<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/NCT03234530</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 16-0899</org_study_id>
    <secondary_id>U01OH011326-01A1</secondary_id>
    <nct_id>NCT03234530</nct_id>
  </id_info>
  <brief_title>World Trade Center Kidney-Link</brief_title>
  <official_title>Linking the Effects of 9/11 to Kidney Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Centers for Disease Control and Prevention</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute for Occupational Safety and Health (NIOSH/CDC)</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</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>
      This study focuses on the prevalence and identification of kidney disease among participants&#xD;
      of the WTC Health Program and the study team are planning to assess kidney disease in a&#xD;
      multi-factorial manner. The first aim of this study is to correlate kidney dysfunction with&#xD;
      9/11 exposure, and the study team predicts that exposure to 9/11 is an independent risk&#xD;
      factor in kidney disease among the WTC Health Program participants. Secondly, the study team&#xD;
      proposes that a well-established WTC-related condition, obstructive sleep apnea (OSA), is&#xD;
      independently associated with kidney disease. In addition, the study team believe there is a&#xD;
      temporal causative relationship between evidence of kidney disease and the severity of OSA.&#xD;
      Finally, the last aim is to further identify and explore potential mechanisms and phenotypes&#xD;
      of kidney disease in participants of the WTC Health Programs.&#xD;
&#xD;
      Regardless of whether the analyses support or reject these hypotheses, the findings will be&#xD;
      of equally great public health importance. Successful completion of the proposed research&#xD;
      would address a critical knowledge gap regarding the risk of kidney damage among this group&#xD;
      of patients, and would inform future mechanistic studies with the potential to impact&#xD;
      prevention.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Exposure to environmental toxins results in significant long-term health effects in workers.&#xD;
      More than 91,000 rescue and recovery workers and volunteers at the World Trade Center (WTC)&#xD;
      sustained exposure to thousands of tons of coarse and fine particulate matter. Thousands of&#xD;
      responders are currently treated for WTC-related health conditions or may be at risk for&#xD;
      worsening health. Toxic effects of particulate matter are known to affect the pulmonary,&#xD;
      renal and cardiovascular systems. The specific effects of the exposure to 9/11 are partly&#xD;
      known, and require further investigation, as outlined in the Zadroga Act (Public Law111-347).&#xD;
&#xD;
      This study builds on the preliminary data to address a critical knowledge gap about the risk&#xD;
      of kidney damage among WTC responders, the progression of kidney decline since exposure, and&#xD;
      the association of kidney disease with a defined WTC-related diagnosis, obstructive sleep&#xD;
      apnea (OSA). Successful completion of the proposed research would address a critical&#xD;
      knowledge gap regarding the risk of kidney damage and the relationship to important chronic&#xD;
      diseases (OSA and immune-mediated disease) among WTC participants, and would inform future&#xD;
      mechanistic studies with the potential to impact disease prevention.&#xD;
&#xD;
      Specific Aim 1: To quantify the risk of kidney damage and the relationship to 9/11 exposure&#xD;
      among WTC Health Program participants. Currently, the cohort of 406 first responders&#xD;
      represents the sole dedicated evaluation of kidney disease in WTC Health Program&#xD;
      participants. The study team will test the hypothesis that exposure to 9/11 is independently&#xD;
      associated with kidney disease and enrich the enrollment of the current study population with&#xD;
      a diversified population including categories of workers who have not been enrolled, as well&#xD;
      as a control group of urban workers (NYC) not exposed to the dust from the WTC.&#xD;
&#xD;
      Aim 1a. The study team hypothesize that albuminuria and decreased estimated glomerular&#xD;
      filtration rate (eGFR) will occur more frequently in WTC responders than in the general&#xD;
      population and will correlate with the degree of exposure as defined by the previously&#xD;
      defined WTC exposure score (adjusting for demographics, family history of chronic kidney&#xD;
      disease (CKD), and diagnosed, treated or laboratory confirmed diabetes and hypertension). The&#xD;
      study team will also assess established urine biomarkers of proximal tubular injury,&#xD;
      including β2-M, Kidney Injury Molecule-1 (KIM-1), and Interleukin 18 (IL-18), as well as&#xD;
      markers of distal tubular function, Loop of Henle function, and tubulointerstitial&#xD;
      inflammation.&#xD;
&#xD;
      Aim 1b. The study team hypothesize that initial exposure to 9/11 contributed to reduction in&#xD;
      renal function over time. The study team will quantify change in renal function over time by&#xD;
      analyzing eGFR at WTC Health Program Visit 1 (V1) and subsequent visits, adjusting for known&#xD;
      co-morbid conditions.&#xD;
&#xD;
      Aim 1c. The study team will create a repository of WTC responders with established kidney&#xD;
      disease (including relatively rare disease) to qualitatively evaluate and describe the&#xD;
      spectrum of kidney disease in the entire WTC population and compare to patterns of kidney&#xD;
      disease in the general population. The study team will actively enlist those with a verified&#xD;
      physician diagnosis of kidney disease, and collect biopsy reports and slides for review.&#xD;
&#xD;
      Specific Aim 2: Evaluate the association of kidney disease and the established WTC-related&#xD;
      condition, OSA.&#xD;
&#xD;
      Aim 2a. OSA is particularly prevalent among WTC cohorts. The study team hypothesize that&#xD;
      there is an independent association between prevalent OSA and prevalent kidney disease.&#xD;
&#xD;
      Aim2b. The study team hypothesize that OSA independently contributes to the progression of&#xD;
      kidney disease. The study team will assess the temporal relationship of eGFR decline to the&#xD;
      presence and severity of OSA, using longitudinal data from the WTC data center.&#xD;
&#xD;
      Specific Aim 3: To evaluate potential mechanisms of kidney injury in WTC Health Program&#xD;
      participants.&#xD;
&#xD;
      Aim3a. In order to understand the role of chronic inflammation, the study team will evaluate&#xD;
      established inflammatory markers which have been implicated as potential mediators of both&#xD;
      OSA and CKD, including IL-10, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, IL-12p70.,&#xD;
      high sensitivity C-reactive protein (hs-CRP), and white blood cell count (WBC).&#xD;
&#xD;
      Aim3b. Based on the preliminary data noting increases in heavy metal levels in urine and&#xD;
      blood, the study team will narrow the focus to evaluate the role of cadmium and lead in the&#xD;
      development of kidney disease with evaluations of lead content in bone (marker of long-term&#xD;
      exposure) as well as in blood. Since study participants include law enforcement personnel&#xD;
      (with known exposure to lead), the characterization of bone lead levels will have an&#xD;
      important health impact, whether or not a relationship to 9/11 is detected.&#xD;
&#xD;
      Aim3c. In a registry cohort of WTC responders with established kidney disease the study team&#xD;
      will explore potential mechanisms as determined by the observed patterns of disease by&#xD;
      developing a comprehensive repository of data on WTC Health Program participants with common&#xD;
      and rare kidney diseases, the study team will define specific clinical profiles and identify&#xD;
      potential mechanisms that warrant future study. Importantly, the study team will develop a&#xD;
      process across all WTC Health Programs (inclusive of approximately 50,000 individuals), to&#xD;
      monitor those with early kidney disease as well as those with biopsy-proven kidney disease,&#xD;
      at any stage.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2017</start_date>
  <completion_date type="Actual">June 1, 2021</completion_date>
  <primary_completion_date type="Actual">June 1, 2021</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>glomerular filtration rate (eGFR)</measure>
    <time_frame>day 1</time_frame>
    <description>eGFR will be calculated using the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equations. The proposed studies will evaluate differences in the combined creatinine-cystatin C eGFR, which provides the most accurate estimate of GFR, and the creatinine-based CKD-EPI eGFR, which is more practical for use in clinical practice and in monitoring programs. Values &gt; 200 will be set to 200mL/min/1.73m2</description>
  </primary_outcome>
  <primary_outcome>
    <measure>albuminuria</measure>
    <time_frame>day 1</time_frame>
    <description>albumin level in urine</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Berlin questionnaire</measure>
    <time_frame>day 1</time_frame>
    <description>Those who are not diagnosed with sleep apnea will be assessed for risk of developing sleep apnea using the Berlin questionnaire. It includes 11 questions organized into three categories, 5 questions related to snoring and the cessation of breathing in category 1, 4 questions related to daytime sleepiness in category 2, 1 question about high blood pressure, and 1 question regarding BMI in category 3. When two of three categories are classified as positive for a patient, the patient is rated as being at high risk of having OSA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>apnea-hypopnea index (AHI)</measure>
    <time_frame>day 1</time_frame>
    <description>Those at high risk for sleep apnea will undergo home sleep a study test to determine apnea hypopnea index (AHI).&#xD;
Those diagnosed with sleep apnea, latest sleep study will be used to obtain AHI. To determine AHI, add the total number of apnea events, plus hypopnea events and divide by the total number of minutes of actual sleep time, then multiply by 60. AHI - Apnea Hypopnea Index - The # of apneas and hypopneas per hour.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">555</enrollment>
  <condition>Chronic Kidney Diseases</condition>
  <condition>Obstructive Sleep Apnea</condition>
  <arm_group>
    <arm_group_label>WTC responders</arm_group_label>
    <description>WTC Health Program participants</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Urban workers</arm_group_label>
    <description>Control group of urban workers in NYC not exposed to the dust from the WTC</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum, plasma, urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        World Trade Center rescue and recovery workers and volunteers who are enrolled or being&#xD;
        seen in any WTC Clinical Centers of Excellence&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Exposed Group: - Adult patients (35 to 75 years)&#xD;
&#xD;
          -  Enrolled or was seen at any of the WTC Clinical Centers of Excellence&#xD;
&#xD;
        Unexposed Group: - Adult patients (35 to 75 years)&#xD;
&#xD;
          -  Lived or worked in NYC at least 10 years since 9/11/01 but were not exposed to the the&#xD;
             dust at Ground Zero (not living in proximity of Ground Zero, nor involved in the&#xD;
             rescue and recovery at Ground Zero&#xD;
&#xD;
        Registry Part: - Adult patient (18 to 75 years)&#xD;
&#xD;
          -  Enrolled or was seen at any of the WTC Clinical Centers of Excellence or WTC&#xD;
             Environmental Health Centers&#xD;
&#xD;
          -  With a diagnosis of any Kidney Injury or disease after 9/11/01&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients below 18 years of age&#xD;
&#xD;
          -  Individuals with an occupation involving chronic exposure to inhaled particulate&#xD;
             matter (e.g. iron/steel workers and sand hog workers)&#xD;
&#xD;
          -  For the registry part, patients with kidney disease prior to 9/11/01&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mary Ann McLaughlin, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <last_update_submitted>June 8, 2021</last_update_submitted>
  <last_update_submitted_qc>June 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Icahn School of Medicine at Mount Sinai</investigator_affiliation>
    <investigator_full_name>Maryann Mclaughlin</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>albuminuria</keyword>
  <keyword>sleep apnea</keyword>
  <keyword>particulate matter</keyword>
  <keyword>renal injury</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Sleep Apnea, Obstructive</mesh_term>
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The final research data will be a computerized dataset and includes self-reported demographic and medical data, responses from standard questionnaires, as well as results of laboratory tests (urine and blood samples) . Even though the final dataset will be stripped of identifiers prior to release for sharing, we believe that there remains the possibility of deductive disclosure of subjects with unusual characteristics. Thus, we will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.</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/NCT03234530
org study id: GCO 16-0899
secondary id: U01OH011326-01A1
nct id: NCT03234530
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study focuses on the prevalence and identification of kidney disease among participants
      of the WTC Health Program and the study team are planning to assess kidney disease in a
      multi-factorial manner. The first aim of this study is to correlate kidney dysfunction with
      9/11 exposure, and the study team predicts that exposure to 9/11 is an independent risk
      factor in kidney disease among the WTC Health Program participants. Secondly, the study team
      proposes that a well-established WTC-related condition, obstructive sleep apnea (OSA), is
      independently associated with kidney disease. In addition, the study team believe there is a
      temporal causative relationship between evidence of kidney disease and the severity of OSA.
      Finally, the last aim is to further identify and explore potential mechanisms and phenotypes
      of kidney disease in participants of the WTC Health Programs.

      Regardless of whether the analyses support or reject these hypotheses, the findings will be
      of equally great public health importance. Successful completion of the proposed research
      would address a critical knowledge gap regarding the risk of kidney damage among this group
      of patients, and would inform future mechanistic studies with the potential to impact
      prevention.
Exposure to environmental toxins results in significant long-term health effects in workers.
      More than 91,000 rescue and recovery workers and volunteers at the World Trade Center (WTC)
      sustained exposure to thousands of tons of coarse and fine particulate matter. Thousands of
      responders are currently treated for WTC-related health conditions or may be at risk for
      worsening health. Toxic effects of particulate matter are known to affect the pulmonary,
      renal and cardiovascular systems. The specific effects of the exposure to 9/11 are partly
      known, and require further investigation, as outlined in the Zadroga Act (Public Law111-347).

      This study builds on the preliminary data to address a critical knowledge gap about the risk
      of kidney damage among WTC responders, the progression of kidney decline since exposure, and
      the association of kidney disease with a defined WTC-related diagnosis, obstructive sleep
      apnea (OSA). Successful completion of the proposed research would address a critical
      knowledge gap regarding the risk of kidney damage and the relationship to important chronic
      diseases (OSA and immune-mediated disease) among WTC participants, and would inform future
      mechanistic studies with the potential to impact disease prevention.

      Specific Aim 1: To quantify the risk of kidney damage and the relationship to 9/11 exposure
      among WTC Health Program participants. Currently, the cohort of 406 first responders
      represents the sole dedicated evaluation of kidney disease in WTC Health Program
      participants. The study team will test the hypothesis that exposure to 9/11 is independently
      associated with kidney disease and enrich the enrollment of the current study population with
      a diversified population including categories of workers who have not been enrolled, as well
      as a control group of urban workers (NYC) not exposed to the dust from the WTC.

      Aim 1a. The study team hypothesize that albuminuria and decreased estimated glomerular
      filtration rate (eGFR) will occur more frequently in WTC responders than in the general
      population and will correlate with the degree of exposure as defined by the previously
      defined WTC exposure score (adjusting for demographics, family history of chronic kidney
      disease (CKD), and diagnosed, treated or laboratory confirmed diabetes and hypertension). The
      study team will also assess established urine biomarkers of proximal tubular injury,
      including β2-M, Kidney Injury Molecule-1 (KIM-1), and Interleukin 18 (IL-18), as well as
      markers of distal tubular function, Loop of Henle function, and tubulointerstitial
      inflammation.

      Aim 1b. The study team hypothesize that initial exposure to 9/11 contributed to reduction in
      renal function over time. The study team will quantify change in renal function over time by
      analyzing eGFR at WTC Health Program Visit 1 (V1) and subsequent visits, adjusting for known
      co-morbid conditions.

      Aim 1c. The study team will create a repository of WTC responders with established kidney
      disease (including relatively rare disease) to qualitatively evaluate and describe the
      spectrum of kidney disease in the entire WTC population and compare to patterns of kidney
      disease in the general population. The study team will actively enlist those with a verified
      physician diagnosis of kidney disease, and collect biopsy reports and slides for review.

      Specific Aim 2: Evaluate the association of kidney disease and the established WTC-related
      condition, OSA.

      Aim 2a. OSA is particularly prevalent among WTC cohorts. The study team hypothesize that
      there is an independent association between prevalent OSA and prevalent kidney disease.

      Aim2b. The study team hypothesize that OSA independently contributes to the progression of
      kidney disease. The study team will assess the temporal relationship of eGFR decline to the
      presence and severity of OSA, using longitudinal data from the WTC data center.

      Specific Aim 3: To evaluate potential mechanisms of kidney injury in WTC Health Program
      participants.

      Aim3a. In order to understand the role of chronic inflammation, the study team will evaluate
      established inflammatory markers which have been implicated as potential mediators of both
      OSA and CKD, including IL-10, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, IL-12p70.,
      high sensitivity C-reactive protein (hs-CRP), and white blood cell count (WBC).

      Aim3b. Based on the preliminary data noting increases in heavy metal levels in urine and
      blood, the study team will narrow the focus to evaluate the role of cadmium and lead in the
      development of kidney disease with evaluations of lead content in bone (marker of long-term
      exposure) as well as in blood. Since study participants include law enforcement personnel
      (with known exposure to lead), the characterization of bone lead levels will have an
      important health impact, whether or not a relationship to 9/11 is detected.

      Aim3c. In a registry cohort of WTC responders with established kidney disease the study team
      will explore potential mechanisms as determined by the observed patterns of disease by
      developing a comprehensive repository of data on WTC Health Program participants with common
      and rare kidney diseases, the study team will define specific clinical profiles and identify
      potential mechanisms that warrant future study. Importantly, the study team will develop a
      process across all WTC Health Programs (inclusive of approximately 50,000 individuals), to
      monitor those with early kidney disease as well as those with biopsy-proven kidney disease,
      at any stage.
observational model: Case-Control
time perspective: Cross-Sectional
measure: glomerular filtration rate (eGFR)
time frame: day 1
description: eGFR will be calculated using the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equations. The proposed studies will evaluate differences in the combined creatinine-cystatin C eGFR, which provides the most accurate estimate of GFR, and the creatinine-based CKD-EPI eGFR, which is more practical for use in clinical practice and in monitoring programs. Values > 200 will be set to 200mL/min/1.73m2
measure: albuminuria
time frame: day 1
description: albumin level in urine
measure: Berlin questionnaire
time frame: day 1
description: Those who are not diagnosed with sleep apnea will be assessed for risk of developing sleep apnea using the Berlin questionnaire. It includes 11 questions organized into three categories, 5 questions related to snoring and the cessation of breathing in category 1, 4 questions related to daytime sleepiness in category 2, 1 question about high blood pressure, and 1 question regarding BMI in category 3. When two of three categories are classified as positive for a patient, the patient is rated as being at high risk of having OSA.
measure: apnea-hypopnea index (AHI)
time frame: day 1
description: Those at high risk for sleep apnea will undergo home sleep a study test to determine apnea hypopnea index (AHI).
Those diagnosed with sleep apnea, latest sleep study will be used to obtain AHI. To determine AHI, add the total number of apnea events, plus hypopnea events and divide by the total number of minutes of actual sleep time, then multiply by 60. AHI - Apnea Hypopnea Index - The # of apneas and hypopneas per hour.
arm group label: WTC responders
description: WTC Health Program participants
arm group label: Urban workers
description: Control group of urban workers in NYC not exposed to the dust from the WTC
Serum, plasma, urine
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mary Ann McLaughlin, MD, MPH
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Maryann Mclaughlin
investigator title: Associate Professor
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
sharing ipd: Yes
ipd description: The final research data will be a computerized dataset and includes self-reported demographic and medical data, responses from standard questionnaires, as well as results of laboratory tests (urine and blood samples) . Even though the final dataset will be stripped of identifiers prior to release for sharing, we believe that there remains the possibility of deductive disclosure of subjects with unusual characteristics. Thus, we will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.