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

Primary Purpose

Primary Aldosteronism Due to Aldosterone Producing Adenoma, Primary Aldosteronism, Adrenal Tumors

Status
Recruiting
Phase
Phase 2
Locations
Singapore
Study Type
Interventional
Intervention
11C-Metomidate PET/CT imaging at Clinical Imaging Research Centre
Sponsored by
Changi General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Primary Aldosteronism Due to Aldosterone Producing Adenoma focused on measuring 11-C Metomidate PET/CT, Functional imaging, Secondary / Endocrine hypertension, Adrenal Vein Sampling, Subtyping; localization testing, Adrenalectomy

Eligibility Criteria

21 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: For patients with primary aldosteronism (PA_CURE 2 / PA_MTO EH): 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) Keen for surgical treatment if shown to have unilateral adrenal disease. For patients with suspected adrenal tumors (PA_MTO AT) 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%)

Sites / Locations

  • Changi General HospitalRecruiting
  • Khoo Teck Puat HospitalRecruiting
  • National University HospitalRecruiting
  • Ng Teng Fong General HospitalRecruiting
  • Sengkang General HospitalRecruiting
  • Singapore General HospitalRecruiting
  • Tan Tock Seng HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental: Single Arm

Arm 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

Outcomes

Primary Outcome Measures

Biochemical outcome of unilateral primary aldosteronism based on the Primary Aldosteronism Surgical Outcome (PASO) criteria (PA_CURE 2 / PA_MTO EH study).
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).
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

Clinical outcome of unilateral primary aldosteronism based on the Primary Aldosteronism Surgical Outcome (PASO) criteria (PA_CURE 2 / PA_MTO EH STUDY).
The number of patients with complete, partial, and absent clinical success according to the PASO criteria.
Diagnostic performance of 11C-Metomidate PET-CT in identifying unilateral aldosterone-producing adenoma (PA_CURE 2 / PA_MTO EH study).
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).
Cost-effectiveness of 11C-Metomidate PET-CT versus AVS in diagnosing patients with unilateral primary aldosteronism (PA_CURE 2 / PA_MTO EH STUDY).
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).
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.
Number of patients with low-renin hypertension with unilateral adrenal tumors (PA_CURE 2 / PA_MTO EH study).
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.

Full Information

First Posted
October 13, 2023
Last Updated
October 19, 2023
Sponsor
Changi General Hospital
Collaborators
National University Health System, Singapore, Clinical Imaging Research Centre, Singapore General Hospital, Tan Tock Seng Hospital, Khoo Teck Puat Hospital, Ng Teng Fong General Hospital, Sengkang General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT06100367
Brief Title
11C-Metomidate PET/CT for Endocrine Hypertension and Characterisation of Adrenal Tumours
Official Title
11C-Metomidate PET/CT for Endocrine Hypertension and Characterisation of Adrenal Tumours
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 30, 2019 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
July 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Changi General Hospital
Collaborators
National University Health System, Singapore, Clinical Imaging Research Centre, Singapore General Hospital, Tan Tock Seng Hospital, Khoo Teck Puat Hospital, Ng Teng Fong General Hospital, Sengkang General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Aldosteronism Due to Aldosterone Producing Adenoma, Primary Aldosteronism, Adrenal Tumors
Keywords
11-C Metomidate PET/CT, Functional imaging, Secondary / Endocrine hypertension, Adrenal Vein Sampling, Subtyping; localization testing, Adrenalectomy

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Model Description
11C-metomidate synthesis will be done at Clinical Imaging Research Centre in compliance with good manufacturing practice using a General Electric Medical Systems PET trace 860 cyclotron. Non-contrast CT images will be acquired over the adrenal. After an intravenous injection of 11C-metomidate, PET images will be acquired. Attenuation and decay-corrected images will be converted to standardized uptake value (SUV) maps through division by (injected activity per patient weight). The maximum SUV values over regions of interest will be determined for 10-min static images starting 35 min after the injection.
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: Single Arm
Arm Type
Experimental
Arm 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
Intervention Type
Combination Product
Intervention Name(s)
11C-Metomidate PET/CT imaging at Clinical Imaging Research Centre
Intervention Description
11C-Metomidate PET/CT imaging at Clinical Imaging Research Centre
Primary Outcome Measure Information:
Title
Biochemical outcome of unilateral primary aldosteronism based on the Primary Aldosteronism Surgical Outcome (PASO) criteria (PA_CURE 2 / PA_MTO EH study).
Description
The number of patients with complete, partial, and absent biochemical success according to the PASO criteria.
Time Frame
6 months
Title
Diagnostic performance of 11C-Metomidate PET-CT in identifying unilateral adrenocortical tumor (PA_MTO AT study).
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Clinical outcome of unilateral primary aldosteronism based on the Primary Aldosteronism Surgical Outcome (PASO) criteria (PA_CURE 2 / PA_MTO EH STUDY).
Description
The number of patients with complete, partial, and absent clinical success according to the PASO criteria.
Time Frame
6 months
Title
Diagnostic performance of 11C-Metomidate PET-CT in identifying unilateral aldosterone-producing adenoma (PA_CURE 2 / PA_MTO EH study).
Description
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).
Time Frame
6 months
Title
Cost-effectiveness of 11C-Metomidate PET-CT versus AVS in diagnosing patients with unilateral primary aldosteronism (PA_CURE 2 / PA_MTO EH STUDY).
Description
Cost-effectiveness of the diagnostic course will be calculated by using calculated costs per quality-adjusted life years (QALYs).
Time Frame
6 months
Title
Diagnostic criteria using 11C-metomidate PET/CT (PA_CURE 2 / PA_MTO EH study).
Description
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.
Time Frame
6 months
Title
Number of patients with low-renin hypertension with unilateral adrenal tumors (PA_CURE 2 / PA_MTO EH study).
Description
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.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: For patients with primary aldosteronism (PA_CURE 2 / PA_MTO EH): 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) Keen for surgical treatment if shown to have unilateral adrenal disease. For patients with suspected adrenal tumors (PA_MTO AT) 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%)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Troy Puar Hai Kiat, MRCP, PHD
Phone
64267818
Email
troy.puar.h.k@singhealth.com.sg
First Name & Middle Initial & Last Name or Official Title & Degree
Geraldine Lim
Phone
64267818
Email
geraldine.lim.x@singhealth.com.sg
Facility Information:
Facility Name
Changi General Hospital
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr Troy Puar Hai Kiat
Phone
64267818
Email
troy.puar.h.k@singhealth.com.sg
Facility Name
Khoo Teck Puat Hospital
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr Daphne Lee Hui Min
Phone
65558000
Email
lee.daphne.hm@ktph.com.sg
Facility Name
National University Hospital
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Prof Roger Foo
Phone
67723381
Email
roger.foo@nus.edu.sg
Facility Name
Ng Teng Fong General Hospital
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr Yee Szemen
Phone
67162000
Email
yee_szemen@nuhs.edu.sg
Facility Name
Sengkang General Hospital
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr Chuah Bingfeng Matthew
Phone
64267282
Email
matthew.chuah@singhealth.com.sg
Facility Name
Singapore General Hospital
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr Swee Du Soon
Phone
62223322
Email
swee.du.soon@singhealth.com.sg
Facility Name
Tan Tock Seng Hospital
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr Alvin Tan Wai Kit
Phone
62566011
Email
alvin_tan@ttsh.com.sg

12. IPD Sharing Statement

Plan to Share IPD
No

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

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