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

NCT ID: NCT06569589

Last Updated: 2025-06-06

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-12-27
• Study Completion Date: 2026-08-31

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.

Conditions

Hypertension; Primary Aldosteronism; Hypokalemia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Suspected PA

Age 21-70 years, with arterial hypertension or suspected to have primary aldosteronism based on Endocrine Society Guidelines.

23NaMRI Scan

Intervention Type: DIAGNOSTIC_TEST

23NaMRI, a non-invasive detection and quantification of hidden tissue Na+ stores in humans.

Potassium Chloride (KCl)

Intervention Type: DIETARY_SUPPLEMENT

K+ supplementation intervention is given participants as part of their standard care. In this trial the K+ supplementation dosage is standardized and adjusted based on blood K+ level

Interventions

23NaMRI Scan

23NaMRI, a non-invasive detection and quantification of hidden tissue Na+ stores in humans.

Intervention Type: DIAGNOSTIC_TEST

Potassium Chloride (KCl)

K+ supplementation intervention is given participants as part of their standard care. In this trial the K+ supplementation dosage is standardized and adjusted based on blood K+ level

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Changi General Hospital

OTHER

Sponsor Role: collaborator

Singapore General Hospital

OTHER

Sponsor Role: collaborator

Sengkang General Hospital

OTHER

Sponsor Role: collaborator

Jens Titze

OTHER

Sponsor Role: lead

Responsible Party

Jens Titze

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jens Titze, MD

Role: PRINCIPAL_INVESTIGATOR

Duke-NUS Graduate Medical School

Locations

Singapore General Hospital

Singapore, , Singapore

Site Status: NOT_YET_RECRUITING

Duke NUS Medical School

Singapore, , Singapore

Site Status: RECRUITING

Changi General Hospital

Singapore, , Singapore

Site Status: RECRUITING

Sengkang General Hospital

Singapore, , Singapore

Site Status: NOT_YET_RECRUITING

Countries

Singapore

Central Contacts

Tzy Tiing Lim

Role: CONTACT

tzytiing.lim@duke-nus.edu.sg

+65 6516 7666

Marton Adriana, MD

Role: CONTACT

adriana.marton@duke-nus.edu.sg

Facility Contacts

Joanna Teo

Role: primary

Teo_Hwee_Ling@cgh.com.sg

Tzy Tiing Lim

Role: primary

tzytiing.lim@duke-nus.edu.sg

Joanna Teo

Role: primary

Teo_Hwee_Ling@cgh.com.sg

Joanna Teo

Role: primary

Teo_Hwee_Ling@cgh.com.sg

References

Kopp C, Linz P, Wachsmuth L, Dahlmann A, Horbach T, Schofl C, Renz W, Santoro D, Niendorf T, Muller DN, Neininger M, Cavallaro A, Eckardt KU, Schmieder RE, Luft FC, Uder M, Titze J. (23)Na magnetic resonance imaging of tissue sodium. Hypertension. 2012 Jan;59(1):167-72. doi: 10.1161/HYPERTENSIONAHA.111.183517. Epub 2011 Dec 5.

Reference Type: BACKGROUND

PMID: 22146510 (View on PubMed)

Kopp C, Linz P, Dahlmann A, Hammon M, Jantsch J, Muller DN, Schmieder RE, Cavallaro A, Eckardt KU, Uder M, Luft FC, Titze J. 23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients. Hypertension. 2013 Mar;61(3):635-40. doi: 10.1161/HYPERTENSIONAHA.111.00566. Epub 2013 Jan 21.

Reference Type: BACKGROUND

PMID: 23339169 (View on PubMed)

Marton A, Saffari SE, Rauh M, Sun RN, Nagel AM, Linz P, Lim TT, Takase-Minegishi K, Pajarillaga A, Saw S, Morisawa N, Yam WK, Minegishi S, Totman JJ, Teo S, Teo LLY, Ng CT, Kitada K, Wild J, Kovalik JP, Luft FC, Greasley PJ, Chin CWL, Sim DKL, Titze J. Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure. J Am Coll Cardiol. 2024 Apr 16;83(15):1386-1398. doi: 10.1016/j.jacc.2024.02.020.

Reference Type: BACKGROUND

PMID: 38599715 (View on PubMed)

Other Identifiers

2023-1047

Identifier Type: -

Identifier Source: org_study_id