Tirzepatide Following Adrenalectomy in Mild Autonomous Cortisol Secretion
28. juli 2026 oppdatert av: 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.
Studieoversikt
Status
Rekruttering
Intervensjon / Behandling
Detaljert beskrivelse
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
Intervensjonell
Registrering (Antatt)
34
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiekontakt
- Navn: Meghan Kelley
- Telefonnummer: 4125789429
- E-post: hilkoml@upmc.edu
Studiesteder
-
-
Pennsylvania
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Pittsburgh, Pennsylvania, Forente stater, 15213
- Rekruttering
- University of Pittsburgh Medical Center
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Nei
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Aktiv komparator: 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.
|
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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Aktiv komparator: Standard of Care arm
Participants in this arm will receive standard of care management for as determined by their treating clinician.
|
Participants will receive postoperative care and follow up per institutional standard-of-care practices
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in systolic blood pressure
Tidsramme: Baseline and 12 months
|
Changes in blood pressure will be assessed based on patients' average blood pressure readings, mmHg
|
Baseline and 12 months
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
weight
Tidsramme: Baseline and 12 months
|
Change in participant weight, Kg
|
Baseline and 12 months
|
|
medication
Tidsramme: Baseline and 12 months reported in WHO defined daily doses (DDDs)
|
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)
|
|
quality of life metrics
Tidsramme: Baseline and 12 months
|
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.
|
Baseline and 12 months
|
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BMI
Tidsramme: Baseline and 12 months
|
Any change in BMI in kg/m2
|
Baseline and 12 months
|
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HbA1c
Tidsramme: Baseline and 12 months
|
change in HbA1c levels
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Baseline and 12 months
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Hovedetterforsker: Alaa Sada, MD, University of Pittsburgh
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
27. juli 2026
Primær fullføring (Antatt)
31. juli 2028
Studiet fullført (Antatt)
31. desember 2028
Datoer for studieregistrering
Først innsendt
1. mai 2026
Først innsendt som oppfylte QC-kriteriene
1. mai 2026
Først lagt ut (Faktiske)
7. mai 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
30. juli 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
28. juli 2026
Sist bekreftet
1. juli 2026
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- STUDY25030073
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
NEI
IPD-planbeskrivelse
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.
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Ja
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
produkt produsert i og eksportert fra USA
Nei
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