<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/NCT02193425</url>
  </required_header>
  <id_info>
    <org_study_id>140144</org_study_id>
    <secondary_id>14-AA-0144</secondary_id>
    <nct_id>NCT02193425</nct_id>
  </id_info>
  <brief_title>Reliability of the Human Brain Connectome</brief_title>
  <official_title>Reliability Of The Human Brain Connectome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - Magnetic resonance imaging (MRI) is used to investigate brain function. Researchers want to&#xD;
      use MRI to better understand the function patterns and connections between brain regions in&#xD;
      healthy people. This might help people with brain diseases in the future.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        -  To evaluate MRI methods performed twice on the same day.&#xD;
&#xD;
        -  To evaluate brain function using positron emission tomography (PET).&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Healthy volunteers at least 18 years old.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Visit 1:&#xD;
&#xD;
        -  Participants will be screened with medical history, physical exam, and interview about&#xD;
           drug and alcohol use and psychiatric history.&#xD;
&#xD;
        -  They will give blood and urine samples. Their breath will be tested for alcohol and&#xD;
           smoking.&#xD;
&#xD;
        -  Visit 2:&#xD;
&#xD;
        -  Participants will have urine collected. They will have MRI scans, some while resting,&#xD;
           some while doing tasks on a computer.&#xD;
&#xD;
        -  The MRI scanner is a metal cylinder in a strong magnetic field. Participants will lie on&#xD;
           a table that slides in and out of the cylinder, with a coil over their head.&#xD;
           Participants will get earplugs for loud noises.&#xD;
&#xD;
        -  Visit 3:&#xD;
&#xD;
        -  Participants will have urine collected.&#xD;
&#xD;
        -  A needle will guide a thin plastic tube (catheter) into each arm. The needle will be&#xD;
           removed, leaving the catheter in the vein.&#xD;
&#xD;
        -  Participants will then have a PET scan. They will get the chemical 18FDG in the&#xD;
           catheter. They will lie on a bed that slides in and out of the PET scanner, with a cap&#xD;
           on their head.&#xD;
&#xD;
        -  Participants may have tests of memory, attention, concentration, and thinking. They may&#xD;
           complete interviews, questionnaires, tests on paper or computer, and simple actions.&#xD;
&#xD;
        -  Participants will wear a device for 1 week between visits to measure activity and sleep.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pr(SqrRoot)(Copyright)cis:&#xD;
&#xD;
      Objectives: The overarching goal of this study is to quantify the reproducibility of multiple&#xD;
      measures of brain functional connectivity (FC) during resting conditions and during task&#xD;
      performance. Secondary objectives are to assess the dynamic properties and energy&#xD;
      requirements of the human brain connectome as well as the effects of physiologic noise,&#xD;
      gender and aging on measures of brain functional connectivity at rest and during task&#xD;
      performance.&#xD;
&#xD;
      Study population: 60 healthy males and 60 healthy females 18 years or older will be included.&#xD;
&#xD;
      Design: Participants will undergo two MRI/MRS sessions to evaluate test-retest reliability of&#xD;
      FC at rest as well as during task performance, and one 18F-Fluorodeoxyglucose (FDG)-PET&#xD;
      session to assess the association between FC and glucose metabolism in the human brain.&#xD;
&#xD;
      Outcome parameters: The variability of the gender and aging effects on FC measures (lFCD, L,&#xD;
      C, and S) collected in RS and TS conditions , which will be quantified using volxelwise ICC&#xD;
      (3,1). The variability of brain metabolite concentrations in precuneus.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 8, 2015</start_date>
  <completion_date type="Actual">May 23, 2023</completion_date>
  <primary_completion_date type="Actual">May 23, 2023</primary_completion_date>
  <phase>Early 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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The overarching goal of this study is to quantify the reproducibility of multiple measures of brain functional connectivity (FC) during resting conditions and during task performance.</measure>
    <time_frame>end of study</time_frame>
    <description>The test-retest reproducibility of the gender and aging effects on FC measures (lFCD, C, L and S) acquired in RS and TS conditions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The correlation between glucose metabolism, CBF, lFCD, C, L and S and its contribution to between- subjects FC-variability during RS.</measure>
    <time_frame>end of study</time_frame>
    <description>To assess the dynamic properties and energy requirements of the human brain connectome as well as the effects of physiologic noise, gender and aging on measures of brain functional connectivity at rest and during task performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The association between IFCD and the underlying structural connectivity and its contribution to between- subjects FC-variability during RS.</measure>
    <time_frame>end of study</time_frame>
    <description>To assess the dynamic properties and energy requirements of the human brain connectome as well as the effects of physiologic noise, gender and aging on measures of brain functional connectivity at rest and during task performance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The correlation between physiologic noise and FC measures (lFCD, C, L and S) and its contribution to within- subjects FC-variability during RS and TS conditions.</measure>
    <time_frame>end of study</time_frame>
    <description>To assess the dynamic properties and energy requirements of the human brain connectome as well as the effects of physiologic noise, gender and aging on measures of brain functional connectivity at rest and during task performance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The dynamics of the FC measures (lFCD, C, L and S) and its contribution to within- subjects FC-variability during RS and TS conditions.</measure>
    <time_frame>end of study</time_frame>
    <description>To assess the dynamic properties and energy requirements of the human brain connectome as well as the effects of physiologic noise, gender and aging on measures of brain functional connectivity at rest and during task performance</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">112</enrollment>
  <condition>Normal Physiology</condition>
  <arm_group>
    <arm_group_label>PET FDG &amp;amp; MRI Scans</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The test-retest reproducibility of the gender and aging effects on FC measures (lFCD, C, L and S) acquired in RS and TS conditions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>F-18FDG</intervention_name>
    <description>18F-Fluorodeoxyglucose (FDG)-PET session to assess the association between functional connectivity (FC) and glucose metabolism in the human brain.</description>
    <arm_group_label>PET FDG &amp;amp; MRI Scans</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRI</intervention_name>
    <description>Two MRI/MRS sessions to evaluate test-retest reliability of functional connectivity (FC) at rest as well as during task performance.</description>
    <arm_group_label>PET FDG &amp;amp; MRI Scans</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
        All Participants:&#xD;
&#xD;
          -  Older than 18 years of age.&#xD;
&#xD;
          -  Ability to provide written informed consent as determined by physical examination and&#xD;
             verbal communication. Capacity to consent will be determined by those obtaining the&#xD;
             informed consent&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Pregnant or breast feeding. Females of childbearing potential must have negative urine&#xD;
             pregnancy test and not be currently breastfeeding. Post-menopausal or surgically&#xD;
             sterile (tubal ligation or hysterectomy) females satisfy these criteria.&#xD;
&#xD;
          -  The following current chronically used (within 2 months of study procedures)&#xD;
             psychoactive medications or medications that can affect brain function (including but&#xD;
             not limited to meperidine, tricyclic antidpressants, selective serotonin reuptake&#xD;
             inhibitors (SSRIs), or serotonin norepinephrine reuptake inhibitors (SNRIs), stimulant&#xD;
             or stimulant-like medications (amphetamine, methylphenidate, modafinil); opioid&#xD;
             analgesics; antianginal agents; antiarrhythmics; systemic corticosteroids;&#xD;
             anticholinergics; anticoagulants; anticonvulsants; antihistamines (sedating); beta&#xD;
             blocker antihypertensives; antineoplastics; antiobesity; antipsychotics; anxiolytics&#xD;
&#xD;
        (benzodiazepine or barbiturates); lithium; muscle relaxants, and systemic steroids as&#xD;
        determined by history and clinical exam.&#xD;
&#xD;
          -  Current or past DSM-IV or DSM-5 diagnosis of a psychiatric disorder as determined by&#xD;
             history and clinical exam including substance use disorder (except for&#xD;
             nicotine/caffeine), alcoholism and alcohol dependence. Past history of a mental&#xD;
             disorder as defined by DSM-IV or DSM-5 will be excluded only if it required&#xD;
             hospitalization (any length), or chronic medication management (more than 4 weeks),&#xD;
             and that could impact brain function at the time of the study.&#xD;
&#xD;
          -  Those with a binge drinking history every month continuously for the last 10 years&#xD;
             will also be excluded. Binge drinkers are those who being female consume 4 or more&#xD;
             drinks and males consume 5 or more drinks in one occasion at least once a month.&#xD;
&#xD;
          -  Major medical problems that can impact brain function at the time of the scan&#xD;
             (including but not limited to HIV; central nervous system including seizures and&#xD;
             psychosis; cardiovascular including hypertension and arrhythmias; metabolic,&#xD;
             autoimmune, endocrine) as determined by history and clinical exam. Participants aged&#xD;
             60 and older with any medical problems that are controlled will not be excluded.&#xD;
&#xD;
          -  Any clinically significant laboratory finding as determined during the screening&#xD;
             procedures.&#xD;
&#xD;
          -  Have had previous radiation exposure (from X-rays, PET scans, or other exposure) that,&#xD;
             with the exposure from this study, would exceed NIH annual research limits.&#xD;
&#xD;
          -  Head trauma with loss of consciousness for more than 30 minutes.&#xD;
&#xD;
          -  Presence of ferromagnetic objects in the body that are contraindicated for MRI/MRS of&#xD;
             the head (pacemakers or other implanted electrical devices, brain stimulators, some&#xD;
             types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner,&#xD;
             implanted delivery pump, or shrapnel fragments), fear of enclosed spaces, or other&#xD;
             standard contraindication to MRI/MRS (self-report checklist).&#xD;
&#xD;
          -  Cannot lie comfortably flat on back for up to 2 hours in the PET and MRI/MRS scanners.&#xD;
&#xD;
          -  Body weight &gt; 250 kg. This is the upper limit that the bed of the MR scanner can&#xD;
             accommodate.&#xD;
&#xD;
          -  NIH employees who are study investigators, as well as their superiors, subordinates&#xD;
             and immediate family members (adult children, spouses, parents, siblings).&#xD;
&#xD;
          -  Non-English speakers (subjects must be able to read and comprehend English).&#xD;
&#xD;
               -  Subjects will not be excluded from enrollment onto this study if their urine test&#xD;
                  is positive for drugs. However, if they test positive on scheduled study&#xD;
                  procedure days involving study imaging (MRI/MRS and PET) and Neuropsychological&#xD;
                  testing, the procedures will be postponed and rescheduled. We will allow for up&#xD;
                  to 3 rescheduled study days that were the result of positive urine drug screens.&#xD;
                  If the drug test is positive on the third rescheduled visit, the participant will&#xD;
                  be withdrawn from the study.&#xD;
&#xD;
        The intent of the research has no prospect of direct benefit to the subject. Therefore, we&#xD;
        are excluding non-English speakers in this research study since it includes the&#xD;
        administration of questionnaires, surveys and assessments that are validated for English,&#xD;
        although some are available in Spanish.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dardo G Tomasi, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2014-AA-0144.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>May 23, 2023</verification_date>
  <study_first_submitted>July 16, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <last_update_submitted>July 19, 2023</last_update_submitted>
  <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>fMRI</keyword>
  <keyword>Brain Connectivity</keyword>
  <keyword>PET</keyword>
  <keyword>18FDG</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluorodeoxyglucose F18</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>.Data is analyzed in groups so no individual information will be shared.</ipd_description>
  </patient_data>
  <!-- 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/NCT02193425
org study id: 140144
secondary id: 14-AA-0144
nct id: NCT02193425
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      - Magnetic resonance imaging (MRI) is used to investigate brain function. Researchers want to
      use MRI to better understand the function patterns and connections between brain regions in
      healthy people. This might help people with brain diseases in the future.

      Objectives:

        -  To evaluate MRI methods performed twice on the same day.

        -  To evaluate brain function using positron emission tomography (PET).

      Eligibility:

      - Healthy volunteers at least 18 years old.

      Design:

        -  Visit 1:

        -  Participants will be screened with medical history, physical exam, and interview about
           drug and alcohol use and psychiatric history.

        -  They will give blood and urine samples. Their breath will be tested for alcohol and
           smoking.

        -  Visit 2:

        -  Participants will have urine collected. They will have MRI scans, some while resting,
           some while doing tasks on a computer.

        -  The MRI scanner is a metal cylinder in a strong magnetic field. Participants will lie on
           a table that slides in and out of the cylinder, with a coil over their head.
           Participants will get earplugs for loud noises.

        -  Visit 3:

        -  Participants will have urine collected.

        -  A needle will guide a thin plastic tube (catheter) into each arm. The needle will be
           removed, leaving the catheter in the vein.

        -  Participants will then have a PET scan. They will get the chemical 18FDG in the
           catheter. They will lie on a bed that slides in and out of the PET scanner, with a cap
           on their head.

        -  Participants may have tests of memory, attention, concentration, and thinking. They may
           complete interviews, questionnaires, tests on paper or computer, and simple actions.

        -  Participants will wear a device for 1 week between visits to measure activity and sleep.
Pr(SqrRoot)(Copyright)cis:

      Objectives: The overarching goal of this study is to quantify the reproducibility of multiple
      measures of brain functional connectivity (FC) during resting conditions and during task
      performance. Secondary objectives are to assess the dynamic properties and energy
      requirements of the human brain connectome as well as the effects of physiologic noise,
      gender and aging on measures of brain functional connectivity at rest and during task
      performance.

      Study population: 60 healthy males and 60 healthy females 18 years or older will be included.

      Design: Participants will undergo two MRI/MRS sessions to evaluate test-retest reliability of
      FC at rest as well as during task performance, and one 18F-Fluorodeoxyglucose (FDG)-PET
      session to assess the association between FC and glucose metabolism in the human brain.

      Outcome parameters: The variability of the gender and aging effects on FC measures (lFCD, L,
      C, and S) collected in RS and TS conditions , which will be quantified using volxelwise ICC
      (3,1). The variability of brain metabolite concentrations in precuneus.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: The overarching goal of this study is to quantify the reproducibility of multiple measures of brain functional connectivity (FC) during resting conditions and during task performance.
time frame: end of study
description: The test-retest reproducibility of the gender and aging effects on FC measures (lFCD, C, L and S) acquired in RS and TS conditions.
measure: The correlation between glucose metabolism, CBF, lFCD, C, L and S and its contribution to between- subjects FC-variability during RS.
time frame: end of study
description: To assess the dynamic properties and energy requirements of the human brain connectome as well as the effects of physiologic noise, gender and aging on measures of brain functional connectivity at rest and during task performance.
measure: The association between IFCD and the underlying structural connectivity and its contribution to between- subjects FC-variability during RS.
time frame: end of study
description: To assess the dynamic properties and energy requirements of the human brain connectome as well as the effects of physiologic noise, gender and aging on measures of brain functional connectivity at rest and during task performance
measure: The correlation between physiologic noise and FC measures (lFCD, C, L and S) and its contribution to within- subjects FC-variability during RS and TS conditions.
time frame: end of study
description: To assess the dynamic properties and energy requirements of the human brain connectome as well as the effects of physiologic noise, gender and aging on measures of brain functional connectivity at rest and during task performance
measure: The dynamics of the FC measures (lFCD, C, L and S) and its contribution to within- subjects FC-variability during RS and TS conditions.
time frame: end of study
description: To assess the dynamic properties and energy requirements of the human brain connectome as well as the effects of physiologic noise, gender and aging on measures of brain functional connectivity at rest and during task performance
arm group label: PET FDG &amp; MRI Scans
arm group type: Experimental
description: The test-retest reproducibility of the gender and aging effects on FC measures (lFCD, C, L and S) acquired in RS and TS conditions.
intervention type: Drug
intervention name: F-18FDG
description: 18F-Fluorodeoxyglucose (FDG)-PET session to assess the association between functional connectivity (FC) and glucose metabolism in the human brain.
arm group label: PET FDG &amp; MRI Scans
intervention type: Device
intervention name: MRI
description: Two MRI/MRS sessions to evaluate test-retest reliability of functional connectivity (FC) at rest as well as during task performance.
arm group label: PET FDG &amp; MRI Scans
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Dardo G Tomasi, Ph.D.
role: Principal Investigator
affiliation: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2014-AA-0144.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Fluorodeoxyglucose F18
sharing ipd: No
ipd description: .Data is analyzed in groups so no individual information will be shared.