2022
• Study Start: September 22, 2022
• Primary Completion: November 30, 2025
• Study Completion: November 30, 2025
• Last Updated: May 1, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After the publication of results - for up to 3 years
• Access Criteria: De-identified, individual participant data including a data dictionary will be made available through encrypted e-mail immediately after publication for 3 years. Researchers who provide a proposal, directed to jbergholte@mcw.edu, will be required to enter into a Data Use Agreement with the Medical College of Wisconsin and demonstrate in a written statement how the data relates to the proposal's objectives. In addition, the Study Protocol, Informed Consent, Statistical Analysis Plan and Clinical Study Report will be made available.

Locations

US (1)