11C-Metomidate PET/CT for Endocrine Hypertension and Characterisation of Adrenal Tumours

Changi General Hospital

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Primary Aldosteronism Due to Aldosterone Producing Adenoma; Primary Aldosteronism; Adrenal Tumors

Treatments: Combination Product: 11C-Metomidate PET/CT imaging at Clinical Imaging Research Centre

Study type: Interventional

Funder types: Other

Identifiers

NCT06100367

PA_MTO (Other Grant/Funding Number)

Details and patient eligibility

About

• 10% of patients with hypertension potentially have the treatable condition - primary aldosteronism (PA). This is caused by either bilateral adrenal disease (~40%), managed with lifelong medications; or unilateral disease (~60%), cured with laparoscopic surgery (adrenalectomy). Current diagnosis of PA includes a screening test with aldosterone-renin ratio, followed by a confirmatory salt loading test (in most patients) to demonstrate unsuppressed aldosterone levels. Of note, some patients with suppressed aldosterone after confirmatory tests (also termed low-renin hypertension) may also have unilateral adrenal tumors.
• The difficulty with identifying curable unilateral disease is due to adrenal vein sampling (AVS): an invasive, and technically-difficult procedure. An alternative novel imaging, 11C-Metomidate Positron emission tomography-computed tomography (PET-CT), can detect adrenal tumors which are over-producing aldosterone. It is non-invasive, non-operator-dependent, and potentially may identify more patients with curable unilateral disease. The results from our pilot study in 25 patients with confirmed PA (ClinicalTrials.gov NCT03990701, PA_CURE) showed that 11C-Metomidate PET-CT exhibited comparable performance to AVS in subtyping PA, and this should be validated in a larger study.
• In addition, 11C-Metomidate is also able to differentiate adrenocortical lesions in the adrenal gland from other lesions found in adrenal tissue, such as adrenomedullary lesions (e.g. pheochromocytoma).
• Hence, the investigators hypothesize that 11C-metomidate PET-CT can accurately (1) identify patients with surgically curable unilateral adrenal disease among hypertensive Asians with primary aldosteronism (PA_CURE 2 / PA_MTO EH study) and (2) differentiate adrenocortical lesions from other lesions in patients with adrenal tumors (PA_MTO AT study)

Full description

• The investigators aim to recruit 100 patients with confirmed, or likely, primary aldosteronism to undergo conventional tests, CT, AVS, and 11C-metomidate PET-CT.
• Results will be reviewed and discussed at a multidisciplinary meeting, and patients with unilateral PA or adrenal tumor will be offered surgery. Patients will be reviewed 6 months post-surgery.
• In a separate study, the investigators will recruit 10 patients with adrenal tumors to differentiate adrenocortical lesions from other lesions in patients with adrenal tumors

Enrollment: 100 estimated patients

Sex: All

Ages: 21 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• For patients with primary aldosteronism (PA_CURE 2 / PA_MTO EH):

  1. Confirmed diagnosis of 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; or likely primary aldosteronism / low-renin hypertension (inappropriate aldosterone levels and suppressed renin levels)
  2. Keen for surgical treatment if shown to have unilateral adrenal disease.

• For patients with suspected adrenal tumors (PA_MTO AT)

  1. All patients with suspected adrenal tumors based on imaging and clinical suspicion.

Exclusion criteria

• Inability to provide written informed consent.
• Chronic renal failure of Stage 3b or greater severity, estimated glomerular filtration rate (eGFR) < 45ml/min/1.73m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. (only applicable for PA_CURE 2 / PA_MTO EH)
• Severe or terminal medical condition(s) that in the view of the investigator prohibits participation in the study or interferes with possible treatment or health-related quality of life, e.g. cancer, end-stage liver disease, end stage renal failure (only applicable for PA_CURE 2 / PA_MTO EH)
• Contraindications to isotope scanning (e.g. Female patients who are pregnant (self-declared or via positive pregnancy test), intending to become pregnant (within 3 months of scan) or breastfeeding) or CT Scan, which includes but not limited to waist circumference >140cm, morbid obesity or claustrophobia (limiting entry in CT scanner)
• Contraindication to ingestion of corticosteroids (e.g. poorly controlled diabetes, HbA1C >13%)

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

11C-metomidate PET-CT

Experimental group

Description:

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 100 - 300 Megabecquerel (MBq) (11C-metomidate) to identify functional unilateral adrenal disease

Treatment:

Combination Product: 11C-Metomidate PET/CT imaging at Clinical Imaging Research Centre