Prospective Evaluation of Confirmatory Testing For Primary Aldosteronism

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.

Study Overview

• Status: Recruiting
• Conditions: Primary Aldosteronism
• Intervention / Treatment: Diagnostic test: Seated intravenous saline infusion test; Diagnostic test: Ultra low-dose ACTH stimulation test

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Alexander Leung, MD; Phone Number: (403) 955-8358; Email: aacleung@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Recruiting
      • University of Calgary
      • Contact: Alexander Leung, MD; Phone Number: (403) 955-8358; Email: aacleung@ucalgary.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Hypertension individuals suspected of having primary aldosteronism.

Description

Inclusion Criteria:

• Individuals with hypertension
• Individuals with an elevated screening adrenal renin ration (ARR)
• Individuals with high probability features of primary aldosteronism (e.g., resistant hypertension, spontaneous or diuretic-induced hypokalemia, and/or an adrenal nodule) with clinical indications for adrenal vein sampling and surgery (if appropriate).

Exclusion Criteria:

• Individuals with chronic kidney disease (estimated glomerular filtration rate <40 mL/min/1.73m2),
• Individuals with a history of heart failure, chronic edema, uncontrolled severe hypertension (systolic blood pressure >180 and/or diastolic blood pressure >110 mmHg), untreated hypokalemia, cortisol-secreting adrenal adenoma, and/or pheochromocytoma
• Individual who previously received confirmatory testing.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of confirmatory testing (seated saline infusion test and the ultra low-dose ACTH stimulation test)	Measures of diagnostic accuracy, as summarized by receiver operating characteristic curve analyses.	The total study timeline will occur over 66 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The optimal cutoff value for confirmatory testing using clinically-important thresholds	Plasma aldosterone	The total study timeline will occur over 66 months.
The optimal cutoff value for confirmatory testing using clinically-important thresholds	Aldosterone-to-renin ratio	The total study timeline will occur over 66 months.

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Canadian Institutes of Health Research (CIHR); Hypertension Canada
• Investigators: Principal Investigator: Alexander Leung, Asst. Prof, University of Calgary

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2017
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Hyperaldosteronism
• Other Study ID Numbers: REB16-2322

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No