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Trial registered on ANZCTR


Registration number
ACTRN12619001738112
Ethics application status
Approved
Date submitted
3/12/2019
Date registered
9/12/2019
Date last updated
17/04/2024
Date data sharing statement initially provided
9/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Identification of aldosterone-producing adenomas using [68Ga]Ga-PentixaFor PET/CT
Scientific title
Identification of aldosterone-producing adrenal adenomas using [68Ga]Ga-PentixaFor PET/CT
Secondary ID [1] 299986 0
Nil known
Universal Trial Number (UTN)
U1111-1244-8647
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary aldosteronism 315457 0
Condition category
Condition code
Metabolic and Endocrine 313756 313756 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intended intervention in this trial is a 68Ga-PentixaFor PET-CT scan, performed in individuals with confirmed primary aldosteronism and an adrenal adenoma, who are planned to undergo adrenal vein sampling (AVS) for subtyping. This nuclear medicine study will be timed to occur within 2-4 weeks of AVS. All participants will undergo both AVS and the PET-CT scan, with the result of the latter being compared to AVS which is the current gold standard for subtyping primary aldosteronism.
There will be no pre-treatment preceding the scan.
The nuclear medicine procedure will require intravenous administration of the tracer, followed by dynamic PET/CT imaging at 10 and 40 mins. The dose of intravenously injected [68Ga]Ga-PentixaFor PET/CT will be calculated based on the patient's weight (1.85 MBq [0.05mCi]/kg).

PET/CT scanning will be performed at 10 minutes and 40 minutes after the injection of the intravenous tracer. The PET/CT image will be evaluated by an experienced nuclear medicine physician who is blinded to the AVS result. The shape and density of adrenal glands will be analyzed.

The 68Ga-PET/CT intervention will be administered by a nuclear medicine physician and on-site technician. Scans will be made from the vertex to upper thighs, with an acquisition time equivalent to 3-5 minutes per step. The complete procedure for the scan will require one visit to the nuclear medicine department.

AVS occurring as part of standard care will be performed by one of two skilled interventional radiologists who routinely perform this procedure for our centre.
Intervention code [1] 316256 0
Diagnosis / Prognosis
Comparator / control treatment
Adrenal vein sampling (AVS) is the standard of care in subtyping of primary aldosteronism to differentiate between unilateral and bilateral aldosterone excess. AVS requires a skilled interventional radiologist, and patient preparation must occur weeks in advance to ensure elimination of interfering medications. During AVS, adrenal and peripheral veins are simultaneously catheterized through a percutaneous femoral vein approach under fluoroscopic guidance. Contrast is administered for catheter guidance and to identify the location of the catheter tip. Blood is aspirated as the catheter is threaded, and labeled samples are then assayed for aldosterone and cortisol concentrations. Serum cortisol measurements are used to confirm successful cannulation of the adrenal vein, and additionally to correct serum aldosterone measurements for dilutional effects. The risks of AVS are bleeding, venous thrombosis, venous rupture, a stroke, allergic reaction to contrast, damage to surrounding anatomical structures, rupture of the adrenal gland, and it is additionally a difficult procedure that at times will need to be repeated.
Control group
Active

Outcomes
Primary outcome [1] 322167 0
Primary outcome:
Subtype as assessed by standardised uptake values (SUV) on 68Ga-PentixaFor PET-CT scanning.
The maximal standardized uptake value (SUVmax) of both adrenals will be measured, including area with or without abnormalities on CT. Average SUVmax of five round spheres with a diameter of 2 cm was selected from the liver as the background. A consensus report will be generated commenting on the location of the lesion and the value of SUVmax.
The concluded subtype will be compared to the outcome of lateralisation by AVS.

Method by which primary outcome of SUV is calculated: Attenuation and decay-corrected images are converted to SUV maps through division by injected activity per patient weight. The maximum SUV values over regions of interest are determined for time 0-1 hour after the injection. Images will be analysed and reported in line with previously published manuscripts:
- Ding J, Zhang Y, Wen J, Zhang H, Wang H, Luo Y, et al. Imaging CXCR4 expression in patients with suspected primary hyperaldosteronism. Eur J Nucl Med Mol Imaging. 2020;47(11):2656-65.
- Heinze B, Fuss CT, Mulatero P, Beuschlein F, Reincke M, Mustafa M, et al. Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma. Hypertension. 2018;71(2):317-25.
Timepoint [1] 322167 0
Patients who are successfully recruited into the study will be planned for a 68Ga-Pentixafor PET-CT scan within 4 weeks of AVS, with an aim to perform both investigations as close to each other as possible. Given the resources and cost associated with manufacturing 68Ga-Pentixafor, the aim is to scan 2 patients at a time. The anticipated schedule of these scans has been determined by availability of staffing, equipment, and production of 68Ga-Pentixafor. Participants will have pre-scan counselling at the nuclear medicine department.
Secondary outcome [1] 377556 0
Nil
Timepoint [1] 377556 0
Nil

Eligibility
Key inclusion criteria
1) Age > 18
2) Confirmed diagnosis of primary aldosteronism
3) Adrenal adenoma seen on CT (any size, either unilateral or bilateral)
4) Planned for lateralisation with AVS (consented for and suitable to undergo AVS)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Pregnancy or breastfeeding
2) Current active malignancy
3) Cortisol excess – morning cortisol > 50 nmol/L after 1mg dexamethasone suppression test
4) Familial hyperaldosteronism
5) Imaging suggestive of phaeochromocytoma or adrenal cortical carcinoma
6) Unable to come off interfering medications (e.g. due to severe hypertension)

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Section not relevant as not a randomised study
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
The pilot study will assess 20 consecutive patients with primary aldosteronism and an adrenal adenoma, who will also undergo AVS.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The SUV from the adrenal tissues (tumour or normal tissue) obtained from the PET scan will be analysed to derive a cut-off ratio (tumour SUV: normal tissue SUV) that maximises the sensitivity and specificity of the test.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
6/02/2023
Actual
8/02/2023
Date of last participant enrolment
Anticipated
31/12/2023
Actual
3/01/2024
Date of last data collection
Anticipated
31/05/2025
Actual
Sample size
Target
35
Accrual to date
Final
34
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 15385 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 28702 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 304447 0
Charities/Societies/Foundations
Name [1] 304447 0
CASS Foundation
Country [1] 304447 0
Australia
Primary sponsor type
Hospital
Name
Monash Health - Department of Endocrinology
Address
246 Clayton Rd, Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 304708 0
None
Name [1] 304708 0
None
Address [1] 304708 0
None
Country [1] 304708 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304879 0
Monash Health Research Support Services
Ethics committee address [1] 304879 0
Ethics committee country [1] 304879 0
Australia
Date submitted for ethics approval [1] 304879 0
16/08/2019
Approval date [1] 304879 0
12/12/2019
Ethics approval number [1] 304879 0
RES-19-0000-828A

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98510 0
Dr Jimmy Shen
Address 98510 0
Department of Endocrinology
Monash Health
246 Clayton Rd, Clayton VIC 3168
Country 98510 0
Australia
Phone 98510 0
+61 3 9594 6666
Fax 98510 0
Email 98510 0
jimmy.shen@hudson.org.au
Contact person for public queries
Name 98511 0
Jun Yang
Address 98511 0
Department of Endocrinology
Monash Health
246 Clayton Rd, Clayton VIC 3168
Country 98511 0
Australia
Phone 98511 0
+61 3 9594 6666
Fax 98511 0
Email 98511 0
Jun.yang@hudson.org.au
Contact person for scientific queries
Name 98512 0
Jun Yang
Address 98512 0
Department of Endocrinology
Monash Health
246 Clayton Rd, Clayton VIC 3168
Country 98512 0
Australia
Phone 98512 0
+61 3 9594 6666
Fax 98512 0
Email 98512 0
Jun.yang@hudson.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The nuclear medicine scans will be individual to each patient and deemed confidential. AVS as part of standard patient care will not be shared as it confidential health information.


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.