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Trial registered on ANZCTR


Registration number
ACTRN12619001738112p
Ethics application status
Submitted, not yet approved
Date submitted
3/12/2019
Date registered
9/12/2019
Date last updated
9/12/2019
Date data sharing statement initially provided
9/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Novel 124I-iodometomidate PET/CT in subtyping of primary aldosteronism
Scientific title
The novel use of 124I-iodometomidate PET-CT in subtyping primary aldosteronism - a prospective pilot study evaluating the utility of this non-invasive technique in lateralisation of primary aldosteronism as compared to adrenal vein sampling
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 124I-iodometomidate PET-CT scan, performed in individuals with confirmed primary aldosteronism and are planned to undergo adrenal vein sampling for subtyping. This nuclear medicine study will be timed to occur as soon as possible after completion of AVS, at the latest three weeks after AVS. All recruited participants will require drug therapy preceding the scan, specifically oral dexamethasone 2mg daily in divided doses for three days before scanning and oral Lugol's 1% iodine solution for two days in total starting one day before the scan. Participants will be given written instructions regarding pre-scan drug therapy and will be given a checklist to tick off when they have taken the medication. They will be asked to bring this checklist in with them to be verified prior to the scan. Contact details will be provided should the participants experience any issues with the pre-scan therapy that affect (or preclude) successful pre-medication.
The nuclear medicine procedure will require intravenous administration of 3mCi (111MBq) of 124I-Iodometomidate, followed by dynamic PET/CT imaging over the adrenal bed from T0 to T0+1hour followed by whole body PET/CT imaging at T0 + 2h, 24 & 48hrs using a Siemens Biograph mCT Flow or Siemens Biograph Truepoint PET/CT scanners with True V (extended field of view) (Monash Health) and combined with low dose CT for attenuation correction and anatomical localisation. The intervention will be administered by a nuclear medicine physician, with the support of on-site technicians. 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 three visits to the nuclear medicine department on consecutive days, the first visit lasting two hours, the second and third lasting less than an hour each.
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 124I-iodometomidate PET-CT scanning
- SUV will be individually analysed by an independent single radiologist
- 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 1-2, 24 and 48 hours after the injection. Images are analysed and reported in line with previously published standards (Burton TJ, Mackenzie IS, Balan K et al. 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).
Timepoint [1] 322167 0
Patients who are successfully recruited into the study will be planned for a 124I-iodometomidate PET-CT scan as soon as possible after completion of AVS. Given the significant cost associated with 124I-iodometomidate production per episode, there will be cost benefit gained by bundling up to 4-5 patients per batch of metomidate production. The scheduling of which will be determined by the timing of AVS and availability of the PET tracer and PET/CT imaging. Participants will be scheduled for pre-scan counselling appointment at the nuclear medicine department prior to the study.
The nuclear medicine scan will be performed as soon as possible after AVS (within three weeks) and the scan will be interpreted within 1-5 days.
Secondary outcome [1] 377556 0
Nil
Timepoint [1] 377556 0
Nil

Eligibility
Key inclusion criteria
1) Age > 18
2) Confirmed diagnosis of PA
3) Have undergone lateralisation with AVS
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Diabetes mellitus, thyroid dysfunction or any psychiatric illnesses (unsuitable for dexamethasone pre-treatment)
2) Difficult-to-manage hypertension requiring treatment with spironolactone
3) Other causes of secondary hypertension
4) Long-term corticosteroid therapy
5) Renal failure with eGFR <30

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled 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)
The pilot study will assess 10 consecutive patients with bilateral adrenal hyperplasia and 10 with APA after subtyping using AVS, which will act as the control benchmark.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
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
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Self funded/Unfunded
Name [1] 304447 0
Address [1] 304447 0
Country [1] 304447 0
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
Submitted, not yet approved
Ethics committee name [1] 304879 0
Monash Health Research Support Services
Ethics committee address [1] 304879 0
Level 2, i Block,
Monash Medical Centre
246 Clayton Road
CLAYTON VIC 3168
Ethics committee country [1] 304879 0
Australia
Date submitted for ethics approval [1] 304879 0
10/12/2019
Approval date [1] 304879 0
Ethics approval number [1] 304879 0

Summary
Brief summary
Differentiation between bilateral and unilateral (aldosterone-producing adenoma, APA) causes of primary aldosteronism (PA) relies on CT imaging of the adrenal glands and adrenal vein sampling (AVS), the latter of which is the current gold standard. CT imaging is limited by a high rate of adrenal incidentalomas, which can lead to dilemmas in management and pursuance of extensive investigations. AVS is operator dependent, labour intensive, expensive and invasive, also posing the risk of a failed or inconclusive study. We conduct this pilot prospective study in adults with confirmed PA with the objective of evaluating the efficacy of 124I-iodometomidate PET-CT in subtyping primary aldosteronism, compared to AVS as the gold standard.
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
Dr 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
Dr 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 other documents available
Summary results
No Results