<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/NCT02232919</url>
  </required_header>
  <id_info>
    <org_study_id>230/2012</org_study_id>
    <nct_id>NCT02232919</nct_id>
  </id_info>
  <brief_title>Deep Brain Stimulation for Human Morbid Obesity</brief_title>
  <acronym>BLESS</acronym>
  <official_title>Hypothalamus Deep Brain Stimulation for Human Morbid Obesity: Feasibility Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital do Coracao</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital do Coracao</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The burden of morbid obesity to the circulatory, endocrine, and locomotor systems, as well as&#xD;
      the psychological effects and related health-care costs, are well established in the medical&#xD;
      literature. Lifestyle and dietary patterns remain critical factors modulating long-term&#xD;
      weight control of morbidly obese individuals (bodymass index ≥ 40). Various dietary,&#xD;
      pharmacological, and behavioral interventions have largely failed as therapies, often&#xD;
      necessitating surgery as the last treatment option. Long term results of bariatric surgery&#xD;
      suggest that sustained and substantial weight loss can decrease morbidity related to obesity&#xD;
      secondary complications such as diabetes type 2 and cancers, enhancing the role of surgery&#xD;
      for morbidly obese subjects. However the adverse effects of bariatric surgery are&#xD;
      considerable and impact on quality of life. Its long-term failure rates and complications&#xD;
      call for novel and effective long-term therapies, such as neurosurgical interventions.&#xD;
&#xD;
      The investigators now propose to enhance our targeting capabilities in a feasibility study of&#xD;
      low frequency electrical stimulation using VMH-DBS (ventromedial hypothalamic) in six&#xD;
      morbidly obese patients. After successful targeting, DBS stimulation parameters will be&#xD;
      systematically evaluated and individually optimized at three-month intervals over a one-year&#xD;
      stimulation period. Detailed recording of side effects, weight changes, food intake patterns,&#xD;
      metabolic changes, and behavioral evaluations will be obtained throughout the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Neuromodulation of metabolism and feeding behavior is at hand using modern systems of deep&#xD;
      brain stimulation (DBS). It constitutes a minimally invasive approach for these challenging&#xD;
      patients. The surgical procedure is reversible and proven to have acceptable side effects in&#xD;
      the frail population of Parkinson's disease patients [Gorgulho, Hemorrhage and Infection].&#xD;
      Improvement of functional stereotactic surgery methods is necessary however to the challenge&#xD;
      of implanting DBS electrodes in the hypothalamus. Recently, a case report of a patient with&#xD;
      DBS implanted in the hypothalamus for treatment of morbid obesity who reported side effects&#xD;
      related to memory appeared in the literature. The authors used the side effect findings to&#xD;
      suggest the location of their implant as a site for treatment of Alzheimer's disease. This&#xD;
      illustrates the need of betterment of our techniques of targeting in DBS surgery, especially&#xD;
      for targets located in highly functional structures, such as the hypothalamus.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">April 2016</primary_completion_date>
  <phase>Phase 1</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Identification of possible adverse events related to stimulation of the VMH</measure>
    <time_frame>12 months</time_frame>
    <description>To identify potential side effects of continuous electrical stimulation of the VMH and optimize electrophysiological parameters to avoid these side effects in morbidly obese subjects.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Body Weight</measure>
    <time_frame>12 months</time_frame>
    <description>To determine if continuous VMH-DBS will lead to weight loss in morbidly obese subjects. Baseline measurements of body weight [kg, lb] will be recorded on 3 different occasions prior to DBS implantation. The baseline weight will be considered the arithmetic mean of these measurements. Body weight will be recorded at every follow-up visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Composition</measure>
    <time_frame>12 months</time_frame>
    <description>To determine if continuous electrical stimulation of the VMH will lead to changes in body composition. Measurements of body composition will be evaluated by Dual-Energy Xray Absorptiometry [DEXA] at baseline and at 3 month intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Food Intake.</measure>
    <time_frame>12 months</time_frame>
    <description>To determine if VMH-DBS will cause decreased food intake. Subjects will complete a questionnaire during the monthly visit assisted by the study coordinator. Data reflecting food quality and quantity will be compiled for analysis and correlation with the other parameters obtained in the study.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Deep Brain Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The design of this translation trial is a single-center, single cohort, open-label and non-masked study. The aim is to evaluate tolerability of chronic low-frequency electrical stimulation of the VMH, while achieving weight loss in morbidly obese subjects. The subjects must have a body-mass index [BMI] greater than 40, and no obesity co-morbidities, such as diabetes or cardiopulmonary abnormalities. Up to six subjects will be implanted in this protocol.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Deep Brain Stimulation</intervention_name>
    <description>If subjects qualify with respect to protocol requirements, the Medtronic Activa system will be implanted with the leads placed bilaterally in the VMH.&#xD;
Adjustment of DBS parameters at the three months visit will be performed to improve efficacy when the goal of 3% body weight loss mark was not achieved during this period of continuous stimulation. Subjects will be seen monthly after discharge throughout the study period. At visits, safety will be assessed through blood/urine tests, blood pressure measurements, verbal interviews with the subjects and family, quarterly formal psychiatric tests as well as QOL scales.&#xD;
The determination of efficacy will be the within-group percent change in weight at the end of the DBS treatment period compared to baseline.</description>
    <arm_group_label>Deep Brain Stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Body Mass Index [BMI] &gt;40 kg/m2. BMI definition = weight [Kg] / height [m]2&#xD;
&#xD;
          2. Failed diet, exercise, behavior, and pharmacotherapy to control body weight.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Cancer requiring treatment in the past five years, with the exception of cancers which&#xD;
             have been cured or, in the opinion of the investigator, carry a good prognosis [for&#xD;
             example, non melanoma skin cancer].&#xD;
&#xD;
          2. Infectious disease [e.g., HIV or active tuberculosis].&#xD;
&#xD;
          3. Cardiovascular disease:&#xD;
&#xD;
             i. Hospitalization for treatment of heart disease in the past 6 months. ii. New York&#xD;
             Heart Association Functional Class &gt;2. iii. Left bundle branch block on EKG. iv. Third&#xD;
             degree atrioventricular block on EKG. v. Uncontrolled hypertension [average systolic&#xD;
             blood pressure of &gt;160 mmHg or diastolic blood pressure &gt;95 mmHg on both screening&#xD;
             visits].&#xD;
&#xD;
             vi. Pulse rate &gt;95 beats per minute on both screening visits. vii. Total serum&#xD;
             cholesterol &gt;300 mg/dL. viii. Stroke or transient ischemic attack in the past 6&#xD;
             months.&#xD;
&#xD;
          4. Gastrointestinal disease:&#xD;
&#xD;
             i. Chronic hepatitis or cirrhosis. ii. Episode of alcoholic hepatitis or alcoholic&#xD;
             pancreatitis. iii. Inflammatory bowel disease requiring treatment in the past year.&#xD;
             iv. Recent or significant abdominal surgery [e.g., gastrectomy or gastric bypass].&#xD;
&#xD;
          5. Renal disease:&#xD;
&#xD;
             i. Serum creatinine &gt;1.5 mg/dL. ii. Urine protein&gt;2+ on dipstick at screening and or&#xD;
             24-hour urinary excretion of albumin&gt;500 mg/day.&#xD;
&#xD;
          6. Lung disease:&#xD;
&#xD;
             i. Chronic obstructive airway disease or asthma requiring daily therapy. ii. Use of&#xD;
             home oxygen.&#xD;
&#xD;
          7. Endocrine disease:&#xD;
&#xD;
             i. Diabetes mellitus. ii. Hyperlipidemia with triacylglycerol &gt;500 mg/dL. iii.&#xD;
             Hypothyroidism, hyperthyroidism. iv. Hypopituitarism. v. Hypogonadism.&#xD;
&#xD;
          8. Psychological Disease:&#xD;
&#xD;
             i. Major clinical depression. ii. Active psychiatric disorders. iii. Schizophrenia.&#xD;
&#xD;
          9. Hematology i. Anemia [hematocrit &lt;36.0%]. ii. Bleeding disorders, thrombocytopenia,&#xD;
             thrombocytosis.&#xD;
&#xD;
         10. Conditions or behaviors likely to affect the conduct of the study:&#xD;
&#xD;
             i. Unable or unwilling to give informed consent. ii. Unable to communicate with the&#xD;
             clinic staff. iii. Weight loss &gt;10% in the past 6 months. iv. Unable to walk 0.25&#xD;
             miles in 10 minutes. v. Behavioral disorder which, in the opinion of the investigator,&#xD;
             would impede conduct of the study.&#xD;
&#xD;
             vi. Excessive alcohol intake, use of illicit drugs.&#xD;
&#xD;
         11. Conditions related to medications:&#xD;
&#xD;
             i. Psychoactive agents. ii. Monoamine oxidase inhibitors [e.g., phenelzine,&#xD;
             procarbazine, selegiline, furazolidone].&#xD;
&#xD;
             iii. Antidepressants [e.g., lithium, fluoxetine, sertraline, nefazodone, paroxetine,&#xD;
             venlafaxine].&#xD;
&#xD;
             iv. Any other medication that, in the opinion of the investigator, may pose harm to&#xD;
             the subject.&#xD;
&#xD;
         12. Seizure disorders.&#xD;
&#xD;
         13. Receiving anticoagulation medications or likely to need anticoagulation in the&#xD;
             foreseeable future.&#xD;
&#xD;
         14. Subject is not a surgical candidate.&#xD;
&#xD;
         15. Lack of social support.&#xD;
&#xD;
         16. Inability to comply with testing and follow-up visit requirements defined by the Study&#xD;
             Protocol.&#xD;
&#xD;
         17. Subject has another implanted device or metallic object [e.g., cardiac demand&#xD;
             pacemakers, aneurysm clips, cochlear implant, spinal cord stimulator, etc].&#xD;
&#xD;
         18. Subject has a medical condition that might require repeat MRIs.&#xD;
&#xD;
         19. Subject has concurrent infection.&#xD;
&#xD;
         20. Subject has any medical condition contraindicating a chronically implanted device.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alessandra Gorgulho, MD, MSc</last_name>
    <role>Study Chair</role>
    <affiliation>HOSPITAL DO CORAÇÃO</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antonio De Salles, M.D., Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>HOSPITAL DO CORAÇÃO</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Otavio Berwanger, MD,PhD</last_name>
    <role>Study Director</role>
    <affiliation>HOSPITAL DO CORAÇÃO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital do Coracao</name>
      <address>
        <city>São Paulo</city>
        <state>Sao Paulo</state>
        <zip>04005-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <last_update_submitted>September 28, 2016</last_update_submitted>
  <last_update_submitted_qc>September 28, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 29, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Deep Brain Stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
    <mesh_term>Obesity, Morbid</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT02232919
org study id: 230/2012
nct id: NCT02232919
lead sponsor: 
has dmc: Yes
The burden of morbid obesity to the circulatory, endocrine, and locomotor systems, as well as
      the psychological effects and related health-care costs, are well established in the medical
      literature. Lifestyle and dietary patterns remain critical factors modulating long-term
      weight control of morbidly obese individuals (bodymass index ≥ 40). Various dietary,
      pharmacological, and behavioral interventions have largely failed as therapies, often
      necessitating surgery as the last treatment option. Long term results of bariatric surgery
      suggest that sustained and substantial weight loss can decrease morbidity related to obesity
      secondary complications such as diabetes type 2 and cancers, enhancing the role of surgery
      for morbidly obese subjects. However the adverse effects of bariatric surgery are
      considerable and impact on quality of life. Its long-term failure rates and complications
      call for novel and effective long-term therapies, such as neurosurgical interventions.

      The investigators now propose to enhance our targeting capabilities in a feasibility study of
      low frequency electrical stimulation using VMH-DBS (ventromedial hypothalamic) in six
      morbidly obese patients. After successful targeting, DBS stimulation parameters will be
      systematically evaluated and individually optimized at three-month intervals over a one-year
      stimulation period. Detailed recording of side effects, weight changes, food intake patterns,
      metabolic changes, and behavioral evaluations will be obtained throughout the study.
Neuromodulation of metabolism and feeding behavior is at hand using modern systems of deep
      brain stimulation (DBS). It constitutes a minimally invasive approach for these challenging
      patients. The surgical procedure is reversible and proven to have acceptable side effects in
      the frail population of Parkinson's disease patients [Gorgulho, Hemorrhage and Infection].
      Improvement of functional stereotactic surgery methods is necessary however to the challenge
      of implanting DBS electrodes in the hypothalamus. Recently, a case report of a patient with
      DBS implanted in the hypothalamus for treatment of morbid obesity who reported side effects
      related to memory appeared in the literature. The authors used the side effect findings to
      suggest the location of their implant as a site for treatment of Alzheimer's disease. This
      illustrates the need of betterment of our techniques of targeting in DBS surgery, especially
      for targets located in highly functional structures, such as the hypothalamus.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Identification of possible adverse events related to stimulation of the VMH
time frame: 12 months
description: To identify potential side effects of continuous electrical stimulation of the VMH and optimize electrophysiological parameters to avoid these side effects in morbidly obese subjects.
measure: Body Weight
time frame: 12 months
description: To determine if continuous VMH-DBS will lead to weight loss in morbidly obese subjects. Baseline measurements of body weight [kg, lb] will be recorded on 3 different occasions prior to DBS implantation. The baseline weight will be considered the arithmetic mean of these measurements. Body weight will be recorded at every follow-up visit.
measure: Body Composition
time frame: 12 months
description: To determine if continuous electrical stimulation of the VMH will lead to changes in body composition. Measurements of body composition will be evaluated by Dual-Energy Xray Absorptiometry [DEXA] at baseline and at 3 month intervals.
measure: Food Intake.
time frame: 12 months
description: To determine if VMH-DBS will cause decreased food intake. Subjects will complete a questionnaire during the monthly visit assisted by the study coordinator. Data reflecting food quality and quantity will be compiled for analysis and correlation with the other parameters obtained in the study.
arm group label: Deep Brain Stimulation
arm group type: Experimental
description: The design of this translation trial is a single-center, single cohort, open-label and non-masked study. The aim is to evaluate tolerability of chronic low-frequency electrical stimulation of the VMH, while achieving weight loss in morbidly obese subjects. The subjects must have a body-mass index [BMI] greater than 40, and no obesity co-morbidities, such as diabetes or cardiopulmonary abnormalities. Up to six subjects will be implanted in this protocol.
intervention type: Device
intervention name: Deep Brain Stimulation
description: If subjects qualify with respect to protocol requirements, the Medtronic Activa system will be implanted with the leads placed bilaterally in the VMH.
Adjustment of DBS parameters at the three months visit will be performed to improve efficacy when the goal of 3% body weight loss mark was not achieved during this period of continuous stimulation. Subjects will be seen monthly after discharge throughout the study period. At visits, safety will be assessed through blood/urine tests, blood pressure measurements, verbal interviews with the subjects and family, quarterly formal psychiatric tests as well as QOL scales.
The determination of efficacy will be the within-group percent change in weight at the end of the DBS treatment period compared to baseline.
arm group label: Deep Brain Stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Alessandra Gorgulho, MD, MSc
role: Study Chair
affiliation: HOSPITAL DO CORAÇÃO
last name: Antonio De Salles, M.D., Ph.D.
role: Study Chair
affiliation: HOSPITAL DO CORAÇÃO
last name: Otavio Berwanger, MD,PhD
role: Study Director
affiliation: HOSPITAL DO CORAÇÃO
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Obesity
mesh term: Obesity, Morbid