Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS)

Официальное название

Isturisa in Management of Mild Autonomous Cortisol Secretion (MACS)

Обзор

To characterize the impact of Isturisa on clinical features and comorbidities associated with MACS. The investigators hypothesize that patients treated with Isturisa will exhibit significantly better metabolic indicators (such as fasting glucose, HbA1c, and lipid profile), blood pressure, weight, body composition and bone mineral density than at Baseline. The investigators also assess the effect of Isturisa on quality of life and psychological symptoms in patients with MACS. The investigators hypothesize that treatment with Isturisa will lead to significant improvements in quality-of-life scores and reductions in depression scores compared to Baseline.

Подробное описание

Mild autonomous cortisol secretion (MACS) is diagnosed in up to 48% of patients with incidentally discovered adrenal tumors or hyperplasia. Based on the finding of adrenal masses in 5% of adults undergoing cross-sectional imaging, the overall prevalence of MACS is about 1-2%. MACS is characterized by autonomous cortisol secretion without the overt symptoms of Cushing syndrome. It is usually associated with low ACTH and DHEAS levels as an indicator of autonomous cortisol secretion. The European Society of Endocrinology-European Network for the Study of Adrenal Tumors (ESE-ENSAT) and the American Association of Clinical Endocrinology (AACE) recommend a cortisol \>1.8 μg/dL after 1 mg-DST to define MACS. Several metabolic abnormalities are associated with MACS, including increased cardiovascular disease, mood alteration, hypertension, osteoporosis, hyperglycemia, obesity, weight gain, and lipid abnormalities. Additionally, increased mortality has been reported in MACS patients. Given these complications and increased mortality, there is a need for effective management and treatment options for MACS.

This research aims to evaluate the efficacy and safety of Isturisa in patients with MACS to address the current gap in treatment strategies. By assessing how effectively Isturisa improves cardiometabolic disorders and monitoring its safety profile, the research will seek to provide a clearer understanding of its role as a treatment option in MACS patients who are not a surgical candidate or do not want to pursue surgery. This evaluation is crucial for developing more effective treatment options and improving management strategies for MACS, ultimately contributing to better patient management.

Вмешательства

• Препарат Osilodrostat (Isturisa)
  The intervention aims to evaluate the impact of osilodrostat on cardiometabolic outcomes, bone mineral density, body composition, adrenal tumor size or hyperplasia, and biochemical markers of cortisol excess.

Первичные конечные точки

• Change in fasting glucose, HbA1c [Срок оценки: Baseline, and then every 3 months up to 2 years]
• Change in bone mineral density (g/cm²) [Срок оценки: Baseline, 1 year, and 2 years]
• Change in body weight (kg) from baseline during Isturisa treatment [Срок оценки: Baseline and every 3 months up to 2 years]
• Change in lipid profile from baseline during Isturisa treatment [Срок оценки: Baseline and every 3 months up to 2 years]
• Change in body composition (kg) [Срок оценки: baseline, 1 year and 2 years]

Вторичные конечные точки (4)

• Change in Quality of Life as assessed by Short Form -36 (SF-36) [Срок оценки: Baseline and every 3 months up to 2 years]
• Change in carotid intima-media thickness (CIMT) [Срок оценки: Baseline, 1 year, and 2 years]
• Change in adrenal adenoma/hyperplasia size (mm) [Срок оценки: Baseline, 1 year, and 2 years]
• Change in Depression Scores as assessed by the Beck Depression Inventory-II [Срок оценки: Baseline and every 3 months up to 2 years]

Критерии участия

Критерии включения

• Adults aged ≥18 years.
• Diagnosis of mild autonomous cortisol secretion (MACS) defined by:
• Serum cortisol >1.8 µg/dL after 1 mg overnight dexamethasone suppression test (DST).
• Presence of adrenal adenoma confirmed by imaging (CT or MRI).
• Ability to provide informed consent.
• Willingness to undergo study procedures including DEXA scan and laboratory assessments.

Критерии исключения

• Known diagnosis of Cushing's syndrome or overt hypercortisolism.
• Current or recent (within 3 months) treatment with glucocorticoids or medications affecting cortisol production (e.g., ketoconazole, metyrapone).
• Severe hepatic impairment or renal failure.
• Pregnancy or breastfeeding.
• Known allergy or contraindication to osilodrostat (Isturisa).
• Participation in another interventional clinical trial within the last 30 days.
• Any medical or psychiatric condition that, in the investigator's judgment, may interfere with study participation or safety.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Johns Hopkins University School of Medicine — Baltimore

Публикации

• Feldman D. Ketoconazole and other imidazole derivatives as inhibitors of steroidogenesis. Endocr Rev. 1986 Nov;7(4):409-20. doi: 10.1210/edrv-7-4-409. No abstract available. PMID 3536461
• Martino M, Aboud N, Lucchetti B, Salvio G, Arnaldi G. Osilodrostat oral tablets for adults with Cushing's disease. Expert Rev Endocrinol Metab. 2022 Mar;17(2):99-109. doi: 10.1080/17446651.2022.2044789. Epub 2022 Feb 28. PMID 35220871
• Tibblin S, Dymling JF, Ingemansson S, Telenius-Berg M. Unilateral versus bilateral adrenalectomy in multiple endocrine neoplasia IIA. World J Surg. 1983 Mar;7(2):201-8. doi: 10.1007/BF01656143. No abstract available. PMID 6135282
• Ma L, Yin L, Hu Q. Therapeutic compounds for Cushing's syndrome: a patent review (2012-2016). Expert Opin Ther Pat. 2016 Nov;26(11):1307-1323. doi: 10.1080/13543776.2016.1217331. Epub 2016 Jul 30. PMID 27454103
• Ren X, Nan M, Zhang X. Evaluating the efficacy of surgical and conservative approaches in mild autonomous cortisol secretion: a meta-analysis. Front Endocrinol (Lausanne). 2024 Jul 17;15:1399311. doi: 10.3389/fendo.2024.1399311. eCollection 2024. PMID 39086899
• Sbardella E, Minnetti M, D'Aluisio D, Rizza L, Di Giorgio MR, Vinci F, Pofi R, Giannetta E, Venneri MA, Vestri A, Morelli S, Lenzi A, Isidori AM. Cardiovascular features of possible autonomous cortisol secretion in patients with adrenal incidentalomas. Eur J Endocrinol. 2018 May;178(5):501-511. doi: 10.1530/EJE-17-0986. Epub 2018 Mar 6. PMID 29510982
• Patrova J, Kjellman M, Wahrenberg H, Falhammar H. Increased mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: a 13-year retrospective study from one center. Endocrine. 2017 Nov;58(2):267-275. doi: 10.1007/s12020-017-1400-8. Epub 2017 Sep 8. PMID 28887710
• 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. PMID 37801655

Идентификаторы

NCT: NCT07247058 · IRB00511675

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗