- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04529018
CETO First in Human Trial (CETO)
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Martin Thomas, PhD
- Phone Number: 01223 254 920
- Email: martin.thomas@addenbrookes.nhs.uk
Study Contact Backup
- Name: Russell Senanayake, MRCP, MSc
- Phone Number: 01223 348 739
- Email: russell.senanayake@nhs.net
Study Locations
-
-
Cambridgeshire
-
Cambridge, Cambridgeshire, United Kingdom, CB20QQ
- Recruiting
- Addenbrooke' Hospital
-
Contact:
- Martin Thomas, PhD
- Phone Number: 01223 254 920
- Email: martin.thomas@addenbrookes.nhs.uk
-
Contact:
- Mark Gurnell, FRCP, PhD
- Phone Number: 01223 348739
- Email: mg299@medschl.cam.ac.uk
-
Sub-Investigator:
- Russell Senanayake, MRCP, MSc
-
Sub-Investigator:
- Waiel Bashari, MRCP, MSc
-
Sub-Investigator:
- James MacFarlane, MRCP
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
[18F]CETO is a PET radiotracer used to diagnose and visualise the cause(s) of primary aldosteronism
Other Names:
|
Experimental: 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.
|
[18F]CETO is a PET radiotracer used to diagnose and visualise the cause(s) of primary aldosteronism
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of [18F]CETO administration
Time Frame: 6 months
|
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.
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
[18F]CETO uptake by the the adrenal glands.
Time Frame: 6 months
|
[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.
|
6 months
|
To evaluate uptake in bilateral versus unilateral cases of PA following [18F]CETO administration in up to 6 patients.
Time Frame: 6 months
|
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).
|
6 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Mark Gurnell, PhD, FRCP, University of Cambridge
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CETO-FIH
- 2018-004851-18 (EudraCT Number)
- ISRCTN16159564 (Other Identifier: ISRCTN registry)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Primary Aldosteronism
-
Radboud University Medical CenterCompletedPrimary Aldosteronism | Primary HyperaldosteronismNetherlands
-
Qifu LiWest China Hospital; Tongji Hospital; Second Affiliated Hospital, School of Medicine... and other collaboratorsRecruitingPrimary AldosteronismChina
-
Xiao ChenRecruitingPrimary AldosteronismChina
-
Liverpool University Hospitals NHS Foundation TrustRecruiting
-
The Cleveland ClinicRecruitingPrimary AldosteronismUnited States
-
University of CalgaryCanadian Institutes of Health Research (CIHR); Hypertension CanadaRecruitingPrimary AldosteronismCanada
-
AstraZenecaActive, not recruitingPrimary Aldosteronism | HyperaldosteronismUnited States
-
Chongqing Medical UniversityCompletedPrimary AldosteronismChina
-
Qifu LiThe Affiliated Hospital Of Southwest Medical UniversityCompletedPrimary AldosteronismChina
-
Chongqing Medical UniversityCompletedPrimary AldosteronismChina
Clinical Trials on [18F]CETO
-
Epax Norway ASMøreforsking ASRecruiting
-
Epax Norway ASMøreforsking ASUnknownHealthy VolunteersNorway
-
University of CalgaryNot yet recruiting
-
Genentech, Inc.Completed
-
Adam BrickmanNational Institute on Aging (NIA)Completed
-
Genentech, Inc.Completed
-
Chang Gung Memorial HospitalRecruitingProgressive Supranuclear PalsyTaiwan
-
Five Eleven Pharma, Inc.CompletedParkinson DiseaseUnited States
-
Washington University School of MedicineRecruiting
-
Massachusetts General HospitalActive, not recruiting