Effect of Vagal Nerve Stimulation on Gastric Motor Functions

General criteria

1. Participant must be at least 18 years old.

2. Participant must have the capacity to provide written informed consent and HealthInsurance Portability and Accountability Act (HIPAA) authorization.

3. Participant is diagnosed with drug Resistant Epilepsy and previously underwentimplantation of VNS. and/or

4. Participant is diagnosed with treatment-refractory depression and previouslyunderwent implantation of VNS.

5. Participant has completed the REVEAL CSP and has been stabilized by their care teamon a stable VNS setting

6. Apart from epilepsy or depression, participant should be medically andneurologically stable.

7. Participant is able to complete regular office visits and telephone appointmentsincluding the imaging session in accordance with the study protocol requirements.

8. Participant that is of childbearing potential must be adequately protected fromconception or willing to use an acceptable method of birth control over the entirestudy duration (acceptable birth control includes abstinence, barrier methods,hormonal methods, sterilization and fertility awareness).

9. Participant must be enrolled in an active health insurance plan that will cover thecosts associated with standard health care services and injuries.

Exclusion Criteria: GENERAL criteria

1. Participant has a prior implantable stimulation device other than a VNS device forthe clinical indication of refractory focal Epilepsy or for depression.

2. Participant currently uses or during the study is expected to use short-wavediathermy, microwave, diathermy, or therapeutic ultrasound diathermy.

3. Participant has a diagnosis of Substance Use Disorder as defined by DSM-5 withoutsustained remission of 12 months or longer.

4. Patient participated in another drug or device trial within the preceding 30 days (other than REVEAL studies).

5. Participant has been hospitalized for a psychiatric condition within the preceding 6months or has had a history of psychosis within the preceding two years (excludingpost-ictal psychosis).

6. Participant has experienced unprovoked status epilepticus in the preceding year.

7. Participant is not able or willing to use their dominant arm, or either upper armcircumference is greater than 50 cm.

8. Any other clinical reasons deemed by the investigators of the study for which theparticipant would not be an appropriate candidate for the study, such as peripheralvascular disease, Raynaud's phenomenon, orthostatic hypotension (OH), posturalorthostatic tachycardia syndrome (POTS), uncontrolled obstructive sleep apnea (OSA),chronic obstructive pulmonary disease (COPD), or uncontrolled diabetes or pregnancy

9. Participant with vocal cord paralysis

10. Participant cannot speak and read English.

11. Participant is pregnant.

12. Prohibited Therapy During Study Period: We will exclude patients onimmunosuppressants, beta blockers, anticholinergics, and clonidine. Consultationwith primary providers and amending some of these therapies may be allowed only ifclinically indicated. In that case, participants will have to be stable on their newmedication for at least one month prior to implant.

13. A body weight of over 350 pounds or 159 kilograms due to equipment limitations usedin the measurements of gastric accommodation and emptying.

14. An inability to eat eggs whether due to an allergy, intolerance, or strong dislike.The gastric emptying test meal contains eggs that are labeled with radioisotope.Other food substitutions for the toast, butter and milk may be made only if priorapproval is given by Dr. Camilleri.

15. Any other factor that may impact participant safety or compliance as per PI.

Since participants with pVNS will be recruited from the CSP study at U Minnesota, it is important to specify the inclusion and exclusion criteria for participants with drug-resistant epilepsy or drug-resistant depression who entered the CSP study:

Inclusion Criteria for Participants With Major Depressive Disorder That Have a Previously Implanted VNS Device

1. Participant must be at least 18 years old.

2. Participant must have the capacity to provide written informed consent and HealthInsurance Portability and Accountability Act (HIPAA) authorization.

3. Participant must be enrolled in an active health insurance plan that will cover thecosts associated with standard health care services and injuries.

4. Participant must have been previously implanted with a VNS device for the clinicalindication of Major Depressive Disorder (MDD).

5. Participant must have a score on the baseline administration of theMontgomery-Åsberg Depression Rating Scale (MADRS) of ≥ 22.

6. Participant must be able and willing to complete the evaluations and proceduresdescribed in the study protocol.

7. Participant must be able and willing to follow the stipulations regardingconcomitant medications and excluded medications described in section 5.3 of thestudy protocol.

8. Participant that is of childbearing potential must be adequately protected fromconception or willing to use an acceptable method of birth control over the entirestudy duration (acceptable birth control includes abstinence, barrier methods,hormonal methods, sterilization and fertility awareness).

Exclusion Criteria for Participants With Major Depressive Disorder That Have a Previously Implanted VNS Device

1. Participant has a prior implantable stimulation device, other than a VNS device forthe clinical indication of Major Depressive Disorder (MDD).

2. Participant currently uses or is expected during the study to use short-wavediathermy, microwave, diathermy, or therapeutic ultrasound diathermy.

3. Participant is judged by the investigator to be acutely suicidal (e.g. has madespecific plans or preparations to commit suicide or as indicated by the SheehanSuicidality Tracking Scale) within the last 30 days prior to study enrollment.

4. Participant has made a suicide attempt within the previous 6 months from studyenrollment.

5. Participant has a history of one or more schizophrenia-spectrum or other psychoticdisorders including schizophrenia, schizoaffective disorder, delusional disorder, ora current or lifetime major depressive episode that includes psychotic features (commonly referred to as psychotic depression) according to the MINI criteria.

6. Participant has a history of significant borderline or severe personality disorderas determined by clinical judgment.

7. Participant has an active primary diagnosis of obsessive-compulsive, eating, orpost-traumatic stress disorder based on the MINI criteria.

8. Participant has a diagnosis of Substance Use Disorder as defined by DSM-5 withoutsustained remission of 12 months or longer.

9. Participant has a presence of any type of dementia, major neurocognitive disorder,or cognitive or psychiatric deficit as determined by clinical judgment.

10. Participant has a history of rapid cycling bipolar disorder I or II.

11. Participant currently receives treatment with another investigational device orinvestigational drug other than the REVEAL study (or a REVEAL ancillary project orsub-study) or has participated in another drug or device trial within the preceding 30 days before enrollment.

12. Participant is not able or willing to use their dominant arm, or either upper armcircumference is greater than 50 cm.

13. Participant does not speak English.

14. Participant is pregnant.

15. Any other clinical reasons deemed by the investigators of the study for which theparticipant would not be an appropriate candidate for the study, such as peripheralvascular disease, Raynaud's phenomenon, orthostatic hypotension (OH), posturalorthostatic tachycardia syndrome (POTS), uncontrolled obstructive sleep apnea (OSA),chronic obstructive pulmonary disease (COPD), or uncontrolled diabetes.

Inclusion Criteria for Participants With Drug Resistant Epilepsy That Have a Previously Implanted VNS Device

1. Participant must be at least 18 years old.

2. Participant must have the capacity to provide written informed consent and HealthInsurance Portability and Accountability Act (HIPAA) authorization.

3. Participant must be enrolled in an active health insurance plan that will cover thecosts associated with standard health care services and injuries.

4. Participant must have been previously implanted with a VNS device for the clinicalindication of drug resistant epilepsy.

5. Participant has not had demonstrable benefit from the implanted VNS device in termsof epilepsy (seizure frequency or seizure severity) or related epilepsycomorbidities (mood, cognition, quality of life), with no definite improvement orsuboptimal improvement in seizure control.

6. Apart from epilepsy, the participant should be medically and neurologically stable.

7. Participant must be able and willing to complete the evaluations and proceduresdescribed in the study protocol.

8. Participant must be able and willing to follow the stipulations regardingconcomitant medications and excluded medications described in section 5.3 of thestudy protocol.

9. Participant that is of childbearing potential must be adequately protected fromconception or willing to use an acceptable method of birth control over the entirestudy duration (acceptable birth control includes abstinence, barrier methods,hormonal methods, sterilization and fertility awareness).

Exclusion Criteria for Participants With Drug Resistant Epilepsy That Have a Previously Implanted VNS Device

1. Participant has demonstrable benefit from implanted VNS device in terms of epilepsy (seizure frequency or seizure severity) or epilepsy comorbidity (mood, cognition, orquality of life), with seizure freedom or clinical benefit.

2. Participant has a prior implantable stimulation device, other than a VNS device forthe clinical indication of refractory focal Epilepsy.

3. Participant currently uses or is expected during the study to use short-wavediathermy, microwave, diathermy, or therapeutic ultrasound diathermy.

4. Participant has been hospitalized for a psychiatric condition within the preceding 6months or has had a history of psychosis within the preceding two years (excludingpostictal psychosis).

5. Participant has experienced unprovoked status epilepticus in the preceding year.

6. Participant has a diagnosis of Substance Use Disorder as defined by DSM-5 withoutsustained remission of 12 months or longer.

7. Participant currently receives treatment with another investigational device orinvestigational drug other than the REVEAL study (or a REVEAL ancillary project orsub-study) or has participated in another drug or device trial within the preceding 30 days before enrollment.

8. Participant is not able or willing to use their dominant arm, or either upper armcircumference is greater than 50 cm.

9. Participant does not speak English.

10. Participant is pregnant.

11. Any other clinical reasons deemed by the investigators of the study for which theparticipant would not be an appropriate candidate for the study, such as peripheralvascular disease, Raynaud's phenomenon, orthostatic hypotension (OH), posturalorthostatic tachycardia syndrome (POTS), uncontrolled obstructive sleep apnea (OSA),chronic obstructive pulmonary disease (COPD), or uncontrolled diabetes.