Auricular Neurostimulation for Cyclic Vomiting Syndrome

• ClinicalTrials.gov Identifier: NCT03434652
• Recruitment Status: Recruiting
• First Posted: February 15, 2018
• Last Update Posted: February 11, 2020
• Sponsor: Medical College of Wisconsin
• Information provided by (Responsible Party): Katja Kovacic, Medical College of Wisconsin

Study Description

Brief Summary:

This study evaluates the efficacy of auricular neurostimulation via an non-invasive percutaneous electrical nerve field stimulator in children and adults with cyclic vomiting syndrome.

Condition or disease	Intervention/treatment	Phase
Cyclic Vomiting Syndrome; Abdominal Migraine	Device: Percutaneous neurostimulation	Not Applicable

Detailed Description:

Cyclic vomiting syndrome (CVS) is an difficult to treat and debilitating functional gastrointestinal disorder. Majority of children and adults with CVS have concurrent severe abdominal pain and migraine-features, rendering them incapacitated during the vomiting cycle.

The vagus nerve carries signals of nausea, vomiting and pain between the brain and the gastrointestinal tract and is part of the autonomic nervous system. The autonomic nervous system appears to be in imbalance in patients with CVS during a vomiting cycle. By stimulating a branch of the vagus nerve in the outer ear, this study aims to improve symptoms and quality of life in both children and adults with CVS.

Subjects will be randomized to receive active vs sham (non-active) neurostimulation therapy for 5 days at the onset of a CVS cycle. They will then cross over to the other group (active vs sham) at the onset of the next CVS cycle. Subjects in a separate sub-study receive 6 weeks of active neurostimulation therapy (5 days/week). Pain, nausea, vomiting, anxiety, quality of life, potential side effects and overall symptom improvement will be monitored before and after therapy for the entire study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Each subject randomized to active vs sham therapy, then cross over to the other during next illness cycle
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Auricular Neurostimulation for Children and Adults With Cyclic Vomiting Syndrome: a Pilot Study
• Actual Study Start Date: January 31, 2018
• Estimated Primary Completion Date: August 30, 2020
• Estimated Study Completion Date: August 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Active percutaneous neurostimulation; Subject randomized to 5 days of active vs sham neurostimulation therapy during an illness cycle. With next illness cycle, each subject will cross over to the other one (active vs sham).	Device: Percutaneous neurostimulation; Auricular percutaneous neurostimulation; Other Name: Neuro-Stim System (NSS)-2 BRIDGE
Sham Comparator: Sham percutaneous neurostimulation; Each subject randomized to 5 days of active vs sham neurostimulation therapy during an illness cycle. With next illness cycle, each subject will cross over to the other one (active vs sham).	Device: Percutaneous neurostimulation; Auricular percutaneous neurostimulation; Other Name: Neuro-Stim System (NSS)-2 BRIDGE

Outcome Measures

Primary Outcome Measures :

1. Baxter Retching Faces Scale [ Time Frame: From date of baseline assessment (therapy start date) through next 7 days for each cycle of therapy. Also assessed at follow-up visit 3 months after end of therapy and further follow-up visits up to 12 months after end of therapy. ]
   Daily nausea severity assessed by pictorial nausea faces scale 0-10 (0=no nausea; 10=worse possible nausea) with higher scores indicating worse outcomes (greater nausea).

Secondary Outcome Measures :

1. Numeric pain scale [ Time Frame: From date of baseline assessment (therapy start date) through next 7 days for each cycle of therapy. Also assessed at follow-up visit 3 months after end of therapy and further follow-up visits up to 12 months after end of therapy. ]
   Daily pain severity assessed by numeric pain scale 0-10 (0=no pain; 10=worst possible pain) with higher scores indicating worse outcome (greater pain).
2. Anxiety [ Time Frame: From date of baseline assessment (therapy start date) and day 5 of therapy for each cycle of therapy. Also assessed at follow-up visit 3 months after end of therapy and further follow-up visits up to 12 months after end of therapy. ]
   State-Trait Anxiety Inventory for Children and Adults
3. Health-Related Quality of Life [ Time Frame: From date of baseline assessment (therapy start date) and day 5 of therapy for each cycle of therapy. Also assessed at follow-up visit 3 months after end of therapy and further follow-up visits up to 12 months after end of therapy. ]
   Patient Reported Outcomes Measurement Information Systems
4. Disability in Children [ Time Frame: From date of baseline assessment (therapy start date) and day 5 of therapy for each cycle of therapy. Also assessed at follow-up visit 3 months after end of therapy and further follow-up visits up to 12 months after end of therapy. ]
   Functional Disability Inventory
5. Disability in Adults [ Time Frame: From date of baseline assessment (therapy start date) and day 5 of therapy for each cycle of therapy. Also assessed at follow-up visit 3 months after end of therapy and further follow-up visits up to 12 months after end of therapy. ]
   Sheehan Disability Scale assessing disability and impairment on a scale 0-10 with higher scores indicating more disability. Three sub scales: 1) school/work, 2) social life and 3) family life are assessed (scale 0-10) with a total score reflecting the sum of the 3 subscales (total score range 0-30 with higher score indicating more disability).
6. Global symptoms [ Time Frame: From date of baseline assessment (therapy start date) and day 5 of therapy for each cycle of therapy. Also assessed at follow-up visit 3 months after end of therapy and further follow-up visits up to 12 months after end of therapy. ]
   Global symptom improvement scale

Eligibility Criteria

• Ages Eligible for Study: 8 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Meeting Rome IV Pediatric or Adult criteria for Cyclic Vomiting Syndrome (CVS)
• Concurrent abdominal pain with CVS cycle
• English-speaking
• Lack of other explanation for symptoms
• Either predictable, 'calendar-timed' episodes or prodromal symptoms for 12-24 hours that are predictive of episodes onset

Exclusion Criteria:

• Medically complex and/or suffering from medical condition that may explain symptoms
• Taking a medication that may explain symptoms
• Significant developmental delays
• Patients treated with a new drug affecting the central nervous system within one week of enrollment
• Infection or severe dermatological condition of ear
• Stable vital signs
• No currently implanted electrical device
• For adults (and adolescents as applicable): pregnancy, severe cardiopulmonary disease, concurrent chronic marijuana use (>2 times/month over past 6 months prior to enrollment)

Contacts and Locations

Contacts

Contact: Louis Pawela, BS; 414-266-6728; lpawela@mcw.edu

Locations

United States, Wisconsin

Children's Hospital of Wisconsin; Recruiting

Milwaukee, Wisconsin, United States, 53226

Contact: Lisa Nielson, MS

Contact: Betsy Flinn, BS

Principal Investigator: Katja Kovacic, MD

Sponsors and Collaborators

Medical College of Wisconsin

Investigators

• Principal Investigator: Katja Kovacic, MD; Medical College of Wisconsin

More Information

Publications:

Kovacic K, Hainsworth K, Sood M, Chelimsky G, Unteutsch R, Nugent M, Simpson P, Miranda A. Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18.

Babygirija R, Sood M, Kannampalli P, Sengupta JN, Miranda A. Percutaneous electrical nerve field stimulation modulates central pain pathways and attenuates post-inflammatory visceral and somatic hyperalgesia in rats. Neuroscience. 2017 Jul 25;356:11-21. doi: 10.1016/j.neuroscience.2017.05.012. Epub 2017 May 17.

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. Erratum in: Am J Drug Alcohol Abuse. 2018;44(4):498.

Roberts A, Sithole A, Sedghi M, Walker CA, Quinn TM. Minimal adverse effects profile following implantation of periauricular percutaneous electrical nerve field stimulators: a retrospective cohort study. Med Devices (Auckl). 2016 Nov 3;9:389-393. eCollection 2016.

• Responsible Party: Katja Kovacic, Assistant Professor of Pediatrics, Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT03434652
• Other Study ID Numbers: 1102505-4
• First Posted: February 15, 2018
• Last Update Posted: February 11, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Migraine Disorders; Syndrome; Vomiting; Disease; Pathologic Processes; Signs and Symptoms, Digestive; Signs and Symptoms; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases