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

Phase 2
Recruiting
Conditions
Primary Aldosteronism
Adrenal Tumors
Primary Aldosteronism Due to Aldosterone Producing Adenoma
Interventions
Combination Product: 11C-Metomidate PET/CT imaging at Clinical Imaging Research Centre
Registration Number
NCT06100367
Lead Sponsor
Changi General Hospital
Brief Summary

* 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)

Detailed 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

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
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%)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
11C-metomidate PET-CT11C-Metomidate PET/CT imaging at Clinical Imaging Research CentreAll 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
Primary Outcome Measures
NameTimeMethod
Biochemical outcome of unilateral primary aldosteronism based on the Primary Aldosteronism Surgical Outcome (PASO) criteria (PA_CURE 2 / PA_MTO EH study).6 months

The number of patients with complete, partial, and absent biochemical success according to the PASO criteria.

Diagnostic performance of 11C-Metomidate PET-CT in identifying unilateral adrenocortical tumor (PA_MTO AT study).6 months

Percentage of patients accurately identified with adrenocortical tumor using 11C-Metomidate PET-CT, when compared to the histopathology of the excised tumor. In patients who have not undergone surgery, this will be determined by clinical diagnosis.

Secondary Outcome Measures
NameTimeMethod
Cost-effectiveness of 11C-Metomidate PET-CT versus AVS in diagnosing patients with unilateral primary aldosteronism (PA_CURE 2 / PA_MTO EH STUDY).6 months

Cost-effectiveness of the diagnostic course will be calculated by using calculated costs per quality-adjusted life years (QALYs).

Diagnostic criteria using 11C-metomidate PET/CT (PA_CURE 2 / PA_MTO EH study).6 months

The cut-off level of maximum standard update value (SUVmax) values which offer the best sensitivity and specificity for lateralization of aldosterone-producing adenoma in 11C-metomidate PET/CT.

Diagnostic performance of 11C-Metomidate PET-CT in identifying unilateral aldosterone-producing adenoma (PA_CURE 2 / PA_MTO EH study).6 months

Percentage of patients accurately identified with unilateral PA using 11C-Metomidate PET-CT and AVS, as compared to histopathology of the excised tumor (defined as 'Classical' single, functioning aldosterone-producing adenoma using HISTopathological classification by the Histopathology of primary ALDOsteronism (HISTALDO) consensus).

Clinical outcome of unilateral primary aldosteronism based on the Primary Aldosteronism Surgical Outcome (PASO) criteria (PA_CURE 2 / PA_MTO EH STUDY).6 months

The number of patients with complete, partial, and absent clinical success according to the PASO criteria.

Number of patients with low-renin hypertension with unilateral adrenal tumors (PA_CURE 2 / PA_MTO EH study).6 months

Quantify the number of patients with low-renin hypertension or only obtain borderline diagnostic criteria for PA but have unilateral adrenal lesions detected on 11C-metomidate PET/CT.

Trial Locations

Locations (7)

Ng Teng Fong General Hospital

🇸🇬

Singapore, Singapore

Singapore General Hospital

🇸🇬

Singapore, Singapore

National University Hospital

🇸🇬

Singapore, Singapore

Sengkang General Hospital

🇸🇬

Singapore, Singapore

Tan Tock Seng Hospital

🇸🇬

Singapore, Singapore

Khoo Teck Puat Hospital

🇸🇬

Singapore, Singapore

Changi General Hospital

🇸🇬

Singapore, Singapore

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