<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/NCT03292900</url>
  </required_header>
  <id_info>
    <org_study_id>Geneticure600</org_study_id>
    <nct_id>NCT03292900</nct_id>
  </id_info>
  <brief_title>Association Between Genetic Algorithm to Predict Hypertension Therapy and Response to Treatment</brief_title>
  <official_title>Association Between a Pharmacogenetic Algorithm to Predict Blood Pressure Therapy With Blood Pressure Response to Anti-Hypertensive Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Geneticure, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fairview Health Services</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Geneticure, LLC</source>
  <oversight_info>
    <has_dmc>No</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>
      To assess the effectiveness of the use of a patient's genes to predict which hypertension&#xD;
      therapy is successful&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypertension is known to have a strong heritable component. Previous work has demonstrated&#xD;
      that sons of hypertensive patients are more likely to be hypertensive when compared to sons&#xD;
      of normotensive individuals. Additionally, monozygotic twins are more likely to share&#xD;
      hypertension than dizygotic twins who are more likely than non-twin siblings to share&#xD;
      hypertension. Each of these previous studies demonstrate that genetics plays a role in the&#xD;
      development of hypertension. For each major class of drugs (diuretic, vasodilator, and&#xD;
      β-blocker) the effectiveness rate ranges from 40-60%. Contrary to common belief, even a small&#xD;
      ~10-20% of patients have an increase in blood pressure with a given anti-hypertensive&#xD;
      medication. These effectiveness rates go far beyond adherence in that these previous trials&#xD;
      have controlled for medication adherence. In addition to this controlled studies,&#xD;
      epidemiologic data has demonstrated that 40% of patients who take their medication, as&#xD;
      prescribed by their clinician, do not have their blood pressure under control.&#xD;
&#xD;
      Unfortunately, despite a significant impulse in the medical community to move towards an&#xD;
      &quot;individualized medicine&quot; approach to patient centered treatment, the current clinical&#xD;
      treatment strategy is based on a set algorithm which does not take into account individual&#xD;
      patient differences. Rather, physicians are guided to choose a drug (one out of many options)&#xD;
      in a given class of drugs and use that specific drug as a &quot;first line therapy&quot; (typically&#xD;
      initiating with the diuretic class) and titrate that specific drug of choice to therapeutic&#xD;
      dosage regardless of efficacy2. It is only after a prolonged course of treatment with that&#xD;
      specific class of drug that clinical efficacy is determined (typically three months). At this&#xD;
      stage, if clinical guideline goals for blood pressure have not been met, it is often&#xD;
      recommended that the patient remain on the &quot;first line therapy&quot; whilst an additional drug&#xD;
      from a different class of drugs (typically an Angiotensin converting enzyme inhibitor (ACE&#xD;
      inhibitor) or Angiotensin II receptor blocker (ARB)) is added to the pharmacologic regimen.&#xD;
      Again, this drug is titrated to recommended therapeutic dosage and another prolonged course&#xD;
      of treatment is initiated before clinical efficacy is determined (an additional three months&#xD;
      - six months since initiation of treatment). If at this point, clinical guideline goals for&#xD;
      blood pressure have not been met, a third drug from a third class of drugs (typically a&#xD;
      beta-blocker) is added and the process is repeated (another three months - nine months from&#xD;
      initiation of treatment). Further, if clinical guideline goals have continued to be elusive,&#xD;
      the diagnosis of refractory hypertension is added and the process is reinitiated with a&#xD;
      different combination of drugs, different classes of drugs, different drug options within a&#xD;
      given class of drugs, different dosages, or all of the above. Thus, from the time of initial&#xD;
      diagnosis and the start of treatment to the point in which blood pressure is adequately&#xD;
      controlled may take anywhere from three months to well over one year. This trial-and-error&#xD;
      standard of care is clearly not optimal.&#xD;
&#xD;
      The blood pressure panel created by Geneticure has been created to comprehensively assess&#xD;
      seventeen common genetic variants in the liver (drug metabolizing enzyme) cardiac, vascular,&#xD;
      and renal systems that can improve therapeutic guidance for the clinician based on known&#xD;
      functional alterations of the protein through these genetic changes, as well as demonstrated&#xD;
      effects of certain drug classes on these various genotypes. Based on this information, a&#xD;
      clinician can guide therapy with knowledge specific to their patient, rather than&#xD;
      &quot;trial-and-error&quot; based on population data and using drugs with least side effects initially.&#xD;
&#xD;
      To assess the effectiveness of the use of a patient's genes to predict which hypertension&#xD;
      therapy is successful, as measured by:&#xD;
&#xD;
        1. Level of blood pressure control (&lt;140/&lt;90)&#xD;
&#xD;
        2. Change in blood pressure from baseline to control&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Actual">January 15, 2019</completion_date>
  <primary_completion_date type="Actual">December 15, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Level of Blood Pressure Control</measure>
    <time_frame>5 years</time_frame>
    <description>how many participants are &lt;140/&lt;90 with genetic prediction</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of medications needed to obtain blood pressure control</measure>
    <time_frame>5 years</time_frame>
    <description>Do those whose genes match therapy need fewer medications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to blood pressure control</measure>
    <time_frame>5 years</time_frame>
    <description>If control faster if associated with genes that predict control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of office visits to obtain blood pressure control</measure>
    <time_frame>5 years</time_frame>
    <description>Are office visits fewer if genes would have been used to predict control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>side effects from hypertension therapy</measure>
    <time_frame>5 years</time_frame>
    <description>Do patients have more side effects on therapies that do not align with their predictive genes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypertension associated adverse events during the course of treatment</measure>
    <time_frame>5 years</time_frame>
    <description>Do patients have more side adverse events on therapies that do not align with their predictive genes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in BP from treatment to control</measure>
    <time_frame>5 years</time_frame>
    <description>Modeled by BP genes</description>
  </secondary_outcome>
  <enrollment type="Actual">758</enrollment>
  <condition>Hypertension</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Hypertensive patients who have achieved blood pressure control&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is able and willing to provide informed consent&#xD;
&#xD;
          2. Subject is ≥ 20 and ≤ 85 years of age&#xD;
&#xD;
          3. Subject with diagnosis of Hypertension for a minimum of 1 year&#xD;
&#xD;
          4. Subject has been on the same class/classes of blood pressure medication for a minimum&#xD;
             of 6 months. Note: A change in dosage, frequency, or specific medication is acceptable&#xD;
             as long as there have been no changes to the class/classes of medications prescribed.&#xD;
&#xD;
          5. Subject with a Body Mass Index (BMI) ≥ 19 and ≤ 45&#xD;
&#xD;
          6. Subject is currently prescribed and taking one of the following classes of medications&#xD;
             alone or in combination with each other.&#xD;
&#xD;
               -  Diuretics (thiazide or thiazide-like)&#xD;
&#xD;
               -  ACE Inhibitors&#xD;
&#xD;
               -  Angiotensin Receptor Blocker (ARB)&#xD;
&#xD;
               -  Beta-blockers&#xD;
&#xD;
               -  Ca+ Channel Blockers&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has a diagnosis of secondary hypertension or is experiencing a complication of&#xD;
             pregnancy.&#xD;
&#xD;
          2. Subject is currently prescribed and taking any additional class of medication(s) for&#xD;
             high blood pressure not included in the list above&#xD;
&#xD;
          3. Subject has Systolic BP &gt; 190 or Diastolic BP &gt; 120 documented within the six months&#xD;
             prior to visit.&#xD;
&#xD;
          4. Any other reason that the subject is inappropriate for study enrollment in the opinion&#xD;
             of the Investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pamela Phelps, PharmD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fairview Health System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fairview Clinic - New Brighton</name>
      <address>
        <city>New Brighton</city>
        <state>Minnesota</state>
        <zip>55112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>February 12, 2019</last_update_submitted>
  <last_update_submitted_qc>February 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 22, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT03292900/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03292900
org study id: Geneticure600
nct id: NCT03292900
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To assess the effectiveness of the use of a patient's genes to predict which hypertension
      therapy is successful
Hypertension is known to have a strong heritable component. Previous work has demonstrated
      that sons of hypertensive patients are more likely to be hypertensive when compared to sons
      of normotensive individuals. Additionally, monozygotic twins are more likely to share
      hypertension than dizygotic twins who are more likely than non-twin siblings to share
      hypertension. Each of these previous studies demonstrate that genetics plays a role in the
      development of hypertension. For each major class of drugs (diuretic, vasodilator, and
      β-blocker) the effectiveness rate ranges from 40-60%. Contrary to common belief, even a small
      ~10-20% of patients have an increase in blood pressure with a given anti-hypertensive
      medication. These effectiveness rates go far beyond adherence in that these previous trials
      have controlled for medication adherence. In addition to this controlled studies,
      epidemiologic data has demonstrated that 40% of patients who take their medication, as
      prescribed by their clinician, do not have their blood pressure under control.

      Unfortunately, despite a significant impulse in the medical community to move towards an
      "individualized medicine" approach to patient centered treatment, the current clinical
      treatment strategy is based on a set algorithm which does not take into account individual
      patient differences. Rather, physicians are guided to choose a drug (one out of many options)
      in a given class of drugs and use that specific drug as a "first line therapy" (typically
      initiating with the diuretic class) and titrate that specific drug of choice to therapeutic
      dosage regardless of efficacy2. It is only after a prolonged course of treatment with that
      specific class of drug that clinical efficacy is determined (typically three months). At this
      stage, if clinical guideline goals for blood pressure have not been met, it is often
      recommended that the patient remain on the "first line therapy" whilst an additional drug
      from a different class of drugs (typically an Angiotensin converting enzyme inhibitor (ACE
      inhibitor) or Angiotensin II receptor blocker (ARB)) is added to the pharmacologic regimen.
      Again, this drug is titrated to recommended therapeutic dosage and another prolonged course
      of treatment is initiated before clinical efficacy is determined (an additional three months
      - six months since initiation of treatment). If at this point, clinical guideline goals for
      blood pressure have not been met, a third drug from a third class of drugs (typically a
      beta-blocker) is added and the process is repeated (another three months - nine months from
      initiation of treatment). Further, if clinical guideline goals have continued to be elusive,
      the diagnosis of refractory hypertension is added and the process is reinitiated with a
      different combination of drugs, different classes of drugs, different drug options within a
      given class of drugs, different dosages, or all of the above. Thus, from the time of initial
      diagnosis and the start of treatment to the point in which blood pressure is adequately
      controlled may take anywhere from three months to well over one year. This trial-and-error
      standard of care is clearly not optimal.

      The blood pressure panel created by Geneticure has been created to comprehensively assess
      seventeen common genetic variants in the liver (drug metabolizing enzyme) cardiac, vascular,
      and renal systems that can improve therapeutic guidance for the clinician based on known
      functional alterations of the protein through these genetic changes, as well as demonstrated
      effects of certain drug classes on these various genotypes. Based on this information, a
      clinician can guide therapy with knowledge specific to their patient, rather than
      "trial-and-error" based on population data and using drugs with least side effects initially.

      To assess the effectiveness of the use of a patient's genes to predict which hypertension
      therapy is successful, as measured by:

        1. Level of blood pressure control (<140/<90)

        2. Change in blood pressure from baseline to control
observational model: Cohort
time perspective: Retrospective
measure: Level of Blood Pressure Control
time frame: 5 years
description: how many participants are <140/<90 with genetic prediction
measure: Number of medications needed to obtain blood pressure control
time frame: 5 years
description: Do those whose genes match therapy need fewer medications
measure: Time to blood pressure control
time frame: 5 years
description: If control faster if associated with genes that predict control
measure: Number of office visits to obtain blood pressure control
time frame: 5 years
description: Are office visits fewer if genes would have been used to predict control
measure: side effects from hypertension therapy
time frame: 5 years
description: Do patients have more side effects on therapies that do not align with their predictive genes
measure: Hypertension associated adverse events during the course of treatment
time frame: 5 years
description: Do patients have more side adverse events on therapies that do not align with their predictive genes
measure: Change in BP from treatment to control
time frame: 5 years
description: Modeled by BP genes
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: No
last name: Pamela Phelps, PharmD
role: Principal Investigator
affiliation: Fairview Health System
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hypertension
sharing ipd: No
provided document: 