<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/NCT04422756</url>
  </required_header>
  <id_info>
    <org_study_id>REB16-2322</org_study_id>
    <nct_id>NCT04422756</nct_id>
  </id_info>
  <brief_title>Prospective Evaluation of Confirmatory Testing For Primary Aldosteronism</brief_title>
  <official_title>Prospective Evaluation of Confirmatory Testing For Primary Aldosteronism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hypertension Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Calgary</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>
      This study is to evaluate the performance characteristics of the seated saline infusion test&#xD;
      and the ultra low-dose ACTH stimulation test for the diagnosis of primary aldosteronism.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective study (with a target recruitment of 200 participants) designed to&#xD;
      evaluate the performance characteristics of the seated saline infusion test and the ultra&#xD;
      low-dose ACTH stimulation test for the diagnosis of primary aldosteronism, using&#xD;
      disease-specific treatment response as a reference gold standard. Subjects consenting to&#xD;
      study participation will undergo a standardized seated saline infusion test, followed by an&#xD;
      ultra low-dose ACTH stimulation test. All participants also receive adrenal vein sampling.&#xD;
      Individuals who have unilateral disease and desire surgery will receive adrenalectomy (as&#xD;
      part of routine care) and the remaining subjects will receive medical treatment with a&#xD;
      mineralocorticoid receptor antagonist. Response to targeted treatment will be considered the&#xD;
      reference gold standard for the establishing the diagnosis of primary aldosteronism.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 15, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Diagnostic accuracy of confirmatory testing (seated saline infusion test and the ultra low-dose ACTH stimulation test)</measure>
    <time_frame>The total study timeline will occur over 66 months.</time_frame>
    <description>Measures of diagnostic accuracy, as summarized by receiver operating characteristic curve analyses.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The optimal cutoff value for confirmatory testing using clinically-important thresholds</measure>
    <time_frame>The total study timeline will occur over 66 months.</time_frame>
    <description>Plasma aldosterone</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The optimal cutoff value for confirmatory testing using clinically-important thresholds</measure>
    <time_frame>The total study timeline will occur over 66 months.</time_frame>
    <description>Aldosterone-to-renin ratio</description>
  </secondary_outcome>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Primary Aldosteronism</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Seated intravenous saline infusion test</intervention_name>
    <description>The test will be conducted by infusing two litres of normal saline intravenously over 4 hours with the patient seated.Blood collection (for aldosterone, cortisol, renin, and electrolytes) will be performed at baseline and after completion of the infusion. Following infusion, plasma aldosterone levels &lt;140 pmol/L will be considered as &quot;negative,&quot; levels &gt;280 pmol/L as &quot;positive,&quot; and levels in between classified as indeterminate.</description>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Ultra low-dose ACTH stimulation test</intervention_name>
    <description>The test will be performed by injecting 0.03 mcg of ACTH intravenously. Blood collection (for aldosterone, cortisol, and renin) will be performed at baseline and after 15 minutes. We expect a &quot;positive&quot; response to correspond with a plasma aldosterone &gt;2200 pmol/L and ARR &gt;220 pmol/L/mIU/L following stimulation.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Hypertension individuals suspected of having primary aldosteronism.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Individuals with hypertension&#xD;
&#xD;
          -  Individuals with an elevated screening adrenal renin ration (ARR)&#xD;
&#xD;
          -  Individuals with high probability features of primary aldosteronism (e.g., resistant&#xD;
             hypertension, spontaneous or diuretic-induced hypokalemia, and/or an adrenal nodule)&#xD;
             with clinical indications for adrenal vein sampling and surgery (if appropriate).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals with chronic kidney disease (estimated glomerular filtration rate &lt;40&#xD;
             mL/min/1.73m2),&#xD;
&#xD;
          -  Individuals with a history of heart failure, chronic edema, uncontrolled severe&#xD;
             hypertension (systolic blood pressure &gt;180 and/or diastolic blood pressure &gt;110 mmHg),&#xD;
             untreated hypokalemia, cortisol-secreting adrenal adenoma, and/or pheochromocytoma&#xD;
&#xD;
          -  Individual who previously received confirmatory testing.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexander Leung, Asst. Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alexander Leung, MD</last_name>
    <phone>(403) 955-8358</phone>
    <email>aacleung@ucalgary.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexander Leung, MD</last_name>
      <phone>(403) 955-8358</phone>
      <email>aacleung@ucalgary.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Leung AA, Nerenberg K, Daskalopoulou SS, McBrien K, Zarnke KB, Dasgupta K, Cloutier L, Gelfer M, Lamarre-Cliche M, Milot A, Bolli P, Tremblay G, McLean D, Tobe SW, Ruzicka M, Burns KD, Vallee M, Prasad GV, Lebel M, Feldman RD, Selby P, Pipe A, Schiffrin EL, McFarlane PA, Oh P, Hegele RA, Khara M, Wilson TW, Penner SB, Burgess E, Herman RJ, Bacon SL, Rabkin SW, Gilbert RE, Campbell TS, Grover S, Honos G, Lindsay P, Hill MD, Coutts SB, Gubitz G, Campbell NR, Moe GW, Howlett JG, Boulanger JM, Prebtani A, Larochelle P, Leiter LA, Jones C, Ogilvie RI, Woo V, Kaczorowski J, Trudeau L, Petrella RJ, Hiremath S, Drouin D, Lavoie KL, Hamet P, Fodor G, Gregoire JC, Lewanczuk R, Dresser GK, Sharma M, Reid D, Lear SA, Moullec G, Gupta M, Magee LA, Logan AG, Harris KC, Dionne J, Fournier A, Benoit G, Feber J, Poirier L, Padwal RS, Rabi DM; CHEP Guidelines Task Force. Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Can J Cardiol. 2016 May;32(5):569-88. doi: 10.1016/j.cjca.2016.02.066. Epub 2016 Mar 10.</citation>
    <PMID>27118291</PMID>
  </reference>
  <reference>
    <citation>Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10.1210/jc.2015-4061. Epub 2016 Mar 2.</citation>
    <PMID>26934393</PMID>
  </reference>
  <reference>
    <citation>Mulatero P, Milan A, Fallo F, Regolisti G, Pizzolo F, Fardella C, Mosso L, Marafetti L, Veglio F, Maccario M. Comparison of confirmatory tests for the diagnosis of primary aldosteronism. J Clin Endocrinol Metab. 2006 Jul;91(7):2618-23. doi: 10.1210/jc.2006-0078. Epub 2006 May 2.</citation>
    <PMID>16670162</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>May 9, 2023</last_update_submitted>
  <last_update_submitted_qc>May 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2023</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>Hyperaldosteronism</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04422756
org study id: REB16-2322
nct id: NCT04422756
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is to evaluate the performance characteristics of the seated saline infusion test
      and the ultra low-dose ACTH stimulation test for the diagnosis of primary aldosteronism.
This is a prospective study (with a target recruitment of 200 participants) designed to
      evaluate the performance characteristics of the seated saline infusion test and the ultra
      low-dose ACTH stimulation test for the diagnosis of primary aldosteronism, using
      disease-specific treatment response as a reference gold standard. Subjects consenting to
      study participation will undergo a standardized seated saline infusion test, followed by an
      ultra low-dose ACTH stimulation test. All participants also receive adrenal vein sampling.
      Individuals who have unilateral disease and desire surgery will receive adrenalectomy (as
      part of routine care) and the remaining subjects will receive medical treatment with a
      mineralocorticoid receptor antagonist. Response to targeted treatment will be considered the
      reference gold standard for the establishing the diagnosis of primary aldosteronism.
observational model: Cohort
time perspective: Prospective
measure: Diagnostic accuracy of confirmatory testing (seated saline infusion test and the ultra low-dose ACTH stimulation test)
time frame: The total study timeline will occur over 66 months.
description: Measures of diagnostic accuracy, as summarized by receiver operating characteristic curve analyses.
measure: The optimal cutoff value for confirmatory testing using clinically-important thresholds
time frame: The total study timeline will occur over 66 months.
description: Plasma aldosterone
measure: The optimal cutoff value for confirmatory testing using clinically-important thresholds
time frame: The total study timeline will occur over 66 months.
description: Aldosterone-to-renin ratio
intervention type: Diagnostic Test
intervention name: Seated intravenous saline infusion test
description: The test will be conducted by infusing two litres of normal saline intravenously over 4 hours with the patient seated.Blood collection (for aldosterone, cortisol, renin, and electrolytes) will be performed at baseline and after completion of the infusion. Following infusion, plasma aldosterone levels <140 pmol/L will be considered as "negative," levels >280 pmol/L as "positive," and levels in between classified as indeterminate.
intervention type: Diagnostic Test
intervention name: Ultra low-dose ACTH stimulation test
description: The test will be performed by injecting 0.03 mcg of ACTH intravenously. Blood collection (for aldosterone, cortisol, and renin) will be performed at baseline and after 15 minutes. We expect a "positive" response to correspond with a plasma aldosterone >2200 pmol/L and ARR >220 pmol/L/mIU/L following stimulation.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alexander Leung, Asst. Prof
role: Principal Investigator
affiliation: University of Calgary
last name: Alexander Leung, MD
phone: (403) 955-8358
email: aacleung@ucalgary.ca
facility: 
status: Recruiting
contact: 
country: Canada
citation: Leung AA, Nerenberg K, Daskalopoulou SS, McBrien K, Zarnke KB, Dasgupta K, Cloutier L, Gelfer M, Lamarre-Cliche M, Milot A, Bolli P, Tremblay G, McLean D, Tobe SW, Ruzicka M, Burns KD, Vallee M, Prasad GV, Lebel M, Feldman RD, Selby P, Pipe A, Schiffrin EL, McFarlane PA, Oh P, Hegele RA, Khara M, Wilson TW, Penner SB, Burgess E, Herman RJ, Bacon SL, Rabkin SW, Gilbert RE, Campbell TS, Grover S, Honos G, Lindsay P, Hill MD, Coutts SB, Gubitz G, Campbell NR, Moe GW, Howlett JG, Boulanger JM, Prebtani A, Larochelle P, Leiter LA, Jones C, Ogilvie RI, Woo V, Kaczorowski J, Trudeau L, Petrella RJ, Hiremath S, Drouin D, Lavoie KL, Hamet P, Fodor G, Gregoire JC, Lewanczuk R, Dresser GK, Sharma M, Reid D, Lear SA, Moullec G, Gupta M, Magee LA, Logan AG, Harris KC, Dionne J, Fournier A, Benoit G, Feber J, Poirier L, Padwal RS, Rabi DM; CHEP Guidelines Task Force. Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Can J Cardiol. 2016 May;32(5):569-88. doi: 10.1016/j.cjca.2016.02.066. Epub 2016 Mar 10.
PMID: 27118291
citation: Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10.1210/jc.2015-4061. Epub 2016 Mar 2.
PMID: 26934393
citation: Mulatero P, Milan A, Fallo F, Regolisti G, Pizzolo F, Fardella C, Mosso L, Marafetti L, Veglio F, Maccario M. Comparison of confirmatory tests for the diagnosis of primary aldosteronism. J Clin Endocrinol Metab. 2006 Jul;91(7):2618-23. doi: 10.1210/jc.2006-0078. Epub 2006 May 2.
PMID: 16670162
responsible party type: Sponsor
mesh term: Hyperaldosteronism
sharing ipd: No