Tirzepatide Following Adrenalectomy in Mild Autonomous Cortisol Secretion
28 juli 2026 bijgewerkt door: Alaa Sada
A Randomized Clinical Trial of Tirzepatide Following Adrenalectomy in Mild Autonomous Cortisol Secretion
Mild Autonomous Cortisol Secretion (MACS) is a condition in which an adrenal gland produces excess cortisol and is associated with high blood pressure, diabetes, and weight gain. Surgical removal of the adrenal gland (adrenalectomy) is standard treatment, but some patients continue to have metabolic health problems after surgery.
This randomized study will evaluate whether treatment with tirzepatide after adrenalectomy improves metabolic outcomes in patients with MACS compared with adrenalectomy alone.
Studie Overzicht
Toestand
Werving
Interventie / Behandeling
Gedetailleerde beschrijving
This prospective, randomized study will enroll adults with MACS and elevated blood pressure who are undergoing unilateral adrenalectomy. Following surgery, participants will be randomized in a 1:1 ratio to one of two groups: adrenalectomy alone or adrenalectomy followed by tirzepatide therapy for 12 months. Tirzepatide will be prescribed and managed by the study team in accordance with current standard-of-care practices, including routine clinical monitoring and dose adjustments.
The primary focus of the study is to evaluate blood pressure control at 12 months. Secondary outcomes include change in body weight, body mass index, glycemic control, medication burden, and patient-reported quality of life. This study aims to generate preliminary data on the feasibility, safety, and potential additive metabolic benefits of combining pharmacologic incretin-based therapy with surgical management of MACS.
Studietype
Ingrijpend
Inschrijving (Geschat)
34
Fase
- Fase 2
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studiecontact
- Naam: Meghan Kelley
- Telefoonnummer: 4125789429
- E-mail: hilkoml@upmc.edu
Studie Locaties
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Pennsylvania
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Pittsburgh, Pennsylvania, Verenigde Staten, 15213
- Werving
- University of Pittsburgh Medical Center
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Nee
Beschrijving
Inclusion Criteria:
- Adults aged 18 years and older
- Diagnosis of MACS, defined as morning cortisol >1.8 mcg/dL after a 1 mg dexamethasone suppression test
- Elevated blood pressure (SBP ≥120 mmHg or DBP ≥80 mmHg per the 2025 American College of Cardiology/American Heart Association [ACC/AHA] criteria, or current use of antihypertensive medication)
- BMI ≥27
- Undergoing or having undergone adrenalectomy for the treatment of MACS
Exclusion Criteria:
- Bilateral adrenal lesions
- Adrenal malignancy
- Concurrent primary aldosteronism with MACS
- Current use of GLP-1 receptor agonists
- Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2)
- Pregnancy or breastfeeding
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Actieve vergelijker: GLP-1 Treatment
GLP-1 dose of 2.5 mg once weekly for 4 weeks.
The dose will then be titrated every 4 weeks based on patient tolerance to 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg.
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Tirzepatide will be initiated at the lowest dose of 2.5 mg once weekly for 4 weeks.
The dose will then be titrated every 4 weeks based on patient tolerance to 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg.
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Actieve vergelijker: Standard of Care arm
Participants in this arm will receive standard of care management for as determined by their treating clinician.
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Participants will receive postoperative care and follow up per institutional standard-of-care practices
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Change in systolic blood pressure
Tijdsspanne: Baseline and 12 months
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Changes in blood pressure will be assessed based on patients' average blood pressure readings, mmHg
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Baseline and 12 months
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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weight
Tijdsspanne: Baseline and 12 months
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Change in participant weight, Kg
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Baseline and 12 months
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medication
Tijdsspanne: Baseline and 12 months reported in WHO defined daily doses (DDDs)
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any change in medication expressed as defined daily doses (DDDs)
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Baseline and 12 months reported in WHO defined daily doses (DDDs)
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quality of life metrics
Tijdsspanne: Baseline and 12 months
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quality of life metrics will measured using the 36-Item Short Form Health Survey (SF-36) which is a validated measure of health-related quality of life assessing eight domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health.
Each domain is scored from 0 to 100, with higher scores indicating better health status.
Domain scores may be analyzed individually or combined using standard scoring algorithms to generate the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, which are norm-based (mean 50, SD 10); higher values reflect better physical and mental health, respectively.
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Baseline and 12 months
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BMI
Tijdsspanne: Baseline and 12 months
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Any change in BMI in kg/m2
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Baseline and 12 months
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HbA1c
Tijdsspanne: Baseline and 12 months
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change in HbA1c levels
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Baseline and 12 months
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Onderzoekers
- Hoofdonderzoeker: Alaa Sada, MD, University of Pittsburgh
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Algemene publicaties
- Ebbehoj A, Li D, Kaur RJ, Zhang C, Singh S, Li T, Atkinson E, Achenbach S, Khosla S, Arlt W, Young WF, Rocca WA, Bancos I. Epidemiology of adrenal tumours in Olmsted County, Minnesota, USA: a population-based cohort study. Lancet Diabetes Endocrinol. 2020 Nov;8(11):894-902. doi: 10.1016/S2213-8587(20)30314-4.
- Morelli V, Ghielmetti A, Caldiroli A, Grassi S, Siri FM, Caletti E, Mucci F, Aresta C, Passeri E, Pugliese F, Di Giorgio A, Corbetta S, Scillitani A, Arosio M, Buoli M, Chiodini I. Mental Health in Patients With Adrenal Incidentalomas: Is There a Relation With Different Degrees of Cortisol Secretion? J Clin Endocrinol Metab. 2021 Jan 1;106(1):e130-e139. doi: 10.1210/clinem/dgaa695.
- Bancos I, Prete A. Approach to the Patient With Adrenal Incidentaloma. J Clin Endocrinol Metab. 2021 Oct 21;106(11):3331-3353. doi: 10.1210/clinem/dgab512.
- Prete A, Subramanian A, Bancos I, Chortis V, Tsagarakis S, Lang K, Macech M, Delivanis DA, Pupovac ID, Reimondo G, Marina LV, Deutschbein T, Balomenaki M, O'Reilly MW, Gilligan LC, Jenkinson C, Bednarczuk T, Zhang CD, Dusek T, Diamantopoulos A, Asia M, Kondracka A, Li D, Masjkur JR, Quinkler M, Ueland GA, Dennedy MC, Beuschlein F, Tabarin A, Fassnacht M, Ivovic M, Terzolo M, Kastelan D, Young WF Jr, Manolopoulos KN, Ambroziak U, Vassiliadi DA, Taylor AE, Sitch AJ, Nirantharakumar K, Arlt W; ENSAT EURINE-ACT Investigators*; ENSAT EURINE-ACT Investigators. Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study. Ann Intern Med. 2022 Mar;175(3):325-334. doi: 10.7326/M21-1737. Epub 2022 Jan 4.
- Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, Pelsma I, Marina L, Lorenz K, Bancos I, Arlt W, Dekkers OM. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2023 Jul 20;189(1):G1-G42. doi: 10.1093/ejendo/lvad066.
- Reimondo G, Castellano E, Grosso M, Priotto R, Puglisi S, Pia A, Pellegrino M, Borretta G, Terzolo M. Adrenal Incidentalomas are Tied to Increased Risk of Diabetes: Findings from a Prospective Study. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz284. doi: 10.1210/clinem/dgz284.
- Kanbay M, Copur S, Siriopol D, Yildiz AB, Gaipov A, van Raalte DH, Tuttle KR. Effect of tirzepatide on blood pressure and lipids: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2023 Dec;25(12):3766-3778. doi: 10.1111/dom.15272. Epub 2023 Sep 12.
- Krumholz HM, de Lemos JA, Sattar N, Linetzky B, Sharma P, Mast CJ, Ahmad NN, Bunck MC, Stefanski A. Tirzepatide and blood pressure reduction: stratified analyses of the SURMOUNT-1 randomised controlled trial. Heart. 2024 Sep 16;110(19):1165-1171. doi: 10.1136/heartjnl-2024-324170.
- Zeiger MA, Thompson GB, Duh QY, Hamrahian AH, Angelos P, Elaraj D, Fishman E, Kharlip J; American Association of Clinical Endocrinologists; American Association of Endocrine Surgeons. The American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons medical guidelines for the management of adrenal incidentalomas. Endocr Pract. 2009 Jul-Aug;15 Suppl 1:1-20. doi: 10.4158/EP.15.S1.1. No abstract available.
- Pelsma ICM, Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, Marina L, Lorenz K, Bancos I, Arlt W, Dekkers OM. Comorbidities in mild autonomous cortisol secretion and the effect of treatment: systematic review and meta-analysis. Eur J Endocrinol. 2023 Oct 17;189(4):S88-S101. doi: 10.1093/ejendo/lvad134.
- Vanek C, Loriaux L. The 1 mg overnight dexamethasone suppression test: a danger to the adrenal gland? Curr Opin Endocrinol Diabetes Obes. 2022 Aug 1;29(4):403-405. doi: 10.1097/MED.0000000000000752.
- Kelsall A, Iqbal A, Newell-Price J. Adrenal incidentaloma: cardiovascular and metabolic effects of mild cortisol excess. Gland Surg. 2020 Feb;9(1):94-104. doi: 10.21037/gs.2019.11.19.
- Araujo-Castro M, Reincke M, Lamas C. Epidemiology and Management of Hypertension and Diabetes Mellitus in Patients with Mild Autonomous Cortisol Secretion: A Review. Biomedicines. 2023 Nov 22;11(12):3115. doi: 10.3390/biomedicines11123115.
- Prete A, Bancos I. Mild autonomous cortisol secretion: pathophysiology, comorbidities and management approaches. Nat Rev Endocrinol. 2024 Aug;20(8):460-473. doi: 10.1038/s41574-024-00984-y. Epub 2024 Apr 22.
- Sojat AS, Dunjic-Kostic B, Marina LV, Ivovic M, Radonjic NV, Kendereski A, Cirkovic A, Tancic-Gajic M, Arizanovic Z, Mihajlovic S, Vujovic S. Depression: another cortisol-related comorbidity in patients with adrenal incidentalomas and (possible) autonomous cortisol secretion. J Endocrinol Invest. 2021 Sep;44(9):1935-1945. doi: 10.1007/s40618-021-01509-4. Epub 2021 Feb 2.
- Reimondo G, Puglisi S, Pia A, Terzolo M. Autonomous hypercortisolism: definition and clinical implications. Minerva Endocrinol. 2019 Mar;44(1):33-42. doi: 10.23736/S0391-1977.18.02884-5. Epub 2018 Jul 2.
- Yip L, Duh QY, Wachtel H, Jimenez C, Sturgeon C, Lee C, Velazquez-Fernandez D, Berber E, Hammer GD, Bancos I, Lee JA, Marko J, Morris-Wiseman LF, Hughes MS, Livhits MJ, Han MA, Smith PW, Wilhelm S, Asa SL, Fahey TJ 3rd, McKenzie TJ, Strong VE, Perrier ND. American Association of Endocrine Surgeons Guidelines for Adrenalectomy: Executive Summary. JAMA Surg. 2022 Oct 1;157(10):870-877. doi: 10.1001/jamasurg.2022.3544.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
27 juli 2026
Primaire voltooiing (Geschat)
31 juli 2028
Studie voltooiing (Geschat)
31 december 2028
Studieregistratiedata
Eerst ingediend
1 mei 2026
Eerst ingediend dat voldeed aan de QC-criteria
1 mei 2026
Eerst geplaatst (Werkelijk)
7 mei 2026
Updates van studierecords
Laatste update geplaatst (Werkelijk)
30 juli 2026
Laatste update ingediend die voldeed aan QC-criteria
28 juli 2026
Laatst geverifieerd
1 juli 2026
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- STUDY25030073
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
NEE
Beschrijving IPD-plan
Individual participant data (IPD) will not be publicly shared because the study involves a small sample size from a single center with detailed clinical, laboratory, and imaging data, which may pose a risk of participant re-identification despite de-identification procedures.
Aggregate results will be reported in peer-reviewed publications.
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Ja
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
product vervaardigd in en geëxporteerd uit de V.S.
Nee
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .