Dynamic Hormone Profiling and Multimodal Data Capture in Primary Aldosteronism

This study is a observational study applying 24-hour microdialysis methodology to perform dynamic multisteroid adrenal hormone profiling of patients with suspected or confirmed PA. Simultaneous registration of blood pressure, tissue glucose, sleep pattern, activity level and food intake registration may be performed. The overall objective is to develop a novel, sensitive, fast and user-friendly diagnostic procedure for PA, using multimodal data capture including dynamic multisteroid hormone profiling from microdialysis fluid.

Study Overview

• Status: Recruiting
• Conditions: Primary Aldosteronism; Mineralocorticoid Excess; Hypercortisolism
• Intervention / Treatment: Device: dynamic microdialysis sampling

Detailed Description

Primary aldosteronism is the most common cause of secondary hypertension. Primary aldosteronism has increased risk of organ complications compared with primary hypertension if left undiagnosed and without specific treatment. However, the current diagnostic work-up is a cumbersome, multistep process, relying on repeated single time point measurements of aldosterone, not capturing the rhythmic nature of aldosterone and related adrenal hormone secretion.

In this study we will apply the U-Rhythm microdialysis sampling system for 24-hour measurements from subcutaneous microdialysis fluid, analysed with LC/MS-MS methodology for dynamic multisteroid adrenal hormone profiling. We will further compare multisteroid hormone profiling results with variations in blood pressure and tissue glucose, sleep pattern, activity level and food intake.

The overall objective of the study is to develop a novel, sensitive, fast and user-friendly diagnostic procedure for PA, using multimodal data capture including 24-hour dynamic multisteroid hormone profiling from microdialysis tissue.

Primary objective

• Assess dynamic multisteroid rhythmicity in microdialysis fluid of aldosterone, precursors and metabolites of the mineralocorticoid and glucocorticoid pathway, compared to standard diagnostic work-up in patients with suspected or confirmed PA.

Secondary objectives

• Quantify the influence of salt and volume loading during diagnostic saline infusion test on multisteroid adrenal rhythmicity.
• Quantify the influence of glucocorticoids/ACTH suppression on multisteroid rhythmicity.
• Quantify the influence of cortisol co-secretion on multisteroid rhythmicity in PA.
• Quantify influence of blood pressure, pulse, sleep, food intake and movement on multisteroid rhythmicity in PA.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Marianne Aardal Grytaas, MD PhD; Phone Number: 004741545435; Email: marianne.grytaas@helse-bergen.no
• Study Contact Backup: Name: Kristian Løvås, MD PhD; Phone Number: 004791113955; Email: kristian.lovas@helse-bergen.no

Study Locations

• Norway
  • Bergen, Norway, 5021
    • Recruiting
    • Haukeland University Hospital
    • Contact: Marianne Grytaas, MD phd; Phone Number: +4741545435; Email: marianne.grytaas@helse-bergen.no
    • Contact: Kristian Løvås, MD Phd; Email: kristian.lovas@helse-bergen.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with suspected primary aldosteronism admitted to Haukeland University for diagnostic saline infusion test will be invited for study inclusion for dynamic microdialysis during saline infusion testing. If the diagnosis is confirmed, a repeated microdialysis sampling will be performed without saline infusion suppression.

Additional patients with confirmed primary aldosteronism admitted to Haukeland University Hospital for subtyping with adrenal vein sampling will be invited for study inclusion for microdialysis without and during dexamethasone suppression.

Description

Inclusion criteria Age 18 to 70 years Suspected PA admitted for diagnostic saline infusion testing or confirmed PA diagnosis according to Endocrine Society criteria.. Written informed consent

Exclusion criteria

• Age <18 or > 70 years.
• Pregnancy.
• Known adrenal failure and/or on steroid therapy (oral, inhaled, parenteral or topical) or other interfering medication.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Primary aldosteronism; Patients with suspected and/or confirmed primary aldosteronism, aged 18-70 years

Device: dynamic microdialysis sampling; Included patients will perform 24-hour dynamic microdialysis sampling from subcutaneous tissue fluid of the lower abdomen, applying the U-Rhythm sampler. Simutaneous measurements of blood pressure, glucose, and registration of activity level, meals and sleep pattern during microdialysis sampling may be performed. Microdialysis sampling will be performed during various conditions: during daily life activities, during saline infusion suppression testing and during dexamethasone suppression testing. Repeated sampling may be performed post treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multisteroid rhythmicity of mineralocorticoids and glucocorticoids in primary aldosteronism	Assess multisteroid rhythmicity measured in microdialysis fluid of aldosterone, precursors and metabolites of the mineralocorticoid and glucocorticoid pathway, compared to standard diagnostic work-up in patients with suspected or confirmed PA.	2024-2028

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of saline infusion test on multisteroid rhythmicity of mineralocorticoids and glucocorticoids	Influence of diagnostic saline infusion test on multisteroid adrenal rhythmicity will be assessed by performing 24h microdialysis before and during saling infusion testing	2024-2028
Effect of exogenous glucocorticoid suppression on aldosterone rhythmicity	Influence of exogenous administered glucocorticoids on aldosterone and related adrenal hormone rhythmicity will be assessed by performing 24h microdilays without and during suppression with exogenous glucocorticoids	2024-2028
cortisol co-secretion in primary aldosteronism	determine and quantify the presence of cortisol co-secretion in primary aldosteronism assessed by dynamic microdialysis compared with conventional cortisol co-secretion testing	2024-2028
Blood pressure, glucose and sleeep pattern correlation to dynamic hormone rhythmicity in primary aldosteronism	Correlate continous blood pressure and glucose variations, sleep, food intake and movement to variations in multisteroid hormone rhythmicity in primary aldosteronism.	2024-2028

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Collaborators: University of Bergen
• Investigators: Principal Investigator: Marianne Aarda Grytaas, MD PhD, Haukeland University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 3, 2024
• First Submitted That Met QC Criteria: July 3, 2024
• First Posted (Actual): July 11, 2024

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 3, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: aldosterone
• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Hyperaldosteronism; Cushing Syndrome; Adrenocortical Hyperfunction
• Other Study ID Numbers: REK 729178

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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