CETO First in Human Trial

NCT ID: NCT04529018

Last Updated: 2020-08-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-03
• Study Completion Date: 2020-11-30

Brief Summary

The study is a Phase 1, single-centre, open label, micro-dosing study. The aim is to investigate an innovative new tracer, [18F]CETO, as a potential alternative to adrenal vein sampling for the lateralisation of primary aldosteronism (PA).

Detailed Description

At least one-quarter of the UK adult population has hypertension, a major risk factor for heart attacks and stroke. Primary aldosteronism (PA), a treatable form of hypertension, accounts for 5-10% of all cases, and 20-25% of difficult to control hypertension. It is challenging to determine whether one adrenal gland is the source of PA (which is potentially curable with surgery) or both glands (which would require long-term drug treatment). Existing lateralising procedures (i.e. investigations to distinguish one from two gland involvement e.g. CT or MRI scan) have significant limitations. Accordingly, most patients must undergo an invasive procedure called adrenal vein sampling (AVS) in which small catheters are placed in each adrenal vein. However, this is time-consuming, technically demanding, and fails in 20-50% of cases. To address this, researchers have adopted a novel approach using PET-CT as an alternative to AVS. Currently, this uses a tracer called metomidate labelled with carbon-11 (11C MTO), which is taken up preferentially by the adrenal gland, and in particular by adrenal tumours causing PA. However, its utility is limited by a short half-life, which means the scan can only be performed in centres with a cyclotron facility (currently less than 10 NHS sites). The aim of this study is to investigate the safety of a new tracer with a longer half-life, [18F]CETO, that could be made available for use in many more centres.

The trial objectives are outlined below:

Primary Objective

To evaluate the safety of up to two administrations of [18F]CETO in up to 6 patients with primary aldosteronism and 5 healthy volunteers.

Secondary Objective

• Assess [18F]CETO uptake by the adrenal glands
• Evaluate uptake in bilateral vs unilateral cases of PA following [18F]CETO administration in up to 6 patients.

Conditions

Primary Aldosteronism

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

Healthy Volunteers

A group of 5 healthy volunteers will be tested with the PET radiotracer \[18F\]CETO to assess safety of tracer administration, and evaluate uptake by the normal adrenal glands.

Group Type: EXPERIMENTAL

[18F]CETO

Intervention Type: COMBINATION_PRODUCT

\[18F\]CETO is a PET radiotracer used to diagnose and visualise the cause(s) of primary aldosteronism

Patients with primary aldosteronism

A group of 6 patients with Primary Aldosteronism (3 with unilateral and 3 with bilateral disease) will be tested with up to two administrations of the PET radiotracer \[18F\]CETO, to assess safety of tracer administration, evaluate the ability of \[18F\]CETO to distinguish between unilateral and bilateral cases of PA, and determine the effect of Dexamethasone in improving the quality of PET-CT images acquired following administration.

Group Type: EXPERIMENTAL

[18F]CETO

Intervention Type: COMBINATION_PRODUCT

\[18F\]CETO is a PET radiotracer used to diagnose and visualise the cause(s) of primary aldosteronism

Interventions

[18F]CETO

\[18F\]CETO is a PET radiotracer used to diagnose and visualise the cause(s) of primary aldosteronism

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

CETO

Eligibility Criteria

Exclusion Criteria

All participants:

• allergy to radiographic contrast agents
• allergy or contraindication to synacthen
• pregnancy, breastfeeding, or the intention to become pregnant during the 6 months following trial participation
• positive pregnancy test at the screening or baseline visits
• assessed by the investigator as being unable or unwilling to comply with the requirements of the study protocol.
• receipt of another IMP as part of a CTIMP
• prior radiation exposure as part of previous research studies
• recreational drug use, or substance/alcohol dependency
• clinically abnormal screening blood tests.

• women of child-bearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile)
• exposure to radiation during their work
• received more than 10 mSv of radioactivity in the past 12 months
• any subject with a history of adrenal disease or who, at the screening visit, reports symptoms, or exhibits physical signs, that could be consistent with previously unsuspected adrenal disease

• allergy or contraindication to dexamethasone treatment (or lactose intolerant)

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: collaborator

University of Cambridge

OTHER

Sponsor Role: lead

Responsible Party

Professor Mark Gurnell

Professor in Clinical Endocrinology and Honorary Consultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Gurnell, PhD, FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Cambridge

Locations

Addenbrooke' Hospital

Cambridge, Cambridgeshire, United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Martin Thomas, PhD

Role: CONTACT

martin.thomas@addenbrookes.nhs.uk

01223 254 920

Russell Senanayake, MRCP, MSc

Role: CONTACT

russell.senanayake@nhs.net

01223 348 739

Facility Contacts

Mark Gurnell, FRCP, PhD

Role: primary

mg299@medschl.cam.ac.uk

01223 348739

Martin Thomas, PhD

Role: backup

martin.thomas@addenbrookes.nhs.uk

01223 254 920

References

Burton TJ, Mackenzie IS, Balan K, Koo B, Bird N, Soloviev DV, Azizan EA, Aigbirhio F, Gurnell M, Brown MJ. Evaluation of the sensitivity and specificity of (11)C-metomidate positron emission tomography (PET)-CT for lateralizing aldosterone secretion by Conn's adenomas. J Clin Endocrinol Metab. 2012 Jan;97(1):100-9. doi: 10.1210/jc.2011-1537. Epub 2011 Nov 23.

Reference Type: BACKGROUND

PMID: 22112805 (View on PubMed)

Hahner S, Stuermer A, Kreissl M, Reiners C, Fassnacht M, Haenscheid H, Beuschlein F, Zink M, Lang K, Allolio B, Schirbel A. [123 I]Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes. J Clin Endocrinol Metab. 2008 Jun;93(6):2358-65. doi: 10.1210/jc.2008-0050. Epub 2008 Apr 8.

Reference Type: BACKGROUND

PMID: 18397978 (View on PubMed)

Bergstrom M, Juhlin C, Bonasera TA, Sundin A, Rastad J, Akerstrom G, Langstrom B. PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer 11C-metomidate. J Nucl Med. 2000 Feb;41(2):275-82.

Reference Type: BACKGROUND

PMID: 10688111 (View on PubMed)

Other Identifiers

2018-004851-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN16159564

Identifier Type: OTHER

Identifier Source: secondary_id

CETO-FIH

Identifier Type: -

Identifier Source: org_study_id