Primary Aldosteronism and Surgically Curable Forms in Hypertension Patients Using 11C-Metomidate

10% of patients with hypertension potentially have the treatable condition - primary aldosteronism. Primary aldosteronism (PA) is caused by either bilateral adrenal disease (~40%), managed with lifelong medications; or unilateral disease (~60%), cured with laparoscopic surgery (adrenalectomy). Unfortunately, many patients with curable hypertension remain undiagnosed and consequently develop cardiac disease and strokes. The difficulty with identifying curable unilateral disease is due to adrenal vein sampling (AVS): an invasive, and technically-difficult procedure, with inconclusive results in 50% of patients. An alternative novel imaging, 11C-metomidate Positron emission tomography-computed tomography (PET-CT), can detect adrenal tumors, and concurrently confirm their over-activity. It is non-invasive, non-operator-dependent, and can identify more patients with curable hypertension.

Investigators hypothesize that 11C-metomidate PET-CT can accurately identify patients with surgically-curable unilateral adrenal disease among hypertensive Asians with primary aldosteronism.

Study Overview

• Status: Completed
• Conditions: Primary Aldosteronism; Primary Aldosteronism Due to Aldosterone Producing Adenoma
• Intervention / Treatment: Combination product: 11C-Metomidate PET/CT Scan

Detailed Description

25 patients with confirmed PA who are keen for a surgical cure if unilateral PA is confirmed, will undergo conventional tests, CT, AVS, as well as 11C-metomidate PET/CT.

Results will be reviewed and discussed at a multidisciplinary meeting, and patients with unilateral PA will be offered surgery. Patients will be reviewed 6 months post surgery to assess for cure of PA.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 529889
    • Changi General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary aldosteronism, as defined in Endocrine Society Guidelines 2016, with positive confirmatory test (post-salt loading aldosterone >140pmol/L); or hypokalemia with undetectable renin levels and aldosterone >550pmol/L.

Exclusion Criteria:

• Inability to provide written informed consent
• < 21 years or > 70 years
• Chronic renal failure of Stage 3b or greater severity
• Severe or terminal medical condition(s)
• Contraindications to isotope scanning or CT Scan
• Contraindication to ingestion of corticosteroids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; All patients will undergo standard-of-care investigations (CT imaging of adrenals and AVS) and the research test (11C-metomidate PET-CT) with a dose of 150 - 300 Megabecquerel (MBq) (11C-metomidate) to identify functional unilateral adrenal disease.	Combination product: 11C-Metomidate PET/CT Scan; 11C-Metomidate PET/CT imaging at Clinical Imaging Research Centre

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure of Primary Aldosteronism Post-Adrenalectomy	Percentage of patients accurately identified with unilateral PA (determined by post-surgery biochemical cure) using 11C-metomidate PET/CT compared to percentage of patients accurately identified with unilateral PA (determined by post-surgery biochemical cure) using AVS	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Diagnosis of Unilateral Primary Aldosteronism	Percentage of patients accurately identified with unilateral PA (determined by clinical diagnosis made by multidisciplinary team) using 11C-metomidate PET/CT compared to percentage of patients accurately identified with unilateral PA (determined by clinical diagnosis made by multidisciplinary team) using AVS	6 months
Cost-Effectiveness of Diagnostic Test	Cost-Effectiveness of Diagnostic Test to identify unilateral PA	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic criteria using 11C-Metomidate PET/CT	To assess the cut-off level of SUVmax which offers the best sensitivity and specificity for lateralisation in 11C-metomidate PET-CT	6 months

Collaborators and Investigators

• Sponsor: Changi General Hospital
• Collaborators: Khoo Teck Puat Hospital; Singapore General Hospital; Tan Tock Seng Hospital; National University Health System, Singapore; Ng Teng Fong General Hospital; Clinical Imaging Research Centre

Publications and helpful links

General Publications

• Puar TH, Khoo CM, Tan CJ, Tong AKT, Tan MCS, Teo AE, Ng KS, Wong KM, Reilhac A, O'Doherty J, Gomez-Sanchez CE, Kek PC, Yee S, Tan AWK, Chuah MB, Lee DHM, Wang KW, Zheng CQ, Shi L, Robins EG, Foo RSY; PA CURE investigators. 11C-Metomidate PET-CT versus adrenal vein sampling to subtype primary aldosteronism: a prospective clinical trial. J Hypertens. 2022 Jun 1;40(6):1179-1188. doi: 10.1097/HJH.0000000000003132.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2018
• Primary Completion (Actual): March 30, 2021
• Study Completion (Actual): March 30, 2021

Study Registration Dates

• First Submitted: December 19, 2018
• First Submitted That Met QC Criteria: June 16, 2019
• First Posted (Actual): June 19, 2019

Study Record Updates

• Last Update Posted (Actual): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 28, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Hypertension; Adrenalectomy; 11-C Metomidate PET/CT; Adrenal Vein Sampling; Subtyping
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Hypertension; Adenoma; Hyperaldosteronism; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Metomidate
• Other Study ID Numbers: PA_CURE

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