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CETO First in Human Trial (CETO)

Primary Purpose

Primary Aldosteronism

Status

Unknown status

Phase

Not Applicable

Locations

United Kingdom

Study Type

Interventional

Intervention

[18F]CETO

About this trial

This is an interventional diagnostic trial for Primary Aldosteronism focused on measuring Adrenal, Conn's, Endocrine, Aldosterone

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

Addenbrooke' HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Healthy Volunteers

Patients with primary aldosteronism

Arm 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.

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.

Outcomes

Primary Outcome Measures

Safety of [18F]CETO administration

The primary outcome measure is the overall safety of [18F]CETO. This will be assessed according to the frequency of adverse events, serious adverse events, clinically significant changes in vital signs, ECG and laboratory parameters.

Secondary Outcome Measures

[18F]CETO uptake by the the adrenal glands.

[18F]CETO uptake by the adrenal glands will be assessed by measurement of Standardized Uptake Values (SUV) over the left and right adrenal glands. All assessments will be performed by a dedicated blinded reviewer.

To evaluate uptake in bilateral versus unilateral cases of PA following [18F]CETO administration in up to 6 patients.

Evaluation of adrenal uptake of [18F]CETO in bilateral versus unilateral cases of PA will be performed by comparing SUV values of both adrenal glands in three patients with each subtype of PA (using a dedicated blinded reviewer).

Full Information

NCT ID

NCT04529018

First Posted

August 13, 2020

Last Updated

August 24, 2020

Sponsor

University of Cambridge

Collaborators

Cambridge University Hospitals NHS Foundation Trust

1. Study Identification

Unique Protocol Identification Number

NCT04529018

Brief Title

CETO First in Human Trial

Acronym

CETO

Official Title

A Phase 1 Clinical Trial Evaluating the Safety and Efficacy of up to Two Administrations of the Adrenal PET Tracer [18F]CETO in Healthy Volunteers and Patients With Primary Aldosteronism

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Unknown status

Study Start Date

August 3, 2020 (Actual)

Primary Completion Date

November 30, 2020 (Anticipated)

Study Completion Date

November 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Cambridge

Collaborators

Cambridge University Hospitals NHS Foundation Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Aldosteronism

Keywords

Adrenal, Conn's, Endocrine, Aldosterone

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Phase I single-centre, open-label, micro-dosing study

Masking

Outcomes Assessor

Masking Description

Scans will be assessed by two independent nuclear medicine physicians, who will be blinded to patient identifiable data when analysing PET-CT scans.

Allocation

Non-Randomized

Enrollment

11 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Healthy Volunteers

Arm Type

Experimental

Arm 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.

Arm Title

Patients with primary aldosteronism

Arm Type

Experimental

Arm Description

Intervention Type

Combination Product

Intervention Name(s)

[18F]CETO

Other Intervention Name(s)

CETO

Intervention Description

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

Primary Outcome Measure Information:

Title

Safety of [18F]CETO administration

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

[18F]CETO uptake by the the adrenal glands.

Description

Time Frame

6 months

Title

To evaluate uptake in bilateral versus unilateral cases of PA following [18F]CETO administration in up to 6 patients.

Description

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility 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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Martin Thomas, PhD

Phone

01223 254 920

martin.thomas@addenbrookes.nhs.uk

First Name & Middle Initial & Last Name or Official Title & Degree

Russell Senanayake, MRCP, MSc

Phone

01223 348 739

russell.senanayake@nhs.net

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark Gurnell, PhD, FRCP

Organizational Affiliation

University of Cambridge

Official's Role

Principal Investigator

Facility Information:

Facility Name

Addenbrooke' Hospital

City

Cambridge

State/Province

Cambridgeshire

ZIP/Postal Code

CB20QQ

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mark Gurnell, FRCP, PhD

Phone

01223 348739

mg299@medschl.cam.ac.uk

First Name & Middle Initial & Last Name & Degree

Martin Thomas, PhD

Phone

01223 254 920

martin.thomas@addenbrookes.nhs.uk

First Name & Middle Initial & Last Name & Degree

Russell Senanayake, MRCP, MSc

First Name & Middle Initial & Last Name & Degree

Waiel Bashari, MRCP, MSc

First Name & Middle Initial & Last Name & Degree

James MacFarlane, MRCP

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

22112805

Citation

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.

Results Reference

background

PubMed Identifier

18397978

Citation

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.

Results Reference

background

PubMed Identifier

10688111

Citation

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.

Results Reference

background

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