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| Name | Class |
|---|---|
| Samsung Medical Center | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AVS + 68Ga-pentixafor PET/CT (+ 11C-metomidate PET/CT) | Experimental | Intervention: Diagnostic Imaging: 68Ga-pentixafor PET/CT With 68Ga-pentixafor PET/CT imaging added to AVS for lateralization Subset only: 11C-metomidate PET/CT (for research use only, not used in treatment decisions) |
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| AVS only | No Intervention | No PET/CT Without 68Ga-pentixafor PET/CT imaging; AVS only (Gold standard) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 68Ga-pentixafor PET/CT | Diagnostic Test | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Biochemical remission rate after adrenalectomy (surgery group only) | 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. | 6 months after adrenalectomy |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical remission rate after adrenalectomy or initiation of medical therapy | 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. | 6 months after treatment (surgery or medication) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Seungho Lee, M.D | Contact | 82-10-8629-9209 | ganymedes10@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Su-jin Kim, M.D, Ph.D | Seoul National University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Samsung Medical Center | Recruiting | Seoul | Gangnam-gu | 06351 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35417953 | Background | Kim JH, Ahn CH, Kim SJ, Lee KE, Kim JW, Yoon HK, Lee YM, Sung TY, Kim SW, Shin CS, Koh JM, Lee SH. Outcome-Based Decision-Making Algorithm for Treating Patients with Primary Aldosteronism. Endocrinol Metab (Seoul). 2022 Apr;37(2):369-382. doi: 10.3803/EnM.2022.1391. Epub 2022 Apr 14. | |
| 37393373 | Background |
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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.
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| Agreement rate between PET/CT imaging and adrenal venous sampling (AVS) | 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. | 6 months after treatment (surgery or medication) |
| Concordance between AVS-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2 | 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. | 6 months after treatment |
| Concordance between PET/CT-based lateralization and immunohistochemical (IHC) expression of CXCR4 and CYP11B2 | 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. | 6 months after treatment |
| Correlation between the AVS-derived lateralization index and the SUVmax ratio on PET/CT | 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 | 6 months after treatment |
| Change in plasma aldosterone concentration/aldosterone-to-renin ratio (ARR) | 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. | Baseline and 6 months after treatment |
| Rate of blood pressure normalization | 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. | 6 months after treatment |
| Change in antihypertensive medication use | 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. | Baseline and 6 months after treatment |
| Change in serum potassium level | 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. | Baseline and 6 months after treatment |
| Frequency and percentage of histologic subtype classification in resected adrenal tissue | 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. | 3 months after adrenalectomy |
| Size of resected adrenal tumors | Size of resected adrenal tumors will be assessed. Tumor diameter will be measured in centimeters based on pathology reports. | 3 months after adrenalectomy |
| Correlation between somatic mutations and PET/CT SUVmax ratio | 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. | 3 months after adrenalecotmy |
| Seoul National University Hospital | Recruiting | Seoul | Jongno-gu | 03080 | South Korea |
|
| Ren X, Cheng G, Wang Z. Advances in the molecular imaging of primary aldosteronism. Ann Nucl Med. 2023 Aug;37(8):433-441. doi: 10.1007/s12149-023-01851-y. Epub 2023 Jul 2. |
| 33055298 | Background | Soinio M, Luukkonen AK, Seppanen M, Kemppainen J, Seppanen J, Pienimaki JP, Leijon H, Vesterinen T, Arola J, Lantto E, Helin S, Tikkanen I, Metso S, Mirtti T, Heiskanen I, Norvio L, Tiikkainen M, Tikkanen T, Sane T, Valimaki M, Gomez-Sanchez CE, Porsti I, Nuutila P, Nevalainen PI, Matikainen N. Functional imaging with 11C-metomidate PET for subtype diagnosis in primary aldosteronism. Eur J Endocrinol. 2020 Dec;183(6):539-550. doi: 10.1530/EJE-20-0532. |
| 22112805 | Background | 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. |
| 29279316 | Background | Heinze B, Fuss CT, Mulatero P, Beuschlein F, Reincke M, Mustafa M, Schirbel A, Deutschbein T, Williams TA, Rhayem Y, Quinkler M, Rayes N, Monticone S, Wild V, Gomez-Sanchez CE, Reis AC, Petersenn S, Wester HJ, Kropf S, Fassnacht M, Lang K, Herrmann K, Buck AK, Bluemel C, Hahner S. Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma. Hypertension. 2018 Feb;71(2):317-325. doi: 10.1161/HYPERTENSIONAHA.117.09975. Epub 2017 Dec 26. |
| 26975712 | Background | Umakoshi H, Naruse M, Wada N, Ichijo T, Kamemura K, Matsuda Y, Fujii Y, Kai T, Fukuoka T, Sakamoto R, Ogo A, Suzuki T, Nanba K, Tsuiki M; WAVES-J Study Group. Adrenal Venous Sampling in Patients With Positive Screening but Negative Confirmatory Testing for Primary Aldosteronism. Hypertension. 2016 May;67(5):1014-9. doi: 10.1161/HYPERTENSIONAHA.115.06607. Epub 2016 Mar 14. |
| 24218436 | Background | Rossi GP, Auchus RJ, Brown M, Lenders JW, Naruse M, Plouin PF, Satoh F, Young WF Jr. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension. 2014 Jan;63(1):151-60. doi: 10.1161/HYPERTENSIONAHA.113.02097. Epub 2013 Nov 11. |
| 22135219 | Background | Hannemann A, Wallaschofski H. Prevalence of primary aldosteronism in patient's cohorts and in population-based studies--a review of the current literature. Horm Metab Res. 2012 Mar;44(3):157-62. doi: 10.1055/s-0031-1295438. Epub 2011 Dec 1. |
| 17161262 | Background | Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, Ganzaroli C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Mattarello MJ, Moretti A, Palumbo G, Parenti G, Porteri E, Semplicini A, Rizzoni D, Rossi E, Boscaro M, Pessina AC, Mantero F; PAPY Study Investigators. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006 Dec 5;48(11):2293-300. doi: 10.1016/j.jacc.2006.07.059. Epub 2006 Nov 13. |
| 26934393 | Background | Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10.1210/jc.2015-4061. Epub 2016 Mar 2. |
| ID | Term |
|---|---|
| D006929 | Hyperaldosteronism |
| D018246 | Adrenocortical Adenoma |
| ID | Term |
|---|---|
| D000308 | Adrenocortical Hyperfunction |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D000306 | Adrenal Cortex Neoplasms |
| D000310 | Adrenal Gland Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D000303 | Adrenal Cortex Diseases |
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