CETO First in Human Trial

University of Cambridge

Status: Unknown

Conditions: Primary Aldosteronism

Treatments: Combination Product: [18F]CETO

Study type: Interventional

Funder types: Other

Identifiers

NCT04529018

2018-004851-18 (EudraCT Number)

ISRCTN16159564 (Other Identifier)

CETO-FIH

Details and patient eligibility

About

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).

Full 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.

Enrollment: 11 estimated patients

Sex: All

Ages: 40+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Healthy Volunteers

To be included in the trial the participant must:

• give written informed consent
• be aged 50 years or over
• have no underlying medical conditions
• be able to lie down for at least 2 hours and not be claustrophobic

In addition, all female participants must be:

• post-menopausal (no menses for 12 months, without an alternative medical cause)

Patients

To be included in the trial the patient must:

• give written informed consent
• be aged 40 years or over
• be able to lie down for at least 2 hours and not be claustrophobic

fulfil the following criteria:

• have a confirmed diagnosis of PA as per Endocrine Society guidelines
• At least one paired measurement of plasma renin and aldosterone, measured off Spironolactone/Eplerenone within past 12 months, showing ARR above local threshold value.
• One of the following two criteria:
• Plasma aldosterone>190pmol/L following saline infusion.
• Spontaneous hypokalaemia, suppressed plasma renin and plasma aldosterone>550pmol/L.
• have undergone successful lateralisation of the cause of PA to one or both adrenal glands by adrenal vein sampling (AVS).
• be willing to have two scans

In addition, all female patients must have a negative (blood) pregnancy test at the screening visit.

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.

Additional exclusion criteria for healthy volunteers:

• 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

Additional exclusion criteria for patients:

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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11 participants in 2 patient groups

Healthy Volunteers

Experimental group

Description:

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.

Treatment:

Combination Product: [18F]CETO

Patients with primary aldosteronism

Experimental group

Description:

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.

Treatment:

Combination Product: [18F]CETO