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Vagal Nerve Stimulation for Gastroparesis (VNS)

Primary Purpose

Gastroparesis

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Vagal Nerve Stimulation
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastroparesis

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Male or female.
  2. Age 21-65 years old.
  3. Established diagnosis of functional dyspepsia, idiopathic or diabetic gastroparesis as per AGA (American Gastroenterology Association) guidelines.
  4. Patient is capable of giving informed consent and undergo upper endoscopy.
  5. Patient is on stable doses of other medications for gastroparesis for preceding 4 weeks prior to enrollment (baseline measures).

Exclusion Criteria

  1. Surgical-related gastroparesis
  2. Extrinsic myopathy or neuropathy causing gastroparesis.
  3. Use of narcotic pain medications in the preceding 2 weeks of study enrollment.
  4. Patients with enteric feeding tubes or requiring parenteral nutrition (Patients with g-tubes who are stable for 3 months and not using the g-tube for venting may be eligible. patient with J-tubes are not eligible.
  5. Patients with severe flare requiring hospitalization.
  6. Untreated significant depression or suicidal thoughts.
  7. Pregnant or breast-feeding women.
  8. History of gastric pacemaker implantation.
  9. Patients with prior gastric surgery, including fundoplication, partial/total gastrectomy, or gastric bypass.
  10. Patients with malabsorption of enteric, pancreatic, or hepatibiliary etiology.
  11. Patients with primary pulmonary disorders that affect the spirulina breath test.
  12. Patients with implantable electronic devices.
  13. Patients with carotid artery atherosclerosis.

Sites / Locations

  • Stanford University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Idiopathic Gastroparesis

Diabetic Gastroparesis

Functional Dyspepsia

Arm Description

Patients with idiopathic gastroparesis and delayed gastric emptying. All patients in trial will be giving themselves vagal nerve stimulation for two minutes on each side twice a day in the morning and the night for four weeks starting at visit 3 and ending at visit 5.

Patients with diabetic gastroparesis and delayed gastric emptying. All patients in trial will be giving themselves vagal nerve stimulation for two minutes on each side twice a day in the morning and the night for four weeks starting at visit 3 and ending at visit 5.

Patients with functional dyspepsia and normal gastric emptying. All patients in trial will be giving themselves vagal nerve stimulation for two minutes on each side twice a day in the morning and the night for four weeks starting at visit 3 and ending at visit 5.

Outcomes

Primary Outcome Measures

Effect of Vagal Nerve Stimulation on Gastroparesis Symptoms as Measures by the Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD) Questionnaire.
Investigators will send daily GCSI-DD to patients for 8 weeks. This 10 item questionnaire measures the severity of gastroparesis symptoms on a scale 0-5. 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=very severe. Investigators hypothesize a change of more than 0.75 points. Scored were recorded daily at each time point and scores then averaged to produce an overall score (range: 0 to 5, higher scores correspond to worse symptoms).
Effect of Vagal Nerve Stimulation on the Gastric Emptying Spirulina Breath Test Emptying Time
Investigators will measure a change in gastric emptying time before and after vagal nerve stimulation as measured in minutes. Higher number (longer times) indicate more severe gastroparesis.

Secondary Outcome Measures

PROMIS Pain Interference Questionnaire Score as a Measure of the Effect of VNS Therapy on Overall Pain
The effect of VNS therapy on overall pain interference as assessed by the PROMIS (Patient Reported Outcomes Measurement Information System) pain interference questionnaire which is a 6 item questionnaire on a 5 point scale to assess the impact of pain on daily life. Scores are summed and converted to percentiles normalized for the population (normalized T-score). 50 indicates the population mean with a standard deviation of 10. The higher the T-score, the more severe the symptoms.
Short Form 12 (SF-12) Score the Effect of VNS Therapy on Overall Wellbeing and Health
The effect of VNS therapy on overall wellbeing and health as assessed by the SF-12. Score range: 0-100, higher scores correspond to better quality of life.
Number of Participants With Any Serious or Treatment-emergent Adverse Event (AE) as a Measure of the Safety and Tolerability of VNS in Patients With Gastroparesis
The safety and tolerability of VNS in patients with gastroparesis assessed by recording any side effects or adverse events. Number of patients reporting serious or treatment related adverse events are reported
Heart Rate Variability (HRV) as a Measure of the Effect of VNS Therapy on Vagal Tone
The effect of VNS therapy on vagal tone as measured bv HRV (accounting for respiratory rate variability) using electrocardiogram (ASNAR) device. HRV is measured as an RFa value, a measure of the high-frequency heart rate (bpm^2 per hertz). Normal RFa is 0.5 to 8.0.
Effect of VNS on Mucosal Inflammation
Median fluorescence intensity (MFI) data were preprocessed for each cytokine through a sequence of averaging over duplicate wells, natural-logarithm transformation to reduce variance heterogeneity, and isolation and removal of plate effects. The effects of VNS therapy on gastric and small intestine inflammation was measured as average fold change across all tissue cytokines from endoscopic mucosal biopsies before and after VNS, using cytokine multiplex assays, which report relative levels of various cytokines as adjusted mean fluorescence intensity (MFI).
The Effect of VNS Therapy on Gastric and Small Intestine Leukocyte Infiltration.
The effects of VNS therapy on gastric and small intestine leukocyte infiltration was measured as relative abundance (normalized ratio) of immune cells (identified via CD45 marker) to total live cells across tissue leukocytes from endoscopic mucosal biopsies before and after VNS, using flow cytometry.

Full Information

First Posted
April 11, 2017
Last Updated
September 7, 2023
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT03120325
Brief Title
Vagal Nerve Stimulation for Gastroparesis
Acronym
VNS
Official Title
Therapeutic Potential and Neuroimmune Mechanisms of Vagal Nerve Stimulation on Gastrointestinal Motility and Inflammation
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Recruitment challenges due to the COVID19 pandemic and funding not available to restart.
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
August 24, 2018 (Actual)
Study Completion Date
August 24, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

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.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is investigating a new form of treatment for a digestive disorder called gastroparesis. Gastroparesis is thought to be caused by a mix of inflammation and neural dysfunction. The vagal nerve is a large nerve originating from the brain that regulates digestive function. Patients with gastroparesis have what is a called a low vagal tone which results in gastrointestinal motility problems and inflammation; therefore, investigators hypothesize that increasing vagal tone through a hand-held vagal nerve simulator will reduce inflammation and gastrointestinal motility problems in gastroparesis patients. Investigators will evaluate this hypothesis through the use of upper endoscopy testing, breath testing, and blood, stool, urine, heart rate variability, and saliva testing before and after 4 weeks of vagal nerve stimulation (VNS) treatment. There are 6 research visits Visit 1 and visit 2 may take up to 8 weeks (screening/baseline) Visit 3 and visit 4 will take 4 weeks (VNS treatment) visit 5 and 6 will take approximately 4 weeks (VNS followup/washout) Consequently, it is possible that if a patient were to be at the farthest ends of visit windows, they could potentially be in the study for approx 16 weeks. Visit 1 and 2 may be less than 8 weeks which would shorten the patient's overall involvement in the study. The treatment phase of the study will always be 4 weeks with an additional 4 week washout phase. Use of the VNS device takes 4 weeks. Endoscopy and blood work are taken before and after the treatment period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastroparesis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
15 participants planned enrollment in each arm: Diabetic Gastroparesis Functional Dyspepsia Idiopathic Gastoparesis
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Idiopathic Gastroparesis
Arm Type
Experimental
Arm Description
Patients with idiopathic gastroparesis and delayed gastric emptying. All patients in trial will be giving themselves vagal nerve stimulation for two minutes on each side twice a day in the morning and the night for four weeks starting at visit 3 and ending at visit 5.
Arm Title
Diabetic Gastroparesis
Arm Type
Experimental
Arm Description
Patients with diabetic gastroparesis and delayed gastric emptying. All patients in trial will be giving themselves vagal nerve stimulation for two minutes on each side twice a day in the morning and the night for four weeks starting at visit 3 and ending at visit 5.
Arm Title
Functional Dyspepsia
Arm Type
Experimental
Arm Description
Patients with functional dyspepsia and normal gastric emptying. All patients in trial will be giving themselves vagal nerve stimulation for two minutes on each side twice a day in the morning and the night for four weeks starting at visit 3 and ending at visit 5.
Intervention Type
Device
Intervention Name(s)
Vagal Nerve Stimulation
Intervention Description
Patients will be giving themselves vagal nerve stimulation for four weeks at interval of two times a day for two minutes on each side for four weeks. The impact of the intervention on gastroparesis symptoms will be measured by upper endoscopy biopsies, blood work, autonomic function tests, survey data, stool samples, urine sample, and saliva samples before after after the four weeks of stimulation treatment.
Primary Outcome Measure Information:
Title
Effect of Vagal Nerve Stimulation on Gastroparesis Symptoms as Measures by the Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD) Questionnaire.
Description
Investigators will send daily GCSI-DD to patients for 8 weeks. This 10 item questionnaire measures the severity of gastroparesis symptoms on a scale 0-5. 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=very severe. Investigators hypothesize a change of more than 0.75 points. Scored were recorded daily at each time point and scores then averaged to produce an overall score (range: 0 to 5, higher scores correspond to worse symptoms).
Time Frame
Baseline (2 weeks prior to initiation), week 4 (7 days), week 8 (7 days)
Title
Effect of Vagal Nerve Stimulation on the Gastric Emptying Spirulina Breath Test Emptying Time
Description
Investigators will measure a change in gastric emptying time before and after vagal nerve stimulation as measured in minutes. Higher number (longer times) indicate more severe gastroparesis.
Time Frame
Baseline and week 4 (3 hours to assess at each time point)
Secondary Outcome Measure Information:
Title
PROMIS Pain Interference Questionnaire Score as a Measure of the Effect of VNS Therapy on Overall Pain
Description
The effect of VNS therapy on overall pain interference as assessed by the PROMIS (Patient Reported Outcomes Measurement Information System) pain interference questionnaire which is a 6 item questionnaire on a 5 point scale to assess the impact of pain on daily life. Scores are summed and converted to percentiles normalized for the population (normalized T-score). 50 indicates the population mean with a standard deviation of 10. The higher the T-score, the more severe the symptoms.
Time Frame
Baseline, week 4, week 8
Title
Short Form 12 (SF-12) Score the Effect of VNS Therapy on Overall Wellbeing and Health
Description
The effect of VNS therapy on overall wellbeing and health as assessed by the SF-12. Score range: 0-100, higher scores correspond to better quality of life.
Time Frame
Baseline, week 4, week 8
Title
Number of Participants With Any Serious or Treatment-emergent Adverse Event (AE) as a Measure of the Safety and Tolerability of VNS in Patients With Gastroparesis
Description
The safety and tolerability of VNS in patients with gastroparesis assessed by recording any side effects or adverse events. Number of patients reporting serious or treatment related adverse events are reported
Time Frame
8 weeks
Title
Heart Rate Variability (HRV) as a Measure of the Effect of VNS Therapy on Vagal Tone
Description
The effect of VNS therapy on vagal tone as measured bv HRV (accounting for respiratory rate variability) using electrocardiogram (ASNAR) device. HRV is measured as an RFa value, a measure of the high-frequency heart rate (bpm^2 per hertz). Normal RFa is 0.5 to 8.0.
Time Frame
Baseline, week 4, week 8
Title
Effect of VNS on Mucosal Inflammation
Description
Median fluorescence intensity (MFI) data were preprocessed for each cytokine through a sequence of averaging over duplicate wells, natural-logarithm transformation to reduce variance heterogeneity, and isolation and removal of plate effects. The effects of VNS therapy on gastric and small intestine inflammation was measured as average fold change across all tissue cytokines from endoscopic mucosal biopsies before and after VNS, using cytokine multiplex assays, which report relative levels of various cytokines as adjusted mean fluorescence intensity (MFI).
Time Frame
Baseline (pre-VNS) and 4 weeks (post-VNS)
Title
The Effect of VNS Therapy on Gastric and Small Intestine Leukocyte Infiltration.
Description
The effects of VNS therapy on gastric and small intestine leukocyte infiltration was measured as relative abundance (normalized ratio) of immune cells (identified via CD45 marker) to total live cells across tissue leukocytes from endoscopic mucosal biopsies before and after VNS, using flow cytometry.
Time Frame
Baseline (pre-VNS) and 4 weeks (post-VNS)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female. Age 21-65 years old. Established diagnosis of functional dyspepsia, idiopathic or diabetic gastroparesis as per AGA (American Gastroenterology Association) guidelines. Patient is capable of giving informed consent and undergo upper endoscopy. Patient is on stable doses of other medications for gastroparesis for preceding 4 weeks prior to enrollment (baseline measures). Exclusion Criteria Surgical-related gastroparesis Extrinsic myopathy or neuropathy causing gastroparesis. Use of narcotic pain medications in the preceding 2 weeks of study enrollment. Patients with enteric feeding tubes or requiring parenteral nutrition (Patients with g-tubes who are stable for 3 months and not using the g-tube for venting may be eligible. patient with J-tubes are not eligible. Patients with severe flare requiring hospitalization. Untreated significant depression or suicidal thoughts. Pregnant or breast-feeding women. History of gastric pacemaker implantation. Patients with prior gastric surgery, including fundoplication, partial/total gastrectomy, or gastric bypass. Patients with malabsorption of enteric, pancreatic, or hepatibiliary etiology. Patients with primary pulmonary disorders that affect the spirulina breath test. Patients with implantable electronic devices. Patients with carotid artery atherosclerosis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andres Gottfried, MD PHD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Linda Nguyen, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University Medical Center
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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