<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/NCT04430582</url>
  </required_header>
  <id_info>
    <org_study_id>00000098</org_study_id>
    <nct_id>NCT04430582</nct_id>
  </id_info>
  <brief_title>Cognition in Patients With Hypoglycemia, Without Diabetes</brief_title>
  <official_title>Pilot Study - Cognition in Patients With Hypoglycemia, Without Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Joslin Diabetes Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Joslin Diabetes Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if there is a relationship between recurrent&#xD;
      hypoglycemia (low blood sugar) and cognition (thinking) in individuals who have a history of&#xD;
      hypoglycemia, but do not have pre-diabetes or diabetes.&#xD;
&#xD;
      This study will analyze whether recurrent hypoglycemia is associated with differences in&#xD;
      cognition (thinking), and if individuals with a history of hypoglycemia perform less well on&#xD;
      cognitive assessments compared to individuals without known hypoglycemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will test the hypothesis that recurrent hypoglycemia is associated with&#xD;
      differences in cognition (thinking), by analyzing results of cognitive testing in individuals&#xD;
      with a history of hypoglycemia as compared with those without known hypoglycemia.&#xD;
&#xD;
      This pilot study will identify cognitive domains of interest in participants with&#xD;
      hypoglycemia, as well as inform the development of a future battery of assessments, which&#xD;
      could be replicated in a larger sample. Cognitive domains which will be assessed include:&#xD;
      memory, language, executive function, and psychomotor speed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 4, 2020</start_date>
  <completion_date type="Anticipated">April 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of verbal memory</measure>
    <time_frame>March 2025</time_frame>
    <description>Rey Auditory Verbal Learning Test (RAVLT) immediate recall accuracy scores will be used to measure verbal memory. Scores will be compared between groups. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-square, Kruskal-Wallis, and analysis of variance (ANOVA) will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of delayed memory</measure>
    <time_frame>March 2025</time_frame>
    <description>RAVLT 20 minute recall accuracy scores, will be used to measure delayed memory and will be compared between groups. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-square, Kruskal-Wallis, and analysis of variance (ANOVA) will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of working memory</measure>
    <time_frame>March 2025</time_frame>
    <description>Letter-Number Sequencing subtest from the Wechsler Memory Scale III scores will be used to measure working memory and will be compared between groups. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-square, Kruskal-Wallis, and analysis of variance (ANOVA) will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of cognitive flexibility using trail making tasks</measure>
    <time_frame>March 2025</time_frame>
    <description>Delis-Kaplan Executive Function System (DKEFS),Trail Making Task scores will be used to assess the cognitive flexibility component of executive function. Scores are derived from time to complete the task plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of multitasking</measure>
    <time_frame>March 2025</time_frame>
    <description>DKEFS Trail Making Task scores will be used to assess the multitasking component of executive function. Scores are derived from time to complete the task, plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of cognitive flexibility using color-word inference test</measure>
    <time_frame>March 2025</time_frame>
    <description>DKEFS Color-Word Interference Test (CWIT) scores will be used to measure the cognitive flexibility component of executive function. The CWIT is scored by time to complete plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of inhibition</measure>
    <time_frame>March 2025</time_frame>
    <description>DKEFS CWIT scores will be used to measure the inhibition component of executive function. The CWIT is scored by time to complete plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of verbal ability cognitive control</measure>
    <time_frame>March 2025</time_frame>
    <description>DKEFS Verbal Fluency Task will be used to assess the verbal functioning cognitive control ability component of executive function. Scores are derived from the number of unique, correct words. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of psychomotor speed</measure>
    <time_frame>March 2025</time_frame>
    <description>The Grooved Peg Board test will be used to assess psychomotor speed. It is scored according to time for completion combined with the number of dropped pegs. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Hypoglycemia</condition>
  <condition>Cognition</condition>
  <arm_group>
    <arm_group_label>Hypoglycemia after upper gastrointestinal (GI) surgery</arm_group_label>
    <description>Participants with hypoglycemia after upper GI surgery, recruited from the Joslin Hypoglycemia Clinic and from other hypoglycemia studies at Joslin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Asymptomatic post-bariatric participants</arm_group_label>
    <description>Participants with a history of bariatric surgery, but without a diagnosis of hypoglycemia, or symptoms of hypoglycemia. They will be recruited by advertisement flyers at postoperative surgical clinics at local hospitals (e.g. Brigham and Women's and Beth Israel Deaconess Hospitals) and from other hypoglycemia studies at Joslin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hypoglycemia no upper GI surgery &amp; no diabetes (DM) or pre-DM</arm_group_label>
    <description>Participants with hypoglycemia and no history of upper gastrointestinal surgery, and NO current diagnosis of diabetes or pre-diabetes, recruited from the Joslin Hypoglycemia Clinic, or from other hypoglycemia studies at Joslin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls, no hypoglycemia or history of upper GI surgery</arm_group_label>
    <description>Participants without hypoglycemia or upper gastrointestinal surgery (controls), recruited by local advertisement. Some participants may be recruited from other hypoglycemia studies at Joslin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cognitive Assessment (not diagnostic)</intervention_name>
    <description>Cognitive testing will assess working memory and attention, verbal memory and delayed memory, executive function, and psychomotor speed.</description>
    <arm_group_label>Asymptomatic post-bariatric participants</arm_group_label>
    <arm_group_label>Controls, no hypoglycemia or history of upper GI surgery</arm_group_label>
    <arm_group_label>Hypoglycemia after upper gastrointestinal (GI) surgery</arm_group_label>
    <arm_group_label>Hypoglycemia no upper GI surgery &amp; no diabetes (DM) or pre-DM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>ECG</intervention_name>
    <description>ECG will take place during screening visit.</description>
    <arm_group_label>Asymptomatic post-bariatric participants</arm_group_label>
    <arm_group_label>Controls, no hypoglycemia or history of upper GI surgery</arm_group_label>
    <arm_group_label>Hypoglycemia after upper gastrointestinal (GI) surgery</arm_group_label>
    <arm_group_label>Hypoglycemia no upper GI surgery &amp; no diabetes (DM) or pre-DM</arm_group_label>
    <other_name>Electrocardiogram (ECG)</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Participants will be recruited into 4 groups: (1) patients with hypoglycemia after upper&#xD;
        gastrointestinal surgery, recruited from the Joslin Hypoglycemia Clinic, (2) asymptomatic&#xD;
        post-bariatric patients, recruited from postoperative surgical clinics at Brigham and&#xD;
        Women's Hospital, (3) patients with hypoglycemia and no history of upper gastrointestinal&#xD;
        surgery, and no current diagnosis of diabetes or pre-diabetes, recruited from the Joslin&#xD;
        Hypoglycemia Clinic, (4) participants without hypoglycemia or upper gastrointestinal&#xD;
        surgery (controls), recruited by local advertisement.&#xD;
&#xD;
        Some participants may be recruited from other hypoglycemia studies at Joslin.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-70 years of age, inclusive, at screening.&#xD;
&#xD;
          2. Willingness to provide informed consent and attend one study visit.&#xD;
&#xD;
          3. For hypoglycemia after upper GI surgery group: Males or females diagnosed with ongoing&#xD;
             post upper GI surgery hypoglycemia, with prior episodes of neuroglycopenia,&#xD;
             unresponsive to dietary intervention.&#xD;
&#xD;
          4. For hypoglycemia without a history of upper gastrointestinal surgery group: Males or&#xD;
             females diagnosed with ongoing hypoglycemia with prior episodes of neuroglycopenia,&#xD;
             and without a history of prediabetes, diabetes, or upper GI surgery.&#xD;
&#xD;
          5. For post-bariatric without hypoglycemia group: Males or females with history of&#xD;
             bariatric surgery, and no history of symptomatic hypoglycemia.&#xD;
&#xD;
          6. For non-surgical controls only: Males or females with no history of upper GI surgery&#xD;
             and no history of hypoglycemia, prediabetes, or diabetes.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Active treatment with any diabetes medications, except for acarbose.&#xD;
&#xD;
          2. History of cerebrovascular accident.&#xD;
&#xD;
          3. History of a traumatic brain injury not related to hypoglycemia.&#xD;
&#xD;
          4. Active depression.&#xD;
&#xD;
          5. Active alcohol abuse or substance abuse.&#xD;
&#xD;
          6. Known insulinoma, gastrinoma or other neuroendocrine tumor.&#xD;
&#xD;
          7. Having undergone same / similar cognitive assessments within the last calendar year.&#xD;
&#xD;
        There will be no involvement of special vulnerable populations such as fetuses, neonates,&#xD;
        pregnant women, children, prisoners, institutionalized or incarcerated individuals, or&#xD;
        others who may be considered vulnerable populations.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Mary Elizabeth Patti, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Joslin Diabetes Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Joslin Diabetes Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>February 8, 2023</last_update_submitted>
  <last_update_submitted_qc>February 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Executive Function</keyword>
  <keyword>Memory</keyword>
  <keyword>Post-Bariatric Hypoglycemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoglycemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 21, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04430582
org study id: 00000098
nct id: NCT04430582
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine if there is a relationship between recurrent
      hypoglycemia (low blood sugar) and cognition (thinking) in individuals who have a history of
      hypoglycemia, but do not have pre-diabetes or diabetes.

      This study will analyze whether recurrent hypoglycemia is associated with differences in
      cognition (thinking), and if individuals with a history of hypoglycemia perform less well on
      cognitive assessments compared to individuals without known hypoglycemia.
This study will test the hypothesis that recurrent hypoglycemia is associated with
      differences in cognition (thinking), by analyzing results of cognitive testing in individuals
      with a history of hypoglycemia as compared with those without known hypoglycemia.

      This pilot study will identify cognitive domains of interest in participants with
      hypoglycemia, as well as inform the development of a future battery of assessments, which
      could be replicated in a larger sample. Cognitive domains which will be assessed include:
      memory, language, executive function, and psychomotor speed.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Assessment of verbal memory
time frame: March 2025
description: Rey Auditory Verbal Learning Test (RAVLT) immediate recall accuracy scores will be used to measure verbal memory. Scores will be compared between groups. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-square, Kruskal-Wallis, and analysis of variance (ANOVA) will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.
measure: Assessment of delayed memory
time frame: March 2025
description: RAVLT 20 minute recall accuracy scores, will be used to measure delayed memory and will be compared between groups. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-square, Kruskal-Wallis, and analysis of variance (ANOVA) will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.
measure: Assessment of working memory
time frame: March 2025
description: Letter-Number Sequencing subtest from the Wechsler Memory Scale III scores will be used to measure working memory and will be compared between groups. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-square, Kruskal-Wallis, and analysis of variance (ANOVA) will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.
measure: Assessment of cognitive flexibility using trail making tasks
time frame: March 2025
description: Delis-Kaplan Executive Function System (DKEFS),Trail Making Task scores will be used to assess the cognitive flexibility component of executive function. Scores are derived from time to complete the task plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.
measure: Assessment of multitasking
time frame: March 2025
description: DKEFS Trail Making Task scores will be used to assess the multitasking component of executive function. Scores are derived from time to complete the task, plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.
measure: Assessment of cognitive flexibility using color-word inference test
time frame: March 2025
description: DKEFS Color-Word Interference Test (CWIT) scores will be used to measure the cognitive flexibility component of executive function. The CWIT is scored by time to complete plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.
measure: Assessment of inhibition
time frame: March 2025
description: DKEFS CWIT scores will be used to measure the inhibition component of executive function. The CWIT is scored by time to complete plus errors. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.
measure: Assessment of verbal ability cognitive control
time frame: March 2025
description: DKEFS Verbal Fluency Task will be used to assess the verbal functioning cognitive control ability component of executive function. Scores are derived from the number of unique, correct words. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.
measure: Assessment of psychomotor speed
time frame: March 2025
description: The Grooved Peg Board test will be used to assess psychomotor speed. It is scored according to time for completion combined with the number of dropped pegs. Distributions of relevant variables will be examined for outliers and to determine appropriate statistics for use. Chi-squared, Kruskal-Wallis, and ANOVA tests will be used to examine differences between groups. Linear models may be constructed to adjust for covariates and for effect modification.
arm group label: Hypoglycemia after upper gastrointestinal (GI) surgery
description: Participants with hypoglycemia after upper GI surgery, recruited from the Joslin Hypoglycemia Clinic and from other hypoglycemia studies at Joslin.
arm group label: Asymptomatic post-bariatric participants
description: Participants with a history of bariatric surgery, but without a diagnosis of hypoglycemia, or symptoms of hypoglycemia. They will be recruited by advertisement flyers at postoperative surgical clinics at local hospitals (e.g. Brigham and Women's and Beth Israel Deaconess Hospitals) and from other hypoglycemia studies at Joslin.
arm group label: Hypoglycemia no upper GI surgery & no diabetes (DM) or pre-DM
description: Participants with hypoglycemia and no history of upper gastrointestinal surgery, and NO current diagnosis of diabetes or pre-diabetes, recruited from the Joslin Hypoglycemia Clinic, or from other hypoglycemia studies at Joslin.
arm group label: Controls, no hypoglycemia or history of upper GI surgery
description: Participants without hypoglycemia or upper gastrointestinal surgery (controls), recruited by local advertisement. Some participants may be recruited from other hypoglycemia studies at Joslin.
intervention type: Other
intervention name: Cognitive Assessment (not diagnostic)
description: Cognitive testing will assess working memory and attention, verbal memory and delayed memory, executive function, and psychomotor speed.
arm group label: Asymptomatic post-bariatric participants
arm group label: Controls, no hypoglycemia or history of upper GI surgery
arm group label: Hypoglycemia after upper gastrointestinal (GI) surgery
arm group label: Hypoglycemia no upper GI surgery & no diabetes (DM) or pre-DM
intervention type: Diagnostic Test
intervention name: ECG
description: ECG will take place during screening visit.
arm group label: Asymptomatic post-bariatric participants
arm group label: Controls, no hypoglycemia or history of upper GI surgery
arm group label: Hypoglycemia after upper gastrointestinal (GI) surgery
arm group label: Hypoglycemia no upper GI surgery & no diabetes (DM) or pre-DM
other name: Electrocardiogram (ECG)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
last name: Mary Elizabeth Patti, MD
role: Principal Investigator
affiliation: Joslin Diabetes Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hypoglycemia
sharing ipd: No
submitted: June 21, 2023