xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06038929</url>
    </required_header>
    <id_info>
      <org_study_id>23-006558</org_study_id>
      <nct_id>NCT06038929</nct_id>
    </id_info>
    <brief_title>Effect of Vagal Nerve Stimulation on Gastric Motor Functions</brief_title>
    <official_title>REVEAL - Research Evaluating Vagal Excitation and Anatomical Linkages Gastric Emptying Ancillary Project: Effect of Vagal Nerve Stimulation on Gastric Motor Functions</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Mayo Clinic</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Minnesota</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Mayo Clinic</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The specific aim of this study is to compare simultaneous assessment of gastric emptying and&#xD;
        gastric accommodation in response to the same caloric meal before and three months after&#xD;
        activation of left cervical VNS. Our hypothesis is that cervical VNS increases gastric&#xD;
        accommodation and accelerates gastric emptying.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Objectives To compare simultaneous assessment of gastric emptying and gastric accommodation&#xD;
        in response to the same caloric meal before and three months after activation of left&#xD;
        cervical Vagal Nerve Stimulation.&#xD;
  &#xD;
        Design and Outcomes Single cohort study in 16 Vagus Nerve Stimulant-implanted subjects with&#xD;
        drug-resistant epilepsy with seizures, aged 18 years or older who were consented for the main&#xD;
        VESPA REVEAL Common Study Protocol.&#xD;
  &#xD;
        Prior to surgery, subjects will undergo combined gastric emptying/accommodation test.&#xD;
        Subsequently, participants will undergo a second identical study within 1 week of completing&#xD;
        the second Late Effects Visit in CSP, approximately 3 months after insertion of the VNS.&#xD;
        There are only 2 total visits needed, with an average time commitment of 4.5 hours.&#xD;
  &#xD;
        Participants will keep their planned VESPA REVEAL study visits Interventions and Duration In&#xD;
        this single cohort study in 16 Vagus Nerve Stimulant-implanted subjects, each participant&#xD;
        will undergo combined gastric emptying/accommodation test prior to implantation and a second&#xD;
        identical study within 1 week of completing the second Late Effects Visit in CSP Sample Size&#xD;
        and Population Sample size assessment. This will be based on results of the primary endpoints&#xD;
        in our Mayo Clinic lab. We expect 80% power, α=0.05, assuming paired t-test analysis with&#xD;
        n=16 first tested at baseline (no VNS) and 3 months after VNS activation with parameters as&#xD;
        described above. Demonstrable differences (Table 1) will be based on the variation (SD)&#xD;
        observed from our Mayo Clinic prior studies&#xD;
  &#xD;
        . Table 1. Effect size demonstrable for primary endpoints of interest, based on 80% power at&#xD;
        α=0.05 for n=16 Response Mean SD Effect size detectable [absolute (% of mean)] Fasting&#xD;
        gastric volume, mL 273 57 42.7mL (15.6%) Post-meal gastric volume, mL 848 111 83.2mL (9.8%)&#xD;
        Gastric emptying T1/2, min 122 29.8 22.33 (18.3%)&#xD;
  &#xD;
        In addition, these effect sizes are feasible in response to vagal intervention, whether it&#xD;
        turns out to be stimulatory or inhibitory, and a 20-minute difference in GE T1/2 is&#xD;
        clinically significant, as documented in a published meta-regression from our research team.&#xD;
  &#xD;
        Human subjects. Participants will be recruited primarily from the Mayo Clinic but also from&#xD;
        the University of Minnesota (90-minute drive away). With only limited added burden on&#xD;
        participants, we anticipate that the majority of n-VNS REVEAL participants from these two&#xD;
        sites (total = 16) will be amenable to undergo our procedures. There are only 2 total visits&#xD;
        needed, with an average time commitment of 4.5 hours.&#xD;
  &#xD;
        The patients will have undergone placement of the n-VNS for clinical indications. The&#xD;
        objective of the study is to evaluate the effects of this treatment on gastric functions,&#xD;
        rather than any therapeutic intent, or the development of a new indication to be submitted to&#xD;
        regulatory agencies for an additional therapeutic indication. Therefore, it is perceived that&#xD;
        an application for an investigational device exemption (IDE) is not required.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">June 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">March 31, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>Single cohort, open label study in 16 Vagus Nerve Stimulant-implanted subjects with drug-resistant epilepsy with seizures or depression, aged 18 years or older</intervention_model_description>
      <primary_purpose>Other</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Gastric emptying T1/2</measure>
      <time_frame>during 4 hour gastric emptying test</time_frame>
      <description>time to empty 50% of the whole stomach contents</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Gastric accommodation</measure>
      <time_frame>during first 1 hour of gastric emptying test</time_frame>
      <description>gastric delta volume (postprandial minus fasting) for the whole stomach</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Gastric emptying lag time</measure>
      <time_frame>1 day (during gastric emptying test)</time_frame>
      <description>time to empty 10% of the whole stomach</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gastric emptying 25%</measure>
      <time_frame>1 day (during gastric emptying test)</time_frame>
      <description>time to empty 25% of the whole stomach</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gastric emptying at 2 hours</measure>
      <time_frame>2 hours (during gastric emptying test)</time_frame>
      <description>% emptied from the whole stomach at 2h</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Gastric emptying at 4 hours</measure>
      <time_frame>4 hours (during gastric emptying test)</time_frame>
      <description>% emptied from the whole stomach at 4h</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fasting whole volume volume</measure>
      <time_frame>baseline</time_frame>
      <description>volume of whole stomach before ingestion of meal</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fasting proximal gastric volume</measure>
      <time_frame>baseline</time_frame>
      <description>volume of proximal half of stomach before ingestion of meal</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postprandial whole gastric volume</measure>
      <time_frame>10-30 minutes after meal ingestion</time_frame>
      <description>volume of whole stomach 10-30 minutes after ingestion of meal</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postprandial proximal gastric volume</measure>
      <time_frame>10-30 minutes after meal ingestion</time_frame>
      <description>volume of proximal half of stomach 10-30 minutes after ingestion of meal</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">16</enrollment>
    <condition>Epilepsy</condition>
    <condition>Depression</condition>
    <arm_group>
      <arm_group_label>vagal nerve stimulant</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The aim is to measure gastric emptying and gastric accommodation in response to a caloric meal before and 3 months after activation of VNS. Therefore, prior to surgery, subjects will undergo combined gastric emptying/accommodation test. Subsequently, participants will undergo a second identical study approximately 3 months after insertion of the VNS.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Vagal nerve stimulant</intervention_name>
      <description>Vagus nerve stimulation involves using a device to stimulate the vagus nerve with electrical impulses. The implanted electrodes transmit electrical impulses travel to areas of the brain to treat conditions (intractable epilepsy, depression) and also send electrical impulses to the stomach.</description>
      <arm_group_label>vagal nerve stimulant</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria&#xD;
  &#xD;
            1. Subject must be at least 18 years old.&#xD;
  &#xD;
            2. Subject must provide written informed consent and Health Insurance Portability and&#xD;
               Accountability Act (HIPAA) authorization&#xD;
  &#xD;
            3. Disabling seizures (Disabling seizures are those with significant negative impact on&#xD;
               the patient's life)&#xD;
  &#xD;
            4. Drug Resistant Epilepsy, with continuing seizures despite adequate trials of at least&#xD;
               2 appropriate anti-seizure drugs (ASDS) with therapeutic serum concentrations (as per&#xD;
               the International League Against Epilepsy (ILAE) Commission on Therapeutic Strategies)&#xD;
               (44).&#xD;
  &#xD;
            5. Not a good candidate for resective surgery as determined by our institution's&#xD;
               multidisciplinary epilepsy surgery committee&#xD;
  &#xD;
            6. Apart from epilepsy, subject should be medically and neurologically stable.&#xD;
  &#xD;
            7. Subject is able to complete regular office visits and telephone appointments including&#xD;
               the 2 imaging sessions in accordance with the study protocol requirements.&#xD;
  &#xD;
            8. Subject is a male or non-pregnant female adequately protected from conception, or&#xD;
               willing to use an acceptable method of birth control over the entire study duration if&#xD;
               of childbearing potential.&#xD;
  &#xD;
            9. Subject has been informed of his or her eligibility for resective surgery as a&#xD;
               potential alternative to the study if such surgery is a reasonable option.&#xD;
  &#xD;
          4.2 Exclusion Criteria&#xD;
  &#xD;
            1. Subject currently uses or during the study is expected to use short-wave diathermy,&#xD;
               microwave, diathermy, or therapeutic ultrasound diathermy.&#xD;
  &#xD;
            2. Subject has a substance abuse history (alcohol, prescription, or illicit medications)&#xD;
               within the preceding two years.&#xD;
  &#xD;
            3. Subject participated in another drug or device trial within the preceding 30 days&#xD;
               (other than the REVEAL main CSP).&#xD;
  &#xD;
            4. Subject has been hospitalized for a psychiatric condition within the preceding two&#xD;
               years or has had a history of psychosis within the preceding two years (excluding&#xD;
               post-ictal psychosis).&#xD;
  &#xD;
            5. Subject has experienced unprovoked status epilepticus in the preceding year.&#xD;
  &#xD;
            6. Subject is on anticoagulants and is unable to discontinue them peri-surgically, as&#xD;
               required by the neurosurgeon or Investigator.&#xD;
  &#xD;
            7. Subject has significant platelet dysfunction from medical conditions or medications&#xD;
               (including, particularly, aspirin or sodium valproate). If platelet dysfunction is&#xD;
               suspected, subject can be enrolled only if a hematologist, the Investigator, and the&#xD;
               neurosurgeon judge it to be advisable.&#xD;
  &#xD;
            8. Subject with vocal cord paralysis&#xD;
  &#xD;
            9. Any other factor that may impact participant safety or compliance as per PI.&#xD;
  &#xD;
           10. Subject cannot speak and read English.&#xD;
  &#xD;
           11. Prohibited Therapy During Study Period: We will exclude patients on&#xD;
               immunosuppressants, beta blockers, anticholinergics, and clonidine. Consultation with&#xD;
               primary providers and amending some of these therapies may be allowed only if&#xD;
               clinically indicated. In that case, participants will have to be stable on their new&#xD;
               medication for at least one month prior to implant.&#xD;
  &#xD;
           12. A body weight of over 350 pounds or 159 kilograms due to equipment limitations used in&#xD;
               the measurements of gastric accommodation and emptying.&#xD;
  &#xD;
           13. An inability to eat eggs whether due to an allergy, intolerance, or strong dislike.&#xD;
               The gastric emptying test meal contains eggs that are labeled with radioisotope. Other&#xD;
               food substitutions for the toast, butter and milk may be made only if prior approval&#xD;
               is given by Dr. Camilleri.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Michael Camilleri</last_name>
      <role>Principal Investigator</role>
      <affiliation>Mayo Clinic</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Mayo Clinic in Rochester</name>
        <address>
          <city>Rochester</city>
          <state>Minnesota</state>
          <zip>55905</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 10, 2023</study_first_submitted>
    <study_first_submitted_qc>September 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 14, 2023</last_update_submitted>
    <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Mayo Clinic</investigator_affiliation>
      <investigator_full_name>Michael Camilleri, MD</investigator_full_name>
      <investigator_title>Professor of Medicine, Pharmacology and Physiology</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Epilepsy</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Central Nervous System Stimulants</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06038929
  org study id: 23-006558
  nct id: NCT06038929
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: Yes
  The specific aim of this study is to compare simultaneous assessment of gastric emptying and
        gastric accommodation in response to the same caloric meal before and three months after
        activation of left cervical VNS. Our hypothesis is that cervical VNS increases gastric
        accommodation and accelerates gastric emptying.
  Objectives To compare simultaneous assessment of gastric emptying and gastric accommodation
        in response to the same caloric meal before and three months after activation of left
        cervical Vagal Nerve Stimulation.
  
        Design and Outcomes Single cohort study in 16 Vagus Nerve Stimulant-implanted subjects with
        drug-resistant epilepsy with seizures, aged 18 years or older who were consented for the main
        VESPA REVEAL Common Study Protocol.
  
        Prior to surgery, subjects will undergo combined gastric emptying/accommodation test.
        Subsequently, participants will undergo a second identical study within 1 week of completing
        the second Late Effects Visit in CSP, approximately 3 months after insertion of the VNS.
        There are only 2 total visits needed, with an average time commitment of 4.5 hours.
  
        Participants will keep their planned VESPA REVEAL study visits Interventions and Duration In
        this single cohort study in 16 Vagus Nerve Stimulant-implanted subjects, each participant
        will undergo combined gastric emptying/accommodation test prior to implantation and a second
        identical study within 1 week of completing the second Late Effects Visit in CSP Sample Size
        and Population Sample size assessment. This will be based on results of the primary endpoints
        in our Mayo Clinic lab. We expect 80% power, α=0.05, assuming paired t-test analysis with
        n=16 first tested at baseline (no VNS) and 3 months after VNS activation with parameters as
        described above. Demonstrable differences (Table 1) will be based on the variation (SD)
        observed from our Mayo Clinic prior studies
  
        . Table 1. Effect size demonstrable for primary endpoints of interest, based on 80% power at
        α=0.05 for n=16 Response Mean SD Effect size detectable [absolute (% of mean)] Fasting
        gastric volume, mL 273 57 42.7mL (15.6%) Post-meal gastric volume, mL 848 111 83.2mL (9.8%)
        Gastric emptying T1/2, min 122 29.8 22.33 (18.3%)
  
        In addition, these effect sizes are feasible in response to vagal intervention, whether it
        turns out to be stimulatory or inhibitory, and a 20-minute difference in GE T1/2 is
        clinically significant, as documented in a published meta-regression from our research team.
  
        Human subjects. Participants will be recruited primarily from the Mayo Clinic but also from
        the University of Minnesota (90-minute drive away). With only limited added burden on
        participants, we anticipate that the majority of n-VNS REVEAL participants from these two
        sites (total = 16) will be amenable to undergo our procedures. There are only 2 total visits
        needed, with an average time commitment of 4.5 hours.
  
        The patients will have undergone placement of the n-VNS for clinical indications. The
        objective of the study is to evaluate the effects of this treatment on gastric functions,
        rather than any therapeutic intent, or the development of a new indication to be submitted to
        regulatory agencies for an additional therapeutic indication. Therefore, it is perceived that
        an application for an investigational device exemption (IDE) is not required.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Single cohort, open label study in 16 Vagus Nerve Stimulant-implanted subjects with drug-resistant epilepsy with seizures or depression, aged 18 years or older
  primary purpose: Other
  masking: None (Open Label)
  measure: Gastric emptying T1/2
  time frame: during 4 hour gastric emptying test
  description: time to empty 50% of the whole stomach contents
  measure: Gastric accommodation
  time frame: during first 1 hour of gastric emptying test
  description: gastric delta volume (postprandial minus fasting) for the whole stomach
  measure: Gastric emptying lag time
  time frame: 1 day (during gastric emptying test)
  description: time to empty 10% of the whole stomach
  measure: Gastric emptying 25%
  time frame: 1 day (during gastric emptying test)
  description: time to empty 25% of the whole stomach
  measure: Gastric emptying at 2 hours
  time frame: 2 hours (during gastric emptying test)
  description: % emptied from the whole stomach at 2h
  measure: Gastric emptying at 4 hours
  time frame: 4 hours (during gastric emptying test)
  description: % emptied from the whole stomach at 4h
  measure: Fasting whole volume volume
  time frame: baseline
  description: volume of whole stomach before ingestion of meal
  measure: Fasting proximal gastric volume
  time frame: baseline
  description: volume of proximal half of stomach before ingestion of meal
  measure: Postprandial whole gastric volume
  time frame: 10-30 minutes after meal ingestion
  description: volume of whole stomach 10-30 minutes after ingestion of meal
  measure: Postprandial proximal gastric volume
  time frame: 10-30 minutes after meal ingestion
  description: volume of proximal half of stomach 10-30 minutes after ingestion of meal
  arm group label: vagal nerve stimulant
  arm group type: Experimental
  description: The aim is to measure gastric emptying and gastric accommodation in response to a caloric meal before and 3 months after activation of VNS. Therefore, prior to surgery, subjects will undergo combined gastric emptying/accommodation test. Subsequently, participants will undergo a second identical study approximately 3 months after insertion of the VNS.
  intervention type: Device
  intervention name: Vagal nerve stimulant
  description: Vagus nerve stimulation involves using a device to stimulate the vagus nerve with electrical impulses. The implanted electrodes transmit electrical impulses travel to areas of the brain to treat conditions (intractable epilepsy, depression) and also send electrical impulses to the stomach.
  arm group label: vagal nerve stimulant
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Michael Camilleri
  role: Principal Investigator
  affiliation: Mayo Clinic
  facility: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Mayo Clinic
  investigator full name: Michael Camilleri, MD
  investigator title: Professor of Medicine, Pharmacology and Physiology
  mesh term: Epilepsy
  mesh term: Central Nervous System Stimulants