Subtyping Primary Aldosteronism with Para-chloro-2-[18F]fluoroethyl-etomidate (SPACE)

Para-chloro-2-[18F]fluoroethyl-etomidate ([18F]CETO) As a New PET-tracer for Subtyping in Patients with Primary Aldosteronism - a Pilot Study

The goal of this clinical trial is to investigate the uptake characteristics of [18F]CETO in adrenal tissue in patients with two different subtypes of primary aldosteronism. The main questions it aims to answer are:

• What are the uptake characteristics of [18F]CETO in adrenal tissue in patients with primary aldosteronism?
• What is the concordance between the adrenal vein sampling and the [18F]CETO PET/CT scan results?
• What is the effect of adrenal perfusion on [18F]CETO uptake in the adrenal glands?

Researchers will compare the results of the adrenal vein sampling to a [18F]CETO PET/CT scan to see if the PET/CT can accurately identify the subtypes of primary aldosteronism. Participants will:

• Take dexamethasone three days prior to the scan
• Undergo a [18F]CETO PET/CT
• Report burden of pre-treatment and PET/CT scan

Study Overview

• Status: Recruiting
• Conditions: Primary Aldosteronism
• Intervention / Treatment: Drug: [18F]CETO tracer; Drug: Dexamethasone oral; Procedure: Adrenal vein sampling

Detailed Description

Rationale Primary aldosteronism (PA) is a relatively frequent and clinically relevant secondary cause of hypertension. PA is usually caused by either an aldosterone producing adrenal adenoma (APA) or bilateral adrenal hyperplasia (BAH). Differentiation between these two subtypes is important as it determines the treatment of choice, i.e., unilateral adrenalectomy in case of APA and medical treatment with a mineralocorticoid receptor antagonist in case of BAH. Adrenal vein sampling (AVS) is considered the optimal diagnostic test for this subtyping and is recommended in most patients with PA who are a candidate for surgery. AVS, however, is an invasive and time-consuming procedure with limited availability due to the special expertise required. Additional disadvantages are the risk of procedure related complications and the relative high costs. Thus, there is an unmet need for a non-invasive, faster, more patient friendly and less expensive diagnostic test which can distinguish between the two main subtypes of PA. PET/CT with para-chloro-2-[18F]fluoroethyl-etomidate ([18F]CETO) has a high specificity for the steroidogenic enzymes CYP11B1 and CYP11B2, present in the adrenal cortex, and has more favourable tracer characteristics compared to [11C]metomidate. Results obtained with this novel tracer seem promising, but its potential value in the subtyping of PA needs to be further established. Our hypothesis is that [18F]CETO PET/CT is selectively taken up by aldosterone producing adrenal tissue.

Objective The main objective is to investigate the uptake characteristics of [18F]CETO in adrenal tissue in patients with either APA or BAH. The secondary objective is to evaluate the concordance between the results of adrenal vein sampling and the results of the [18F]CETO scan. In addition, the effect of tissue perfusion on the [18F]CETO uptake by means of a 15O water scan is studied.

Main trial endpoints The main trial endpoint is the investigation of [18F]CETO uptake by adrenal gland tissue in patients with either APA or BAH. Descriptive statistics will be used to explore uptake characteristics.

Secondary trial endpoints The secondary trial end points are i) the concordance between the results of adrenal vein sampling and ii) the relationship between adrenal perfusion and [18F]CETO uptake Trial design Prospective, single-center, diagnostic, observational pilot study. The expected duration of this study is 2 years.

Trial population Adult patients > 18 years of age with biochemically confirmed PA who underwent a successful AVS (n=12) are eligible for inclusion. Main exclusion criteria are diabetes mellitus, serious comorbidity precluding surgery and use of specific medications.

Interventions Participating patients have been subjected to the routine diagnostic work-up for PA as recommended by the guideline of the European Society of Hypertension (2020), including hormonal evaluation before and after a salt-loading protocol, CT or MRI of the adrenal glands and AVS. Three days prior to the PET/CT scans, patients receive pretreatment with dexamethasone in order to enhance tracer specificity. Each participant will be subjected to one additional hospital visit for the investigational diagnostic PET-CT procedure with the administration of [18F]CETO, which is directly preceded by a 15O water scan.

Ethical considerations relating to the clinical trial including the expected benefit to the individual subject or group of patients represented by the trial subjects as well as the nature and extent of burden and risks.

No adverse effects following [18F]CETO and 15O water injection have been reported in the literature. Pretreatment with dexamethasone is recommended for the [18F]CETO PET/CT and could result in mild reversible side effects (hyperglycemia, mood changes, sleep disturbance), which will be monitored by means of a non-invasive questionnaire. As this is a diagnostic pilot study, participating patients will not benefit directly from this investigational diagnostic procedure. However, patients contribute to gathering information on the application of [18F]CETO PET/CT, potentially reducing the need for AVS in future patients.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: dr. M.N. Kerstens; Phone Number: +31 0503613518; Email: m.n.kerstens@umcg.nl
• Study Contact Backup: Name: Merit Schaafsma, MD-PhD candidate; Phone Number: +31503610972; Email: m.schaafsma@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • University Medical Center Groningen
    • Contact: Dr. M.N. Kerstens; Phone Number: +31503613518; Email: m.n.kerstens@umcg.nl
    • Contact: Dr. M.N. Kerstens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• above 18 years
• Biochemically established diagnosis of PA*
• Completion of standard diagnostic work-up of PA*
• Able to follow and understand instructions to participate in the study
• Able to give written informed consent.

Exclusion Criteria:

• diabetes mellitus (i.e., HbA1c above 42 mmol/mol, and/or fasting plasma glucose > 7.0 mol/l or non-fasting plasma glucose above 11.1 mmol/L )
• serious comorbidities precluding surgery
• severe claustrophobia
• pregnancy/breastfeeding or unable/unwilling to take adequate contraceptives (female only)
• concurrent active infections (e.g., viral, fungal or parasite infections)**
• problematic venous access
• unable/unwilling to take dexamethasone prior to [18F]CETO scanning
• inability to temporary stop medication affecting aldosterone secretion
• use of ketoconazole, metyrapone or cytostatic drugs during previous 6 months***
• long-term use of prednisolone and/or dexamethasone.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aldosterone producing adenoma; Patients diagnosed with an aldosterone producing adenoma	Drug: [18F]CETO tracer; PET/CT with para-chloro-2-[18F]fluoroethyl-etomidate ([18F]CETO) has a high specificity for the steroidogenic enzymes CYP11B1 and CYP11B2, present in the adrenal cortex, and has more favourable tracer characteristics compared to [11C]metomidate. Results obtained with this novel tracer seem promising, but its potential value in the subtyping of PA needs to be further established.; Other Names: Para-chloro-2-[18F]fluoroethyl-etomidate ([18F]CETO); Drug: Dexamethasone oral; Pre-treatment of dexamethasone prior to 18F CETO PET/CT scan; Procedure: Adrenal vein sampling; Adrenl vein sampling; Other Names: AVS
Active Comparator: Bilateral adrenal hyperplasia; Patients diagnosed with bilateral adrenal hyperplasia	Drug: [18F]CETO tracer; PET/CT with para-chloro-2-[18F]fluoroethyl-etomidate ([18F]CETO) has a high specificity for the steroidogenic enzymes CYP11B1 and CYP11B2, present in the adrenal cortex, and has more favourable tracer characteristics compared to [11C]metomidate. Results obtained with this novel tracer seem promising, but its potential value in the subtyping of PA needs to be further established.; Other Names: Para-chloro-2-[18F]fluoroethyl-etomidate ([18F]CETO); Drug: Dexamethasone oral; Pre-treatment of dexamethasone prior to 18F CETO PET/CT scan; Procedure: Adrenal vein sampling; Adrenl vein sampling; Other Names: AVS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uptake characteristics [18F]CETO	Visual description of uptake characteristics of [18F]CETO uptake in adrenal tissue in patients with APA or BAH.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concordance adrenal vein sampling and [18F]CETO PET/CT scan	Concordance between the adrenal vein sampling and the results of the [18F]CETO scan will be expressed in percentages.	2 years

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Dr. M.N. Kerstens, Department of Internal Medicine - Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

Publications and helpful links

General Publications

• Silins I, Sundin A, Lubberink M, O'Sullivan L, Gurnell M, Aigbirhio F, Brown M, Wall A, Akerstrom T, Roslin S, Hellman P, Antoni G. First-in-human evaluation of [18F]CETO: a novel tracer for adrenocortical tumours. Eur J Nucl Med Mol Imaging. 2023 Jan;50(2):398-409. doi: 10.1007/s00259-022-05957-9. Epub 2022 Sep 8.
• Silins I, Sundin A, Nordeman P, Jahan M, Estrada S, Monazzam A, Lubberink M, Aigbirhio F, Hellman P, Antoni G. Para-chloro-2-[18F]fluoroethyl-etomidate: A promising new PET radiotracer for adrenocortical imaging. Int J Med Sci. 2021 Mar 21;18(10):2187-2196. doi: 10.7150/ijms.51206. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: September 19, 2024
• First Submitted That Met QC Criteria: September 24, 2024
• First Posted (Actual): September 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 22, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Primary aldosteronism; PET/CT scan; Bilateral adrenal hyperplasia; Adrenal vein sampling; [18F]CETO; Aldosteron producing Adenoma
• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenocortical Hyperfunction; Hyperaldosteronism; Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anesthetics; Central Nervous System Depressants; Hypnotics and Sedatives; Anesthetics, Intravenous; Anesthetics, General; Dexamethasone; Etomidate
• Other Study ID Numbers: SPACE 2024/176; 2023-508254-26-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD sharing plan has been described in the data management plan.
• IPD Sharing Time Frame: After end of study.
• IPD Sharing Access Criteria: Described in the data management plan
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No