IMPACT-MACS: Adrenalectomy vs Semaglutide for Metabolic Outcomes in Mild Autonomous Cortisol Secretion

Официальное название

IMPACT-MACS Study: Investigating the Mechanisms, Pathophysiology, and Cardiometabolic Treatment in Mild Autonomous Cortisol Secretion

Обзор

The goal of this study is to learn how two treatments-adrenalectomy (surgical removal of an adrenal gland) and semaglutide (a medication used for weight management)-affect insulin resistance and cortisol regulation in adults with mild autonomous cortisol secretion (MACS). The study will also learn how these treatments impact body composition, blood pressure, cholesterol, inflammation, muscle strength, and quality of life. The main questions the study aims to answer are: 1. Does adrenalectomy or semaglutide improve insulin resistance more in people with MACS? 2. How do these treatments change cortisol patterns and other cardiometabolic risk factors? 3. Do people with MACS respond differently to semaglutide compared to matched adults without MACS? Participants will: 1. Receive either adrenalectomy or semaglutide if they have MACS, or semaglutide if they are matched controls 2. Complete clinic visits and phone visits over about 26-30 weeks 3. Undergo metabolic testing such as blood tests, urine steroid profiling, body composition scans, blood pressure monitoring, muscle strength testing, and questionnaires about health and well-being

Подробное описание

This single-center, prospective, interventional study evaluates metabolic responses to surgical versus medical treatment in adults with mild autonomous cortisol secretion (MACS). The study includes:

1. a randomized controlled trial comparing adrenalectomy to semaglutide in MACS, and 2. a parallel matched case-control comparison evaluating semaglutide effects in MACS versus matched controls without adrenal tumors.

The primary objective is to compare changes in insulin sensitivity measured by hyperinsulinemic-euglycemic clamp (M-value) from baseline to week 26. Secondary outcomes include cortisol dynamics, steroid profiling, cardiometabolic biomarkers, body composition, blood pressure, muscle strength, and patient-reported quality of life.

Semaglutide is administered within its FDA-approved indication for weight management; adrenalectomy is standard of care. No investigational drugs or devices are used, and no IND is required.

Вмешательства

• Процедура Intervention 1: Adrenalectomy
  Surgical removal of one adrenal gland performed by an endocrine surgeon following institutional standard-of-care practices. Includes postoperative monitoring for adrenal insufficiency and routine clinical follow-up.
• Препарат Intervention 2: Semaglutide
  Once-weekly subcutaneous semaglutide administered according to FDA-approved titration for chronic weight management (0.25 mg to 2.4 mg weekly as tolerated). Participants receive training on injection technique, dose escalation, and safety monitoring.

Первичные конечные точки

• Change in Insulin Sensitivity (M-value), mg/kg/min [Срок оценки: Baseline to Week 26]

Вторичные конечные точки (12)

• Change in fasting plasma glucose, mg/dL [Срок оценки: Baseline to Week 26]
• Change in hemoglobin A1C, % [Срок оценки: Baseline to Week 26]
• Change in fasting insulin, µU/mL [Срок оценки: Baseline to Week 26]
• Change in glucagon, pg/mL [Срок оценки: Baseline to Week 26]
• Change in c-peptide, nmol/L [Срок оценки: Baseline to Week 26]
• Change in IGF-1, ng/mL [Срок оценки: Baseline to Week 26]
• Change in IGF-II, ng/mL [Срок оценки: Baseline to Week 26]
• Change in IGFBP-1, ng/mL [Срок оценки: Baseline to Week 26]
• Change in leptin, ng/mL [Срок оценки: Baseline to Week 26]
• Change in adiponectin, μg/mL [Срок оценки: Baseline to Week 26]
• % of patients with normal dexamethasone suppression test, % [Срок оценки: Baseline to Week 26]
• Change in steroid profile, ng/24h [Срок оценки: Baseline to Week 26]

Критерии участия

Критерии включения

• Adults ≥18 years
• MACS groups: adrenal adenoma + DST cortisol >1.8 µg/dL + no overt Cushing + eligible for adrenalectomy
• Willingness to postpone surgery 6 months if randomized
• Controls: no adrenal abnormalities + normal DST + BMI ≥27 + ≥2 cardiometabolic conditions
• Stable medication doses for ≥4 weeks
• Negative pregnancy test if applicable

Критерии исключения

• Prior GLP-1 RA within 90 days
• Weight change >5 kg in past 90 days
• Prior obesity/diabetes surgery
• Type 1 diabetes or other diabetes types
• Severe organ disease
• Recent pancreatitis
• Pregnancy, breastfeeding
• Contraindication to semaglutide
• Contraindication to surgery delay
• Chronic glucocorticoid use

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Texas Southwestern Medical Center — Dallas

Публикации

• Yozamp N, Vaidya A. Assessment of mild autonomous cortisol secretion among incidentally discovered adrenal masses. Best Pract Res Clin Endocrinol Metab. 2021 Jan;35(1):101491. doi: 10.1016/j.beem.2021.101491. Epub 2021 Feb 6. PMID 33593680
• 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. PMID 34260734
• 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 J PMID 34978855
• 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. PMID 33065059
• 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. PMID 37318239
• Kolanska K, Owecki M, Nikisch E, Sowinski J. High prevalence of obesity in patients with non-functioning adrenal incidentalomas. Neuro Endocrinol Lett. 2010;31(3):418-22. PMID 20588242
• 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. PMID 31900474
• Bovio S, Cataldi A, Reimondo G, Sperone P, Novello S, Berruti A, Borasio P, Fava C, Dogliotti L, Scagliotti GV, Angeli A, Terzolo M. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Invest. 2006 Apr;29(4):298-302. doi: 10.1007/BF03344099. PMID 16699294

Идентификаторы

NCT: NCT07361874 · STU20251717 · 1K23DK142038-01A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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