Chronic Unexplained Nausea and Vomiting, Gastroparesis
Conditions
Brief summary
The hypothesis of this pilot study is that nVNS will result in relief of nausea by modulation of vagal nerve activity. nVNS is the first non-invasive, handheld medical device applied on the side of the neck and sends gentle, patented mild electrical stimulation through the skin to activate the vagus nerve. nVNS offers a potential alternative to Gastric electrical stimulation (GES) that could eliminate significant risks of injury or illness or identify likely responders to implantable neurostimulator including implanted VNS (iVNS). nVNS could provide a more effective and safer alternative to the use of traditional rescue medications.
Detailed description
The patient will receive the gammaCore (nVNS) device and a video instruction will be use to explain how to properly handle the device. Treatment can only start after eligibility has been fully checked and all data collected at screening have been keyed into the trial database. The patient will be instructed to use the nVNS in place of the rescue medications. When the nauseas gets bad enough that they feel to use a rescue medication they will first use the device on one side of the neck for two 2-minute stimulations and wait fifteen minutes to check if the stimulation works. If this does not help either, they will stimulate with an additional 2 stimulations and wait for another fifteen minutes. If there is no improvement rescue medication will be used. nVNS can be used up to, but no more than, 8 times a day.
Interventions
DEVICEnVNS (gammaCore)
The treatment will be self-administered using nVNS and will be applied for 4 weeks; a member of the study will provide the proper training on the correct use of nVNS. The patient will be instructed to use the nVNS in place of the rescue medications. When the nauseas gets bad enough that they feel to use a rescue medication they will first use the device on one side of the neck for two 2-minute stimulations and wait fifteen minutes to check if the stimulation works. If this does not help either, they will stimulate with an additional 2 stimulations and wait for another fifteen minutes. If there is no improvement rescue medication will be used. nVNS can be used up to, but no more than, 8 times a day.
Sponsors
ElectroCore INC
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older at registration. * Diagnosis of gastroparesis as documented by gastric emptying scintigraphy (4-hour emptying after a low-fat meal with any combination of 2- and 4-hour retention of \>60% and 10%, respectively), or Chronic Unexplained Nausea and Vomiting (CUNV). * Ongoing symptoms (i.e. Nausea and vomiting, bloating, and abdominal pain) with a nausea score of 3 or more on the patient assessment of upper gastrointestinal disorders-symptom severity index (PAGI-SYM) scale at baseline (moderate to severe nausea). * Exclusion of other causes of symptoms such as mechanical gastrointestinal obstruction, uncontrolled esophagitis, peptic ulcer disease, etc. By standard radiographic or endoscopic tests. * Use of the following medications on an as-needed basis: ondansetron, promethazine or prochlorperazine but no more than four times a day.
Exclusion criteria
* Another active disorder, which could explain symptoms in the opinion of the investigator. * Age \< than 18 years. * Pregnancy or nursing. * A previous surgery of the upper gastrointestinal tract, including vagotomy. * Use of narcotics more than 3 days per week. * History of prolonged QT interval or a history of clinically significant arrhythmia. * Abnormal baseline ECG (e.g. Second- and third-degree heart block, atrial fibrillation, atrial flutter, recent history of ventricular tachycardia or ventricular fibrillation, or clinically significant premature ventricular contraction). * Previous bilateral or right cervical vagotomy. * Uncontrolled high blood pressure. * Currently implanted with an electrical and/or neurostimulator device, including but not limited to cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant. * History of carotid endarterectomy or vascular neck surgery on the right side. * Implanted with metal cervical spine hardware or has a metallic implant near the gammaCore stimulation site. * Any other condition, which in the opinion of the investigator would impede compliance or hinder the completion of the study. * Failure to give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Daily Use of Rescue Medications for Exacerbation of Nausea/Vomiting. | Baseline, 4, 6, 10 and 12 weeks of study participation | Average daily use of rescue medications for exacerbation of nausea/vomiting = sum of nausea medications / number of days with non-missing nausea medication data. |
Countries
United States
Participant flow
Pre-assignment details
After meeting the criteria, patients underwent a 7-day screening to establish baseline symptoms and nausea medication intake. Subjects were then randomly assigned to use the nVNS device on one side of the neck for 4 weeks. This was followed by a 2-week washout period before switching to the opposite side, with an additional 2-week washout at the end.
Participants by arm
| Arm | Count |
|---|---|
| nVNS Was First Applied to One Side of the Neck, Followed by Stimulation on the Opposite Side. After meeting the criteria, patients underwent a 7-day screening to establish baseline symptoms and nausea medication intake. Candidates who were eligible after the screening were then randomly assigned to use the nVNS (gammaCore) device on one side of the neck for 4 weeks, followed by a 2-week washout period before switching to the opposite side, with an additional 2-week washout at the end. Eight subjects were excluded before starting nVNS due to missing baseline information on symptoms and nausea medication intake.
The treatment with nVNS will be self-administered for 4 weeks, with proper training provided by a study member on the correct use of the device. Patients will be instructed to use nVNS instead of rescue medications. When nausea becomes severe, patients will first apply two 2-minute stimulations on one side of the neck and wait 15 minutes to assess its effectiveness. If the nausea persists, they will apply an additional two stimulations and wait another 15 minutes. If there is still no improvement, they may use rescue medication. nVNS can be used up to 8 times per day, but no more. | 49 |
| Total | 49 |
Baseline characteristics
| Characteristic | nVNS Was First Applied to One Side of the Neck, Followed by Stimulation on the Opposite Side. |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants |
| Age, Continuous | 34 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 44 Participants |
| Region of Enrollment United States | 49 Participants |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 1 / 41 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Average Daily Use of Rescue Medications for Exacerbation of Nausea/Vomiting.
Average daily use of rescue medications for exacerbation of nausea/vomiting = sum of nausea medications / number of days with non-missing nausea medication data.
Time frame: Baseline, 4, 6, 10 and 12 weeks of study participation
Population: The analysis included only participants who completed each study intervention.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| nVNS Was First Applied to One Side of the Neck, Followed by Stimulation on the Opposite Side. | Average Daily Use of Rescue Medications for Exacerbation of Nausea/Vomiting. | Final Wash Out (12 Weeks Follow-up) | 0.537 medications/day |
| nVNS Was First Applied to One Side of the Neck, Followed by Stimulation on the Opposite Side. | Average Daily Use of Rescue Medications for Exacerbation of Nausea/Vomiting. | Second Side (10 Weeks Follow-up) | 0.447 medications/day |
| nVNS Was First Applied to One Side of the Neck, Followed by Stimulation on the Opposite Side. | Average Daily Use of Rescue Medications for Exacerbation of Nausea/Vomiting. | Baseline | 1.186 medications/day |
| nVNS Was First Applied to One Side of the Neck, Followed by Stimulation on the Opposite Side. | Average Daily Use of Rescue Medications for Exacerbation of Nausea/Vomiting. | First Side (4 Weeks Follow-up) | 0.551 medications/day |
| nVNS Was First Applied to One Side of the Neck, Followed by Stimulation on the Opposite Side. | Average Daily Use of Rescue Medications for Exacerbation of Nausea/Vomiting. | Wash Out (6 Weeks Follow-up) | 0.754 medications/day |