Tissue Sodium Quantification in Patients With Primary Aldosteronism: See Sodium to Treat

Recruiting

• Conditions: Hypertension; Primary Aldosteronism
• Interventions: Diagnostic Test: 23NaMRI Scan

• Registration Number: NCT06569589
• Lead Sponsor: Jens Titze

Brief Summary

The study aims to provide quantitative facts on the pathophysiological changes in tissue Na+ content during Na+/K+ redistribution disorders in patients with PA in response to standard therapy. The investigators hypothesize that patients with primary aldosteronism have excessive Na+ storage in the muscle, which can now be quantified non-invasively using 23NaMRI. In analogy to the role of HbA1c as a metabolic long-term marker in diabetes, the quantifiable changes in muscle Na+ content may deliver the data evidence necessary to justify and conduct randomized diagnostic endpoint outcome trials in the future, with the ultimate aim to improve PA detection rate and treatment.

Detailed Description

Arterial hypertension is a major modifiable cardiovascular risk factor along with diabetes mellitus. Hypertension due to autonomous elevation in aldosterone production (Primary Aldosteronism; PA) is not responsive to usual antihypertensive medications and is dramatically underdiagnosed in standard clinical routine. Currently, only 0.1% (1,280,000 worldwide and 1,140 Singaporeans) are diagnosed, much lower than the 5-20% (64,000,000-256,000,000 worldwide and 57,000-228,000 Singaporeans) of all patients with arterial hypertension estimated to suffer from PA. Given the high prevalence of PA, low rates of diagnoses, high cardiometabolic morbidity and mortality associated with untreated PA, the detection of more patients with PA is obligatory, and treatment success must be monitored.

The investigators hypothesize that patients with primary aldosteronism have excessive Na+ storage in the muscle, which can now be quantified non-invasively using 23NaMRI. This study will be the first to systematically quantify changes in muscle Na+ stores in these patients in response to standard therapy. There is currently no established clinical diagnostic tool to detect or quantify the underlying cellular Na+/K+ redistribution physiology in patients with PA. Seeing and quantifying the Na+ non-invasively with 23NaMRI will provide a fresh "look" into the pathophysiological principles of solute and fluid homeostasis to evaluate therapy efficacy, and to improve rates of PA diagnoses with an intention to cure.

This is a prospective non-randomized multi-centre study with 3 study visits ( pre-potassium treatment, pre- diagnosis and post-treatment) over a study period of 3 years. Approximately 100 participants will be recruited from hospital sites. The purpose of the study is to detect and quantify a hidden pathophysiological Na+/K+ redistribution process at the tissue level, using 23NaMRI, in an effort to provide an alternative to traditional hormone and solute diagnostics in blood and urine.

Study Timeline

• Study Start: 2023-12-27
• Status Verified: 2024-08
• Study First Submitted: 2024-08-01
• Study First Submitted QC: 2024-08-21
• Last Update Submitted: 2024-08-21
• Study First Posted: 2024-08-26
• Last Update Posted: 2024-08-26
• Primary Completion: 2026-03-31
• Study Completion: 2026-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Age 21-70 years, with arterial hypertension or suspected to have primary aldosteronism based on Endocrine Society Guidelines.
2. Male and female patients older than 21 years.
3. Willingness to participate and ability to provide informed consent.

Exclusion Criteria

1. Patients with exclusion criteria for the MRI, such as:

   • implanted devices (surgical clips, heart pacemakers or defibrillators, cochlear implants)
   • iron-based tattoos
   • any other pieces of metal or devices that are not MR-Safe anywhere in the body
   • patients who exhibit noticeable anxiety and/or claustrophobia into the MRI scanner
   • pregnancy

2. Diagnosis of heart failure NYHA classes III and IV

3. Impaired renal function with eGFR<30 ml/min or proteinuria > 1 g/24h

4. Liver disease with cirrhosis (Child-Pugh class C) or hypoalbuminemia

5. Muscular dystrophies

6. Patients with active cancer or severe comorbid conditions likely to compromise survival or study participation

7. Unwillingness or other inability to cooperate

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Suspected PA	23NaMRI Scan	Age 21-70 years, with arterial hypertension or suspected to have primary aldosteronism based on Endocrine Society Guidelines.

Primary Outcome Measures

Name	Time	Method
Patients with primary aldosteronism have a 10-20% higher muscle Na+ content compared to healthy controls	Baseline	Difference in muscle Na+ content as measured with 23NaMRI between patients with PA and healthy controls at baseline.

Secondary Outcome Measures

Name	Time	Method
High K+ intake reduces muscle Na+ in patients with primary aldosteronism	Baseline to 3 Months	Change in muscle Na+ content as measured with 23NaMRI, 3 months after initiation of K+ supplementation
MR blockade reduces muscle Na+ conten in patients with primary aldosteronism	Baseline to 18 months	Change in muscle Na+ content as measured with 23NaMRI, 12-18 months after initiation of MR blockade treatment
Compared to MR blockade, adenoma surgical removal is more efficient in reducing muscle Na+ in patients with primary aldosteronism	36 Months	Change in muscle Na+ content as measured with 23NaMRI after adenoma surgical removal compared to MR blockade treatment.

Trial Locations

Locations (4)

Duke NUS Medical School; 🇸🇬 Singapore, Singapore

Sengkang General Hospital; 🇸🇬 Singapore, Singapore

Changi General Hospital; 🇸🇬 Singapore, Singapore

Singapore General Hospital; 🇸🇬 Singapore, Singapore