Clinical trial NCT06740838: Overnight Dexamethasone in Primary Aldosteronism Screening
Official title: Overnight Dexamethasone in Primary Aldosteronism Screening in Patients on Interfering Therapy (the ODEPRASC Study)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Primary Aldosteronism
Hypertension
Keywords: primary aldosteronism
screening
renin
aldosterone
hypertension
corticotropin
dexamethasone
Lead sponsor: Medical University of Gdansk
Sponsor class: OTHER
First posted: 2024-12-18
Enrollment: 240
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * patients of the one-day endocrine clinic of the Department of Endocrinology and Internal Medicine of the University Clinical Center of the Medical University of Gdansk, admitted for hormonal work-up due to an adrenal lesion,
* study design is cross-sectional

Brief summary: The goal of this observational study is to learn whether screening for primary aldosteronism can be improved among patients on chronic blood pressure-lowering medications by ordering intake of 1 mg of dexamethasone prior to hormonal examinations.

Primary aldosteronism is a condition, in which an adrenal gland steroid aldosterone is released in excessive amounts; it commonly causes hypertension but requires specific therapy different from usually prescribed in other forms of hypertension.

Dexamethasone is a synthetic steroid used for both therapeutic and diagnostic purposes. A single 1 mg dexamethasone dose taken at 11 p.m. in order to measure hormone concentrations the following morning (so called overnight 1-mg dexamethasone test) is a commonly applied test in the work-up of adrenal disorders.

The main question the project aims to answer is:

Can screening for primary aldosteronism be improved among patients receiving blood pressure-lowering medications with overnight 1-mg dexamethasone intake?

Participants will undergo changes in their chronic medication to be able to definitely rule out or confirm primary aldosteronism in blood hormonal examinations. These modifications and modifications are not part of the research project.

For this project participants will be asked to

* undergo the 1-mg dexamethasone test one to three times in order to compare hormonal concentrations before and after it,
* collect urine for 24 hours to determine aldosterone in the urine sample after medications interfering in aldosterone release are temporarily withdrawn.

Detailed description: Background Primary aldosteronism (PA) underlies or contributes to hypertension (HT) in up to 30% of patients. In the last two decades PA has been demonstrated to encompass mild forms, which do not meet established diagnostic criteria, yet are still clinically relevant. However, PA has been shown to be vastly underdiagnosed: less than 5% of patients from at-risk populations undergo screening.

One of the main reasons for low PA screening prevalence is the recommendation of hypotensive therapy modification prior to hormonal assessment, i.e. withdrawal of medications interfering in the renin-angiotensin-aldosterone system (RAAS) (2016 Endocrine Society guideline, 2020 European Society of Hypertension consensus statement). On the other hand, in many instances, PA may be diagnosed despite treatment with RAAS-interfering drugs.

Previous research showed efficacy in the diagnostic approach toward PA can be greatly improved by incorporating adrenocorticotropic hormone (ACTH) suppression. This was achieved by determining PA screening and confirmatory thresholds following a 2-day 2-mg/day dexamethasone (DXM) test. Patients diagnosed with PA by meeting these novel diagnostic criteria responded well to mineralocorticoid receptor antagonists.

These two diagnostic approaches (work-up in patients receiving RAAS-interfering drugs along with ACTH suppression) have not been combined so far.

Aim To generate and temporally validate PA screening thresholds (aldosterone-to-renin ratio, ARR, and aldosterone, Ald) among patients with HT receiving medications interfering in the RAAS by applying overnight ACTH suppression.

Methodology The project received the consent of the local bioethics committee. A development cohort of n=80, and a confirmation cohort of n=80, amount to 240 participants total due to an expected withdrawal rate of 33%. Study participants will be enrolled in a single, tertiary-care endocrine hospital in one-day clinic setting among hypertensive patients undergoing hormonal examinations due to the presence of an adrenocortical lesion with radiological features of an adenoma or hyperplasia (ACA or AHA, respectively). Only patients with indications for further PA testing upon a positive, permissive ARR will be recruited for participation in the study. Further diagnostic procedures (both in the course of this research and clinically-indicated) will be conducted in an outpatient endocrine clinic. Exclusion criteria include non-viability for RAAS-interfering medication modification.

Basal (1) ARR will be required for inclusion, while in the course of the project participants will undergo ARR measurements post-DXM on own (chronic) medications (2), pre- and post-DXM ARR upon partial modification of RAAS-interfering medications (3 and 4), and pre- and post-DXM upon temporary withdrawal of RAAS-interfering medications (5 and 6). An oral salt loading test, OSLT (one of established confirmatory PA tests), will be performed off interfering medications in all patients. Also, patients with a positive PA screening result will undergo either seated saline-infusion (SIT) and/or captopril challenge test (CCT) to confirm PA in a one-day clinic. Results of these confirmatory tests will be used as reference in determining sensitivity and specificity of PA screening thresholds on RAAS-interfering therapy regimens.

Statistical analysis will be performed upon gathering clinical and hormonal data to determine thresholds for ARR, aldosterone and renin to suggest optimal (simple but more accurate than currently applied) PA screening criteria.

Expected results The hypotheses of the project are

1. Eliminating the effect of ACTH on Ald release will result in better overall accuracy of ARR (and Ald) thresholds, and
2. Complete withdrawal of RAAS-interfering medications is not required for PA screening upon ARR determination combined with ACTH suppression.

The objective of the study is demonstrating that ARR measurement following overnight 1-mg DXM intake increases the overall diagnostic accuracy in PA screening compared to conventional ARR assessment.

Eligibility criteria: Inclusion Criteria:

* suspected or diagnosed HT,
* age between 40 and 75,
* available aldosterone and renin result at the time of one-day clinic stay,
* scheduled 1-mg-DXM test (indicated for possible mild autonomous cortisol secretion, MACS),
* presence of an adrenal lesion with radiologic features of adrenocortical adenoma/hyperplasia.

Exclusion Criteria:

* baseline (pre-DXM) hyperreninemia (renin exceeding the upper limit of normal at the study site, i.e. 46.1 mIU/l, assay manufacturer: Diasorin),
* baseline (pre-DXM) Ald\<3 ng/dl,
* overt clinical and/or biochemical features of adrenal hormone deficiency or excess other than MACS (8 a.m. cortisolemia in the 50-140 nmol/l range in the 1-mg DXM test),
* therapy with glucocorticoids, non-steroidal anti-inflammatory drugs, hormonal replacement therapy, hormonal contraceptive therapy, and/or licorice intake,
* established or suspected secondary HT other than due to PA,
* comorbidities including: poorly controlled and/or other than type 2 diabetes mellitus (T2DM), present and past alcohol abuse, obesity grade 3 (i.e. body mass index of at least 40 kg/m2), severe CV disease disqualifying a patient from chronic medication modification, active malignancy, decompensated autoimmune disease as well as an autoimmune disease associated with cardiovascular and/or renal complications, estimated glomerular filtration rate (eGFR) below 45 ml/min/1.73m2, poor physical condition, lack and withdrawal of consent for participation.

Primary outcomes:
measure: Overall diagnostic accuracy of post-DXM ARR
timeFrame: 24 months
Secondary outcomes:
measure: Association between post-DXM ARR and 24-h urinary aldosteronuria in the oral salt loading test
timeFrame: 24 months
Other outcomes:
Locations:
city: Gdansk
country: Poland
facility: Department of Endocrinology and Internal Medicine, University Clinical Center, Medical University of Gdansk
state: Pomorskie
Study officials:
affiliation: Department of Endocrinology and Internal Medicine, Medical University of Gdansk
name: Piotr Kmiec, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
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