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Recruitment challenges due to the COVID19 pandemic and funding not available to restart.
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Idiopathic Gastroparesis | Experimental | 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. |
|
| Diabetic Gastroparesis | Experimental | 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. |
|
| Functional Dyspepsia | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vagal Nerve Stimulation | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Baseline (2 weeks prior to initiation), week 4 (7 days), week 8 (7 days) |
| 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. | Baseline and week 4 (3 hours to assess at each time point) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Andres Gottfried, MD PHD | Stanford University | Principal Investigator |
| Linda Nguyen, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University Medical Center | Redwood City | California | 94063 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Idiopathic Gastroparesis | Patients with idiopathic gastroparesis and delayed gastric emptying self-administer 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). |
| FG001 | Diabetic Gastroparesis | Patients with diabetic gastroparesis and delayed gastric emptying self-administer 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). |
| FG002 | Functional Dyspepsia | Patients with functional dyspepsia and normal gastric emptying self-administer 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). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Participants who received treatment
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| ID | Title | Description |
|---|---|---|
| BG000 | Idiopathic Gastroparesis | Patients with idiopathic gastroparesis and delayed gastric emptying self-administer 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). |
| BG001 | Diabetic Gastroparesis |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Participants who received treatment are included in the analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline (2 weeks prior to initiation), week 4 (7 days), week 8 (7 days) |
|
Baseline through week 8
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Idiopathic Gastroparesis | Patients with idiopathic gastroparesis and delayed gastric emptying self-administer 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). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
This trial had recruitment challenges due to the COVID19 pandemic with added cost of COVID testing prior to procedures. The idiopathic gastroparesis arm completed its planned enrollment but the other cohorts did not.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Linda Nguyen | Stanford University | 650-736-0431 | nguyenlb@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 14, 2017 | Jan 25, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D018589 | Gastroparesis |
| ID | Term |
|---|---|
| D013272 | Stomach Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D010243 | Paralysis |
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| ID | Term |
|---|---|
| D055536 | Vagus Nerve Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
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15 participants planned enrollment in each arm:
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|
| Baseline, week 4, week 8 |
| 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. | Baseline, week 4, week 8 |
| 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 | 8 weeks |
| 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. | Baseline, week 4, week 8 |
| 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). | Baseline (pre-VNS) and 4 weeks (post-VNS) |
| 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. | Baseline (pre-VNS) and 4 weeks (post-VNS) |
Patients with diabetic gastroparesis and delayed gastric emptying self-administer 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). |
| BG002 | Functional Dyspepsia | Patients with functional dyspepsia and normal gastric emptying self-administer 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). |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Plasma cytokines | Luminex assay 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 the removal of plate effects. The average (mean) value across all cytokines is reported. | Data were not collected for the "Diabetic Gastroparesis" and "Functional Dyspepsia" groups. | Mean | Standard Deviation | Normalized mean fluoresc ent intensity |
|
| OG001 | Diabetic Gastroparesis | Patients with diabetic gastroparesis and delayed gastric emptying self-administer 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). |
| OG002 | Functional Dyspepsia | Patients with functional dyspepsia and normal gastric emptying self-administer 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). |
|
|
| Primary | 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. | Participants who received treatment are included in the analysis. | Posted | Mean | Standard Deviation | minutes | Baseline and week 4 (3 hours to assess at each time point) |
|
|
|
| Secondary | 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. | Participants who received treatment and with data at the respective time point are included in the analysis. | Posted | Mean | Standard Deviation | T-score | Baseline, week 4, week 8 |
|
|
|
| Secondary | 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. | Participants who received treatment and with data at the respective time point are included in the analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline, week 4, week 8 |
|
|
|
| Secondary | 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 | Posted | Count of Participants | Participants | 8 weeks |
|
|
|
| Secondary | 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. | Participants who received treatment and with data at the respective time point are included in the analysis. | Posted | Mean | Standard Deviation | RFA (bpm^2/hertz) | Baseline, week 4, week 8 |
|
|
|
| Secondary | 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). | Participants who received treatment in the Idiopathic Gastroparesis group; data were not collected in the Diabetic Gastroparesis or Functional Dyspepsia groups. | Posted | Mean | Standard Deviation | fold change of MFI | Baseline (pre-VNS) and 4 weeks (post-VNS) | Cytokines | Cytokines |
|
|
|
| Secondary | 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. | Participants who received treatment in the Idiopathic Gastroparesis group; data were not collected in the Diabetic Gastroparesis or Functional Dyspepsia groups. | Posted | Mean | Standard Deviation | immune cell:total live cell ratio | Baseline (pre-VNS) and 4 weeks (post-VNS) |
|
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|
| 0 |
| 17 |
| 0 |
| 17 |
| 1 |
| 17 |
| EG001 | Diabetic Gastroparesis | Patients with diabetic gastroparesis and delayed gastric emptying self-administer 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). | 0 | 1 | 0 | 1 | 0 | 1 |
| EG002 | Functional Dyspepsia | Patients with functional dyspepsia and normal gastric emptying self-administer 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). | 0 | 6 | 0 | 6 | 0 | 6 |
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| D009461 |
| Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Between 18 and 65 years |
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| >=65 years |
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| Male |
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