Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS)

NCT07247058 | Recruiting Phase 4 FDA Drug

• 1 other identifier: IRB00511675
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Autonomous Cortisol Secretion (MACS)

Keywords

MACS; Mild Autonomous Cortisol Secretion; Adrenal Adenoma; Osilodrostat; Isturisa; Body Composition; Metabolic Outcomes; Subclinical Cushing Syndrome; Adrenal hyperplasia; Carotid intima thickness; Bone mineral density; Hypertension; Glycemic control

Outcome Measures

Primary Outcomes (5)

• Change in fasting glucose, HbA1c

  glycemic control: fasting glucose, HbA1c

  Baseline, and then every 3 months up to 2 years

• Change in bone mineral density (g/cm²)

  Bone mineral density (g/cm²) measured by DEXA scan.

  Baseline, 1 year, and 2 years

• Change in body weight (kg) from baseline during Isturisa treatment

  Change in body weight will be measured at baseline and every follow-up visit (approximately every 3 months) throughout the 2-year treatment period with Isturisa.

  Baseline and every 3 months up to 2 years

• Change in lipid profile from baseline during Isturisa treatment

  Serum lipid profile (LDL-C, HDL-C, total cholesterol, triglycerides) will be assessed at baseline and every follow-up visit (approximately every 3 months) during the 2-year treatment period.

  Baseline and every 3 months up to 2 years

• Change in body composition (kg)

  Body composition including lean mass and fat mass (kg) measured by DEXA scan.

  baseline, 1 year and 2 years

Secondary Outcomes (4)

• Change in Quality of Life as assessed by Short Form -36 (SF-36)

  Baseline and every 3 months up to 2 years

• Change in carotid intima-media thickness (CIMT)

  Baseline, 1 year, and 2 years

• Change in adrenal adenoma/hyperplasia size (mm)

  Baseline, 1 year, and 2 years

• Change in Depression Scores as assessed by the Beck Depression Inventory-II

  Baseline and every 3 months up to 2 years

Other Outcomes (1)

• Change in Inflammatory Biomarkers

  Baseline and every 3 months up to 2 years

Study Arms (1)

Isturisa Treatment Arm

EXPERIMENTAL

Participants diagnosed with Mild Autonomous Cortisol Secretion (MACS) will receive Osilodrostat (Isturisa) as an investigational treatment. The intervention aims to evaluate comorbidities associated with MACS after the initiation of osilodrostat(Isturisa).

Drug: Osilodrostat (Isturisa)

Interventions

Osilodrostat (Isturisa) DRUG

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.

Also known as: Osilodrostat, Isturisa, LCI699

Isturisa Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Recordati Rare Diseases Inc: collaborator

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

RECRUITING

Related Publications (14)

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• Czapla-Iskrzycka A, Swiatkowska-Stodulska R, Sworczak K. Comorbidities in Mild Autonomous Cortisol Secretion - A Clinical Review of Literature. Exp Clin Endocrinol Diabetes. 2022 Sep;130(9):567-576. doi: 10.1055/a-1827-4113. Epub 2022 Jul 11.

  PMID: 35817047 RESULT

• Vaidya A, Hamrahian A, Bancos I, Fleseriu M, Ghayee HK. THE EVALUATION OF INCIDENTALLY DISCOVERED ADRENAL MASSES. Endocr Pract. 2019 Feb;25(2):178-192. doi: 10.4158/DSCR-2018-0565.

  PMID: 30817193 RESULT

• 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 RESULT

• Trandafir AI, Ghemigian A, Ciobica ML, Nistor C, Gurzun MM, Nistor TVI, Petrova E, Carsote M. Diabetes Mellitus in Non-Functioning Adrenal Incidentalomas: Analysis of the Mild Autonomous Cortisol Secretion (MACS) Impact on Glucose Profile. Biomedicines. 2024 Jul 18;12(7):1606. doi: 10.3390/biomedicines12071606.

  PMID: 39062179 RESULT

• Zavatta G, Vicennati V, Altieri P, Tucci L, Colombin G, Coscia K, Mosconi C, Balacchi C, Fanelli F, Malagrino M, Magagnoli M, Golfieri R, Pagotto U, Di Dalmazi G. Mild autonomous cortisol secretion in adrenal incidentalomas and risk of fragility fractures: a large cross-sectional study. Eur J Endocrinol. 2023 Apr 4;188(4):343-352. doi: 10.1093/ejendo/lvad038.

  PMID: 36952249 RESULT

• Delivanis DA, Athimulam S, Bancos I. Modern Management of Mild Autonomous Cortisol Secretion. Clin Pharmacol Ther. 2019 Dec;106(6):1209-1221. doi: 10.1002/cpt.1551. Epub 2019 Aug 6.

  PMID: 31206616 RESULT

MeSH Terms

Conditions

ACTH Syndrome, Ectopic; Adrenal Hyperplasia, Congenital; Hypertension

Interventions

Osilodrostat

Condition Hierarchy (Ancestors)

Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Neoplasms; Adrenogenital Syndrome; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Gonadal Disorders; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Amir Hamrahian, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pooneh Jabbaripour Sarmadian, MD

CONTACT

667-208-8367; pjabbar1@jh.edu

Tony Keyes

CONTACT

410-550-6259; akeyes1@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label study. No parties are masked
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-arm, interventional study in which all enrolled participants with MACS will receive Osilodrostat (Isturisa). The patients will be evaluated for the impact of Isturisa on clinical features and comorbidities associated with MACS.

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: November 25, 2025
• Study Start: February 2, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)