Adrenalectomy, Aldosterone-Producing Adenoma, Idiopathic Hyperaldosteronism, Primary Aldosteronism, Secondary Hypertension
Conditions
Keywords
Primary aldosteronism, Gallium-68 pentixafor, 11C-metomidate, PET/CT, adrenal venous sampling, PASO, PAMO, Adrenalectomy
Brief summary
This study is a randomized controlled trial to assess the clinical utility of gallium-68 pentixafor PET/CT in the management of primary aldosteronism (PA). We aim to evaluate whether the addition of 68Ga-pentixafor PET/CT to standard adrenal venous sampling (AVS) improves surgical outcomes in patients with unilateral PA.
Detailed description
Primary aldosteronism (PA) is a common cause of secondary hypertension. Accurate subtype classification (unilateral vs. bilateral) is essential to determine whether patients should receive adrenalectomy or medical therapy. AVS is the current gold standard but has limitations, including its invasiveness, technical difficulty, and risk of failure. Recently, non-invasive imaging techniques such as 68Ga-pentixafor PET/CT and 11C-metomidate PET/CT have emerged as promising alternatives for subtype classification. These PET-based methods target molecular markers (e.g., CXCR4, CYP11B2) and show moderate to high concordance rates with AVS (66.7%-90% for pentixafor). However, there is insufficient prospective evidence on whether these modalities can improve treatment outcomes. This randomized controlled trial aims to assess whether adding 68Ga-pentixafor PET/CT to standard AVS improves surgical outcomes in patients with unilateral PA. Participants are randomized 1:1 to undergo either AVS alone or AVS plus 68Ga-pentixafor PET/CT. Additionally, 11C-metomidate PET/CT is performed in the intervention arm purely for research purposes and will not influence treatment decisions. By improving the precision of subtype classification, this study aims to improve patient selection for adrenalectomy, and ultimately enhance clinical outcomes in primary aldosteronism.
Interventions
DIAGNOSTIC_TEST68Ga-pentixafor PET/CT
Diagnostic PET/CT imaging using gallium-68 labeled pentixafor to assess adrenal CXCR4 expression in patients with primary aldosteronism. The imaging is performed prior to treatment allocation and used to assist lateralization of aldosterone production when combined with adrenal venous sampling (AVS).
Sponsors
Samsung Medical Center
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Masking description
The nuclear medicine physician interpreting PET/CT scans is masked to AVS results. However, participants and treating clinicians are not blinded due to the nature of the intervention.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥19 years * Diagnosed with PA per 2016 Endocrine Society guidelines * Underwent adrenal CT * Signed informed consent
Exclusion criteria
* Women who are pregnant, breastfeeding, or may become pregnant * Individuals who refuse to undergo surgery * Individuals for whom 68Ga-Pentixafor PET/CT, 11C-Metomidate PET/CT, or adrenal venous sampling (AVS) is not feasible or is refused due to underlying conditions * Individuals who refuse or experience adverse effects from dexamethasone premedication required for 11C-Metomidate PET/CT * Individuals with a history of abdominal open surgery or retroperitoneal surgery on the same side as the planned adrenalectomy * Any individual deemed unsuitable for the study at the discretion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical remission rate after adrenalectomy (surgery group only) | 6 months after adrenalectomy | Number of participants achieving biochemical success as defined by PASO criteria will be assessed. Biochemical success is defined as normalization or improvement in aldosterone-to-renin ratio (ARR) and correction of hypokalemia without potassium supplementation in patients with unilateral primary aldosteronism who underwent adrenalectomy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Agreement rate between PET/CT imaging and adrenal venous sampling (AVS) | 6 months after treatment (surgery or medication) | Agreement rate between 68Ga-pentixafor PET/CT (+11C-metomidate PET/CT for subgroup) and adrenal venous sampling (AVS) will be assessed. Diagnostic agreement will be evaluated based on lateralization patterns from PET/CT and AVS using predefined laterality thresholds. |
| Concordance between AVS-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2 | 6 months after treatment | Concordance between AVS-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2 will be assessed. IHC positivity for CXCR4 and CYP11B2 will be recorded as presence or absence in each adrenal lesion. Concordance will be evaluated by comparing lateralization results from AVS with the presence or absence of expression. |
| Concordance between PET/CT-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2 | 6 months after treatment | Concordance between PET/CT-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2 will be assessed. IHC positivity for CXCR4 and CYP11B2 will be recorded as presence or absence in each adrenal lesion. Concordance will be evaluated by comparing PET/CT-based lateralization with the presence or absence of expression in the corresponding adrenal tissue. |
| Correlation between the AVS-derived lateralization index and the SUVmax ratio on PET/CT | 6 months after treatment | The correlation between the AVS-derived lateralization index and the SUVmax ratio on PET/CT will be evaluated. SUVmax ratios will be quantitatively compared with AVS findings, including the lateralization index, as well as tumor size and the side of dominant hormone secretion |
| Change in plasma aldosterone concentration/aldosterone-to-renin ratio (ARR) | Baseline and 6 months after treatment | Change from baseline in plasma aldosterone concentration and ARR will be assessed. Plasma aldosterone and ARR will be measured at baseline and 6 months post-treatment to evaluate endocrine improvement. |
| Clinical remission rate after adrenalectomy or initiation of medical therapy | 6 months after treatment (surgery or medication) | Number of participants achieving clinical success according to PASO (surgical group) or PAMO (medical group) criteria will be assessed. Clinical success includes normalization of blood pressure and reduction in number or dose of antihypertensive medications after surgery or medical therapy. |
| Change in antihypertensive medication use | Baseline and 6 months after treatment | Change in number and dose of antihypertensive medications from baseline will be assessed. Total daily defined dose and number of medications will be compared between baseline and 6 months after treatment. |
| Change in serum potassium level | Baseline and 6 months after treatment | Change in serum potassium concentration from baseline will be assessed. Serum potassium levels at baseline and 6 months post-treatment will be compared to evaluate metabolic improvement. |
| Frequency and percentage of histologic subtype classification in resected adrenal tissue | 3 months after adrenalectomy | Frequency and percentage of histologic subtype classification in resected adrenal tissue will be assessed. Resected adrenal tissues will be classified according to histologic subtypes, and the distribution of each subtype will be recorded. |
| Size of resected adrenal tumors | 3 months after adrenalectomy | Size of resected adrenal tumors will be assessed. Tumor diameter will be measured in centimeters based on pathology reports. |
| Correlation between somatic mutations and PET/CT SUVmax ratio | 3 months after adrenalecotmy | The correlation between somatic mutations and PET/CT SUVmax ratios of adrenal tumors will be evaluated. Mutation profiles (e.g., KCNJ5, CACNA1D, etc.) will be analyzed in relation to SUVmax measurements obtained from PET/CT imaging. |
| Rate of blood pressure normalization | 6 months after treatment | Proportion of participants with blood pressure below 140/90 mmHg without escalation of antihypertensive medications will be assessed. Participants achieving target blood pressure without medication escalation will be recorded. |
Countries
South Korea
Contacts
Primary ContactSeungho Lee, M.D
Outcome results
None listed