<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/NCT01719367</url>
  </required_header>
  <id_info>
    <org_study_id>130298</org_study_id>
    <nct_id>NCT01719367</nct_id>
  </id_info>
  <brief_title>Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation</brief_title>
  <official_title>Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Atrial fibrillation (AF), the most common sustained heart rhythm disorder, is becoming&#xD;
      increasingly prevalent in the Western world. The number of people with AF in the United&#xD;
      States is projected to roughly double by the year 2050, to an estimated 6-12 million. For&#xD;
      many patients with AF, rate control with atrioventricular (AV) node blockers is a widely&#xD;
      accepted therapeutic strategy. These agents control heart rate, thus preventing symptoms and&#xD;
      systolic heart failure associated with tachycardia due to a rapid ventricular response to AF.&#xD;
      Beta-blockers are widely accepted as first line agents for rate control in AF, especially&#xD;
      when patients have concomitant hypertension (HTN), coronary artery disease, cardiomyopathies,&#xD;
      or heart failure (HF). As a class, beta-blockers are among the most commonly prescribed&#xD;
      cardiovascular medications.&#xD;
&#xD;
      Among patients with AF treated with beta-blockers, the heart rate (HR) response varies&#xD;
      substantially. Sometimes, adequate rate control can be achieved by titration of the&#xD;
      beta-blocker dose; but frequently, additional AV nodal blockers and/or digoxin are necessary.&#xD;
      In some cases, adequate rate control cannot be achieved even with the simultaneous use of&#xD;
      multiple AV nodal blockers, necessitating mechanical ablation of the AV node and permanent&#xD;
      pacemaker implantation.&#xD;
&#xD;
      Patient-specific variables that influence the response to beta-blockers include comorbid&#xD;
      conditions, weight, age, and level of physical activity. Ethnic differences in the response&#xD;
      to beta-blockers for the treatment of HTN and HF are well-described. However, the&#xD;
      contribution of genetic variants to beta-blocker efficacy in AF is unknown. We propose to&#xD;
      study whether the ADRB1 Gly389Asp SNP reduces response to beta-blockade in subjects with&#xD;
      permanent AF.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Pre- and Post-atenolol Ventricular Rate Response After 5 Minutes of Exercise</measure>
    <time_frame>after 5minutes of exercise</time_frame>
    <description>After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise</measure>
    <time_frame>after 10 amd 15 minutes of exercise</time_frame>
    <description>After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Atenolol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atenolol</intervention_name>
    <arm_group_label>Atenolol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must be at least 18 years of age.&#xD;
&#xD;
          -  Subjects must have a history of persistent AF currently treated with a rate control&#xD;
             strategy.&#xD;
&#xD;
          -  Subjects should be willing to give written, informed consent.&#xD;
&#xD;
          -  Subjects must be willing and able to participate in the exercise protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  New York Heart Association Class III or IV heart failure.&#xD;
&#xD;
          -  A history of heart failure induced by tachy-arrhythmia.&#xD;
&#xD;
          -  A history of coronary artery disease and the presence of at least one of the&#xD;
             following:&#xD;
&#xD;
               -  Canadian Class III or IV angina.&#xD;
&#xD;
               -  Recent myocardial infarction, coronary artery bypass grafting, or percutaneous&#xD;
                  coronary intervention within 6 months.&#xD;
&#xD;
          -  Severe renal or hepatic impairment.&#xD;
&#xD;
          -  Subjects who have a clinically significant allergy/intolerance to atenolol, including&#xD;
             a history of beta-blocker induced bronchospasm.&#xD;
&#xD;
          -  Females who are pregnant or nursing.&#xD;
&#xD;
          -  History of severe AV node dysfunction/pacemaker dependence.&#xD;
&#xD;
          -  Subjects who have a systolic blood pressure &lt; 90 mm Hg or resting Ventricular Rate &lt;50&#xD;
             or &gt;120 per minute on the day of the study.&#xD;
&#xD;
          -  Patients currently taking Vaughan-Williams Class I or III anti-arrhythmic drugs.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>European Heart Rhythm Association; Heart Rhythm Society; Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Hunt SA, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Zamorano JL; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006 Aug 15;48(4):854-906. doi: 10.1016/j.jacc.2006.07.009. No abstract available. Erratum In: J Am Coll Cardiol. 2007 Aug 7;50(6):562.</citation>
    <PMID>16904574</PMID>
  </reference>
  <reference>
    <citation>Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001 May 9;285(18):2370-5. doi: 10.1001/jama.285.18.2370.</citation>
    <PMID>11343485</PMID>
  </reference>
  <reference>
    <citation>Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, Seward JB, Tsang TS. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation. 2006 Jul 11;114(2):119-25. doi: 10.1161/CIRCULATIONAHA.105.595140. Epub 2006 Jul 3. Erratum In: Circulation. 2006 Sep 12;114(11):e498.</citation>
    <PMID>16818816</PMID>
  </reference>
  <reference>
    <citation>Beta-Blocker Evaluation of Survival Trial Investigators; Eichhorn EJ, Domanski MJ, Krause-Steinrauf H, Bristow MR, Lavori PW. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med. 2001 May 31;344(22):1659-67. doi: 10.1056/NEJM200105313442202.</citation>
    <PMID>11386264</PMID>
  </reference>
  <reference>
    <citation>Havlik RJ, Garrison RJ, Fabsitz R, Feinleib M. Variability of heart rate, P-R, QRS and Q-T durations in twins. J Electrocardiol. 1980;13(1):45-8. doi: 10.1016/s0022-0736(80)80008-2.</citation>
    <PMID>7188949</PMID>
  </reference>
  <reference>
    <citation>Hanson B, Tuna N, Bouchard T, Heston L, Eckert E, Lykken D, Segal N, Rich S. Genetic factors in the electrocardiogram and heart rate of twins reared apart and together. Am J Cardiol. 1989 Mar 1;63(9):606-9. doi: 10.1016/0002-9149(89)90907-7.</citation>
    <PMID>2919564</PMID>
  </reference>
  <reference>
    <citation>Levin MC, Marullo S, Muntaner O, Andersson B, Magnusson Y. The myocardium-protective Gly-49 variant of the beta 1-adrenergic receptor exhibits constitutive activity and increased desensitization and down-regulation. J Biol Chem. 2002 Aug 23;277(34):30429-35. doi: 10.1074/jbc.M200681200. Epub 2002 May 28.</citation>
    <PMID>12034720</PMID>
  </reference>
  <reference>
    <citation>Mason DA, Moore JD, Green SA, Liggett SB. A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem. 1999 Apr 30;274(18):12670-4. doi: 10.1074/jbc.274.18.12670.</citation>
    <PMID>10212248</PMID>
  </reference>
  <reference>
    <citation>Sandilands A, Yeo G, Brown MJ, O'Shaughnessy KM. Functional responses of human beta1 adrenoceptors with defined haplotypes for the common 389R&gt;G and 49S&gt;G polymorphisms. Pharmacogenetics. 2004 Jun;14(6):343-9. doi: 10.1097/00008571-200406000-00003.</citation>
    <PMID>15247626</PMID>
  </reference>
  <reference>
    <citation>Mialet Perez J, Rathz DA, Petrashevskaya NN, Hahn HS, Wagoner LE, Schwartz A, Dorn GW, Liggett SB. Beta 1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure. Nat Med. 2003 Oct;9(10):1300-5. doi: 10.1038/nm930. Epub 2003 Sep 14.</citation>
    <PMID>14502278</PMID>
  </reference>
  <reference>
    <citation>Liu J, Liu ZQ, Yu BN, Xu FH, Mo W, Zhou G, Liu YZ, Li Q, Zhou HH. beta1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension. Clin Pharmacol Ther. 2006 Jul;80(1):23-32. doi: 10.1016/j.clpt.2006.03.004. Epub 2006 Jun 8.</citation>
    <PMID>16815314</PMID>
  </reference>
  <reference>
    <citation>Johnson JA, Zineh I, Puckett BJ, McGorray SP, Yarandi HN, Pauly DF. Beta 1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clin Pharmacol Ther. 2003 Jul;74(1):44-52. doi: 10.1016/S0009-9236(03)00068-7.</citation>
    <PMID>12844134</PMID>
  </reference>
  <reference>
    <citation>Small KM, Forbes SL, Rahman FF, Bridges KM, Liggett SB. A four amino acid deletion polymorphism in the third intracellular loop of the human alpha 2C-adrenergic receptor confers impaired coupling to multiple effectors. J Biol Chem. 2000 Jul 28;275(30):23059-64. doi: 10.1074/jbc.M000796200.</citation>
    <PMID>10801795</PMID>
  </reference>
  <reference>
    <citation>Lobmeyer MT, Gong Y, Terra SG, Beitelshees AL, Langaee TY, Pauly DF, Schofield RS, Hamilton KK, Herbert Patterson J, Adams KF Jr, Hill JA, Aranda JM Jr, Johnson JA. Synergistic polymorphisms of beta1 and alpha2C-adrenergic receptors and the influence on left ventricular ejection fraction response to beta-blocker therapy in heart failure. Pharmacogenet Genomics. 2007 Apr;17(4):277-82. doi: 10.1097/FPC.0b013e3280105245.</citation>
    <PMID>17496726</PMID>
  </reference>
  <reference>
    <citation>Kaab S, Darbar D, van Noord C, Dupuis J, Pfeufer A, Newton-Cheh C, Schnabel R, Makino S, Sinner MF, Kannankeril PJ, Beckmann BM, Choudry S, Donahue BS, Heeringa J, Perz S, Lunetta KL, Larson MG, Levy D, MacRae CA, Ruskin JN, Wacker A, Schomig A, Wichmann HE, Steinbeck G, Meitinger T, Uitterlinden AG, Witteman JC, Roden DM, Benjamin EJ, Ellinor PT. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. Eur Heart J. 2009 Apr;30(7):813-9. doi: 10.1093/eurheartj/ehn578. Epub 2009 Jan 13.</citation>
    <PMID>19141561</PMID>
  </reference>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>October 29, 2012</study_first_submitted>
  <study_first_submitted_qc>October 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 1, 2012</study_first_posted>
  <results_first_submitted>May 22, 2019</results_first_submitted>
  <results_first_submitted_qc>June 14, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 17, 2019</results_first_posted>
  <last_update_submitted>June 14, 2019</last_update_submitted>
  <last_update_submitted_qc>June 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Baseline (pre-atenolol)</keyword>
  <keyword>Post-atenolol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atenolol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Atenolol: Ancestral Alleles</title>
          <description>Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.&#xD;
participants have Ancestral Alleles</description>
        </group>
        <group group_id="P2">
          <title>Atenolol: Variant Carriers</title>
          <description>Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.&#xD;
participants have Variant Carriers</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The PI of this study left Vanderbilt. Limited data are available for this study. Baseline data are not available per-arm, therefore, only the baseline data for overall population is being reported.</population>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>all participants</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="38"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.5" lower_limit="60" upper_limit="74.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Pre- and Post-atenolol Ventricular Rate Response After 5 Minutes of Exercise</title>
        <description>After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.</description>
        <time_frame>after 5minutes of exercise</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Atenolol: Ancestral Alleles</title>
            <description>Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.&#xD;
These patients have Ancestral Alleles</description>
          </group>
          <group group_id="O2">
            <title>Atenolol: Variant Carriers</title>
            <description>Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.&#xD;
These patients have Variant Carriers</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pre- and Post-atenolol Ventricular Rate Response After 5 Minutes of Exercise</title>
          <description>After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.</description>
          <units>beats per minute</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10" lower_limit="-18.6" upper_limit="-1.4"/>
                    <measurement group_id="O2" value="-13" lower_limit="-20.2" upper_limit="-5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise</title>
        <description>After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.</description>
        <time_frame>after 10 amd 15 minutes of exercise</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Atenolol: Ancestral Alleles</title>
            <description>Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.&#xD;
These patients have Ancestral Alleles</description>
          </group>
          <group group_id="O2">
            <title>Atenolol: Variant Carriers</title>
            <description>Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.&#xD;
These patients have Variant Carriers</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise</title>
          <description>After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.</description>
          <units>beats per minute</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After 10 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11" lower_limit="-21.9" upper_limit="-0.1"/>
                    <measurement group_id="O2" value="-19.7" lower_limit="-25.6" upper_limit="-13.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After 15 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-25.5" lower_limit="-67" upper_limit="-16.8"/>
                    <measurement group_id="O2" value="-35.2" lower_limit="-53.3" upper_limit="-17.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>during study visit, 1 day</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Atenolol: Ancestral Alleles</title>
          <description>Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.&#xD;
These patients have Ancestral Alleles</description>
        </group>
        <group group_id="E2">
          <title>Atenolol: Variant Carriers</title>
          <description>Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.&#xD;
These patients have Variant Carriers</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Matthew Kolek, MD</name_or_title>
      <organization>Florida Electrophysiology Associates</organization>
      <phone>(561) 434-0353</phone>
      <email>info@heartrhythmexperts.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01719367
org study id: 130298
nct id: NCT01719367
lead sponsor: 
has dmc: No
Atrial fibrillation (AF), the most common sustained heart rhythm disorder, is becoming
      increasingly prevalent in the Western world. The number of people with AF in the United
      States is projected to roughly double by the year 2050, to an estimated 6-12 million. For
      many patients with AF, rate control with atrioventricular (AV) node blockers is a widely
      accepted therapeutic strategy. These agents control heart rate, thus preventing symptoms and
      systolic heart failure associated with tachycardia due to a rapid ventricular response to AF.
      Beta-blockers are widely accepted as first line agents for rate control in AF, especially
      when patients have concomitant hypertension (HTN), coronary artery disease, cardiomyopathies,
      or heart failure (HF). As a class, beta-blockers are among the most commonly prescribed
      cardiovascular medications.

      Among patients with AF treated with beta-blockers, the heart rate (HR) response varies
      substantially. Sometimes, adequate rate control can be achieved by titration of the
      beta-blocker dose; but frequently, additional AV nodal blockers and/or digoxin are necessary.
      In some cases, adequate rate control cannot be achieved even with the simultaneous use of
      multiple AV nodal blockers, necessitating mechanical ablation of the AV node and permanent
      pacemaker implantation.

      Patient-specific variables that influence the response to beta-blockers include comorbid
      conditions, weight, age, and level of physical activity. Ethnic differences in the response
      to beta-blockers for the treatment of HTN and HF are well-described. However, the
      contribution of genetic variants to beta-blocker efficacy in AF is unknown. We propose to
      study whether the ADRB1 Gly389Asp SNP reduces response to beta-blockade in subjects with
      permanent AF.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Pre- and Post-atenolol Ventricular Rate Response After 5 Minutes of Exercise
time frame: after 5minutes of exercise
description: After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.
measure: Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise
time frame: after 10 amd 15 minutes of exercise
description: After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.
arm group label: Atenolol
arm group type: Experimental
description: Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.
intervention type: Drug
intervention name: Atenolol
arm group label: Atenolol
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
citation: European Heart Rhythm Association; Heart Rhythm Society; Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Hunt SA, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Zamorano JL; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006 Aug 15;48(4):854-906. doi: 10.1016/j.jacc.2006.07.009. No abstract available. Erratum In: J Am Coll Cardiol. 2007 Aug 7;50(6):562.
PMID: 16904574
citation: Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001 May 9;285(18):2370-5. doi: 10.1001/jama.285.18.2370.
PMID: 11343485
citation: Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, Seward JB, Tsang TS. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation. 2006 Jul 11;114(2):119-25. doi: 10.1161/CIRCULATIONAHA.105.595140. Epub 2006 Jul 3. Erratum In: Circulation. 2006 Sep 12;114(11):e498.
PMID: 16818816
citation: Beta-Blocker Evaluation of Survival Trial Investigators; Eichhorn EJ, Domanski MJ, Krause-Steinrauf H, Bristow MR, Lavori PW. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med. 2001 May 31;344(22):1659-67. doi: 10.1056/NEJM200105313442202.
PMID: 11386264
citation: Havlik RJ, Garrison RJ, Fabsitz R, Feinleib M. Variability of heart rate, P-R, QRS and Q-T durations in twins. J Electrocardiol. 1980;13(1):45-8. doi: 10.1016/s0022-0736(80)80008-2.
PMID: 7188949
citation: Hanson B, Tuna N, Bouchard T, Heston L, Eckert E, Lykken D, Segal N, Rich S. Genetic factors in the electrocardiogram and heart rate of twins reared apart and together. Am J Cardiol. 1989 Mar 1;63(9):606-9. doi: 10.1016/0002-9149(89)90907-7.
PMID: 2919564
citation: Levin MC, Marullo S, Muntaner O, Andersson B, Magnusson Y. The myocardium-protective Gly-49 variant of the beta 1-adrenergic receptor exhibits constitutive activity and increased desensitization and down-regulation. J Biol Chem. 2002 Aug 23;277(34):30429-35. doi: 10.1074/jbc.M200681200. Epub 2002 May 28.
PMID: 12034720
citation: Mason DA, Moore JD, Green SA, Liggett SB. A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem. 1999 Apr 30;274(18):12670-4. doi: 10.1074/jbc.274.18.12670.
PMID: 10212248
citation: Sandilands A, Yeo G, Brown MJ, O'Shaughnessy KM. Functional responses of human beta1 adrenoceptors with defined haplotypes for the common 389R>G and 49S>G polymorphisms. Pharmacogenetics. 2004 Jun;14(6):343-9. doi: 10.1097/00008571-200406000-00003.
PMID: 15247626
citation: Mialet Perez J, Rathz DA, Petrashevskaya NN, Hahn HS, Wagoner LE, Schwartz A, Dorn GW, Liggett SB. Beta 1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure. Nat Med. 2003 Oct;9(10):1300-5. doi: 10.1038/nm930. Epub 2003 Sep 14.
PMID: 14502278
citation: Liu J, Liu ZQ, Yu BN, Xu FH, Mo W, Zhou G, Liu YZ, Li Q, Zhou HH. beta1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension. Clin Pharmacol Ther. 2006 Jul;80(1):23-32. doi: 10.1016/j.clpt.2006.03.004. Epub 2006 Jun 8.
PMID: 16815314
citation: Johnson JA, Zineh I, Puckett BJ, McGorray SP, Yarandi HN, Pauly DF. Beta 1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clin Pharmacol Ther. 2003 Jul;74(1):44-52. doi: 10.1016/S0009-9236(03)00068-7.
PMID: 12844134
citation: Small KM, Forbes SL, Rahman FF, Bridges KM, Liggett SB. A four amino acid deletion polymorphism in the third intracellular loop of the human alpha 2C-adrenergic receptor confers impaired coupling to multiple effectors. J Biol Chem. 2000 Jul 28;275(30):23059-64. doi: 10.1074/jbc.M000796200.
PMID: 10801795
citation: Lobmeyer MT, Gong Y, Terra SG, Beitelshees AL, Langaee TY, Pauly DF, Schofield RS, Hamilton KK, Herbert Patterson J, Adams KF Jr, Hill JA, Aranda JM Jr, Johnson JA. Synergistic polymorphisms of beta1 and alpha2C-adrenergic receptors and the influence on left ventricular ejection fraction response to beta-blocker therapy in heart failure. Pharmacogenet Genomics. 2007 Apr;17(4):277-82. doi: 10.1097/FPC.0b013e3280105245.
PMID: 17496726
citation: Kaab S, Darbar D, van Noord C, Dupuis J, Pfeufer A, Newton-Cheh C, Schnabel R, Makino S, Sinner MF, Kannankeril PJ, Beckmann BM, Choudry S, Donahue BS, Heeringa J, Perz S, Lunetta KL, Larson MG, Levy D, MacRae CA, Ruskin JN, Wacker A, Schomig A, Wichmann HE, Steinbeck G, Meitinger T, Uitterlinden AG, Witteman JC, Roden DM, Benjamin EJ, Ellinor PT. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. Eur Heart J. 2009 Apr;30(7):813-9. doi: 10.1093/eurheartj/ehn578. Epub 2009 Jan 13.
PMID: 19141561
responsible party type: Sponsor
mesh term: Atrial Fibrillation
mesh term: Atenolol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 