Effectiveness of Electrical Neurostimulation in Cyclic Vomiting Syndrome.

• ClinicalTrials.gov Identifier: NCT04721171
• Recruitment Status: Terminated
• First Posted: January 22, 2021
• Results First Posted: February 14, 2022
• Last Update Posted: March 4, 2022
• Sponsor: Medical College of Wisconsin
• Information provided by (Responsible Party): Thangam Venkatesan, Medical College of Wisconsin

Study Description

Brief Summary:

We hypothesize that 1) Neurostimulation via a novel auricular percutaneous electrical nerve field stimulation (PENFS) device is a safe, non-invasive opioid-sparing alternative therapy for severe abdominal pain, nausea, and vomiting associated with CVS and will reduce the need for opioids. We also hypothesize that 2) PENFS reduces the length of stay (LOS), and improves patient satisfaction. We propose the following specific aim:

Aim 1. Investigate the efficacy of PENFS compared to a sham in patients with CVS seen in the ED or in the clinic or hospitalized with an acute CVS episode.

Objectives:

1. Demonstrate reduction in abdominal pain, nausea, and vomiting using validated tools.
2. Obviate or reduce the need for opioids.
3. Reduce the length of hospital stay and improve patient satisfaction.

This approach will specifically address the current opioid problem using a novel, non-invasive neurostimulation therapy with proven efficacy for opioid withdrawal. Long-term, it may improve health care outcomes and significantly reduce overall health care costs.

Condition or disease	Intervention/treatment	Phase
Cyclic Vomiting Syndrome	Device: The Bridge device	Not Applicable

Detailed Description:

Opioid use in CVS and the critical need for opioid sparing therapy

Given the lack of knowledge about pathophysiology and evidence-based therapies, patients are often hospitalized to treat symptoms of CVS. During an episode, patients present with severe vomiting and abdominal pain and are treated empirically with IV fluids, antiemetics, benzodiazepines, and opioids. Estimates of opioid use range from 23%-27% in adults with CVS. Patients are often dissatisfied with the level of analgesia as recurrent opioid use results in tolerance and dependence. This often undermines the physician-patient relationship and patients even leave against medical advice out of frustration with what they perceive as ineffective care. This can lead to worse outcomes including recurrent hospitalizations, morbidity and increased health care costs.

Preliminary data from a study by our group reveals that of 101 patients hospitalized with CVS at Froedtert Hospital, chronic opioid therapy is associated with a two-fold increased risk of hospitalization (RR 2.22, CI 1.1-4.4, P=0.02) and three-fold increase in hospital length of stay (LOS) (RR 3.43, CI 1.26-9.34, P=0.01). In a study of 132 CVS patients, opioid use was associated with non-response to amitriptyline (53% vs 15%, p<0.05), a prophylactic therapy used in CVS. This in turn was associated with increased frequency and duration of CVS episodes per year and increased number of hospitalizations/emergency department (ED) visits at baseline (18% vs 15.2%, p<0.05). Hence there is an urgent need for an opioid-sparing, non-invasive strategy to treat CVS symptoms.

In summary, CVS is common and disabling and is associated with significant health care costs. Our proposed project using a novel, non-invasive device to treat CVS will also address the current opioid crisis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: Sham versus real device
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effectiveness of Electrical Neurostimulation as an Opioid-Sparing Alternative in the Treatment of Cyclic Vomiting Syndrome.
• Actual Study Start Date: April 23, 2019
• Actual Primary Completion Date: February 1, 2020
• Actual Study Completion Date: February 9, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Intervention group; The Bridge device is a non-invasive percutaneous electrical nerve field stimulation (PENFS) applied to the external ear. The Bridge device delivers low voltage (3.2), continuous stimulation for 5 days (around the clock) in alternating frequencies (1-10Hz) with an impulse interval of 100ms/2 sec. This is placed on the ear as per standard protocol at the beginning of the study and removed by the patient after 5 days.	Device: The Bridge device; he Bridge device is a non-invasive percutaneous electrical nerve field stimulation (PENFS) applied to the external ear. The Bridge device delivers low voltage (3.2), continuous stimulation for 5 days (around the clock) in alternating frequencies (1-10Hz) with an impulse interval of 100ms/2 sec. This is placed on the ear as per standard protocol at the beginning of the study and removed by the patient after 5 days.
Sham Comparator: Placebo Group; The sham is similar in appearance to the Bridge device but does not deliver any electrical stimulation and is a sham that is designed to look identical to the Bridge device. It is placed on the external ear at the beginning of the study and removed by the patient after 5 days.	Device: The Bridge device; he Bridge device is a non-invasive percutaneous electrical nerve field stimulation (PENFS) applied to the external ear. The Bridge device delivers low voltage (3.2), continuous stimulation for 5 days (around the clock) in alternating frequencies (1-10Hz) with an impulse interval of 100ms/2 sec. This is placed on the ear as per standard protocol at the beginning of the study and removed by the patient after 5 days.

Outcome Measures

Primary Outcome Measures :

1. Change in Severity of Abdominal Pain [ Time Frame: The change in abdominal pain will be measured at baseline (before intervention) and then at 2 hours, 24 hours and at 5 days post intervention. ]
   Abdominal pain will be assessed through Visual Analog Scale with the score of ranging from 0 to 10, with 0 being the least and 10 being the worst pain.
2. Change in Need for Opioids Between Device and Sham [ Time Frame: The dose of opioids use ( morphine equivalent) will be measured at baseline (before intervention) and then at 2 hours, 24 hours and at 5 days post intervention. ]
   The amount of opioids used by the patient will be recorded in all subjects and will be converted into morphine equivalents for comparison

Secondary Outcome Measures :

1. Change in Index for Nausea, Vomiting and Retching (INVR) Scores [ Time Frame: The INVR scores will be assessed be measured at baseline (before intervention) and then at 2 hours, 24 hours and at 5 days post intervention. ]
   The severity of daily nausea, vomiting and retching will be assessed using the Index for Nausea, Vomiting and Retching (INVR). This is a validated tool to measure the severity of nausea, vomiting and retching. The scores range from 0-32 with 0 being the least severe and 32 being the most severe.
2. Length of Stay in the Hospital (LOS) [ Time Frame: LOS will be determined at end of 1 month ]
   Hospital Length of stay (LOS) in days which refers to the no of days that the patient was admitted in the inpatient ward or unit
3. Patient Satisfaction [ Time Frame: Patient satisfaction will be assessed at end of 1 month ]
   A validated patient satisfaction score will be used

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria

• Patients who meet Rome criteria for cyclic vomiting syndrome and are in an acute episode.

Exclusion Criteria:

• Developmental delay
• Non-English speaking patients
• Pregnancy
• Any implanted electrical device
• Any significant dermatological/infectious condition of the ear

Contacts and Locations

Locations

United States, Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Medical College of Wisconsin

Investigators

• Principal Investigator: Thangam Venkatesan; MCW

  Study Documents (Full-Text)

Documents provided by Thangam Venkatesan, Medical College of Wisconsin:

Study Protocol and Statistical Analysis Plan  [PDF] February 18, 2019

More Information

• Responsible Party: Thangam Venkatesan, Professor, Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT04721171
• Other Study ID Numbers: PRO00032752
• First Posted: January 22, 2021
• Results First Posted: February 14, 2022
• Last Update Posted: March 4, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: NA. Our data will only be made available to the study team at the Medical College of Wisconsin as noted in the IRB

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Syndrome; Vomiting; Disease; Pathologic Processes; Signs and Symptoms, Digestive