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Osilodrostat for Glycemic Control in Mild Autonomous Cortisol Secretion (MACS) With Difficult-To-Control Type 2 Diabetes - A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study (GLYCOSIL-MACS)

2026年11月1日 更新者：Beckey Trinh

This single-centre, randomized, double-blind, placebo-controlled phase 2 trial investigates whether lowering cortisol with osilodrostat improves blood-glucose control in adults with mild autonomous cortisol secretion (MACS) and difficult-to-control type 2 diabetes. Forty-four participants are randomly assigned 1:1 to osilodrostat or matching placebo, taken once daily for 12 weeks, together with a blinded hydrocortisone/placebo for stress (sick-day) dosing. The primary outcome is the change in HbA1c from baseline to week 12; secondary outcomes include continuous glucose monitoring (CGM) metrics, cardiometabolic parameters, cortisol measures and quality of life. Participants are followed for a safety visit 4 weeks after the end of treatment.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

MACS is a common, mild form of endogenous hypercortisolism that may adversely affect glucose metabolism. In participants with confirmed MACS and difficult-to-control type 2 diabetes, this trial tests whether pharmacological cortisol reduction with osilodrostat improves glycaemic control. After a screening visit and a 14-day CGM run-in, participants are randomized 1:1 to osilodrostat 1 mg once daily at 18:00 (single optional escalation to 2 mg after 14 days, safety-guided) or matching placebo for 12 weeks; both arms receive a blinded hydrocortisone/placebo for stress dosing (double-dummy). Background glucose- and blood-pressure-lowering therapy is continued and adjusted only per predefined safety algorithms. Assessments include HbA1c, continuous glucose monitoring, blood pressure, lipids, anthropometrics, DXA body composition and bone density, plasma/salivary/urinary cortisol, quality-of-life and sleep questionnaires, and safety laboratory and ECG monitoring. The primary analysis is an ANCOVA of the change in HbA1c at week 12 in the intention-to-treat population under a treatment-policy estimand; CGM endpoints are analysed with mixed-effects models for repeated measures.

研究类型

介入性

注册 (估计的)

44

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

学习地点

  • 瑞士
      • Basel、瑞士
        • University Hospital Basel, Clinic of Endocrinology, Diabetology & Metabolism
        • 接触：

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 74年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Age 18 to <75 years.
  • Confirmed MACS per ESE 2023 guidelines: serum cortisol >50 nmol/L after 1 mg dexamethasone suppression test, low ACTH and DHEAS, and uni-/bilateral adrenal adenoma(s) or macronodular/micronodular/diffuse bilateral adrenal hyperplasia on CT or MRI.
  • Morning serum cortisol >300 nmol/L.
  • Difficult-to-control type 2 diabetes: HbA1c >7.0% despite one of - ≥3 glucose-lowering medications; insulin plus ≥1 glucose-lowering medication; ≥2 glucose-lowering medications and ≥1 micro-/macrovascular complication; or ≥2 glucose-lowering and ≥2 blood-pressure-lowering medications.
  • Stable background pharmacotherapy for ≥4 weeks before the first study visit.
  • For persons of childbearing potential: agreement to abstinence or contraception with a failure rate ≤1%/year during treatment and for 1 month after the last dose.

Exclusion Criteria:

  • Age ≥75 years (osilodrostat not sufficiently studied in this age group per the SmPC).
  • Known hypersensitivity to osilodrostat, its excipients, or the placebo.
  • Planned adrenalectomy before completion of the study.
  • Malignant adrenal tumour.
  • Type 1 diabetes; new-onset diabetes (<1 year).
  • Systemic glucocorticoid therapy within 3 months, or planned use.
  • Current/recent intake of medications affecting adrenal steroidogenesis or cortisol assessment.
  • Concomitant therapy with clinically relevant drug-drug interactions with osilodrostat (strong CYP3A4 inhibitors; strong CYP3A4/CYP2B6 inducers; QT-prolonging medicinal products).
  • Participation in another interventional trial within the last 30 days.
  • Pregnancy or breastfeeding; WOCBP unwilling to use highly effective contraception.
  • Excessive alcohol consumption; severe untreated sleep apnea; night-shift work.
  • Severe psychiatric, medical or surgical illness.
  • Severe renal impairment (eGFR < 30 mL/min/1.73 m²), hemodialysis or end-stage renal disease.
  • Liver cirrhosis Child-Pugh B or C.
  • Refractory hypokalemia or hypomagnesemia (not correctable to K ≥4.0 and Mg ≥1.0 mmol/L before first dose).
  • QTc > 480 ms on baseline ECG, or known congenital long QT syndrome.
  • Uncontrolled arterial hypertension (≥ 160/100 mmHg despite therapy)
  • Uncontrolled thyroid disease
  • Severe cardiovascular disease (NYHA class III-IV heart failure, myocardial infarction or unstable angina within the previous 6 months, or clinically significant arrhythmia)
  • History of breast or endometrial carcinoma

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
实验性的：Osilodrostat

Osilodrostat 1 mg once daily at 18:00 for 12 weeks (single optional escalation to 2 mg after 14 days), plus blinded hydrocortisone 10 mg for stress/sick-day dosing only.
药品：Osilodrostat (Isturisa)

1 mg film-coated tablet, orally once daily at 18:00; optional single escalation to 2 mg after 14 days; 12 weeks.

药品：hydrocortisone 10mg

blinded stress/sick-day (rescue) dosing only, per written instructions
安慰剂比较：Placebo

Placebo once daily at 18:00 for 12 weeks, plus blinded placebo for hydrocortisone (identical schedule).
药品：Placebo

placebo tablet, orally once daily at 18:00; 12 weeks

药品：Placebo (for hydrocortisone)

placebo tablet for stress-dosing regimen

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Change from baseline in HbA1c at week 12
大体时间：Baseline and week 12

Between-group difference in HbA1c change (%). Time Frame: Baseline and week 12
Baseline and week 12

次要结果测量

结果测量
措施说明
大体时间
CGM Time in Range (3.9-10.0 mmol/L, %)
大体时间：baseline, week 6 and week 12

14-day windows preceding baseline, week 6 and week 12.
baseline, week 6 and week 12
CGM Time in Tight Range (3.9-7.8 mmol/L, %)
大体时间：baseline, week 6 and week 12

14-day windows preceding baseline, week 6 and week 12.
baseline, week 6 and week 12
CGM Time below range (<3.9 and <3.0 mmol/L, %)
大体时间：baseline, week 6 and week 12

14-day windows preceding baseline, week 6 and week 12
baseline, week 6 and week 12
CGM Time above range (>10.0 and >13.9 mmol/L, %)
大体时间：baseline, week 6 and week 12

14-day windows preceding baseline, week 6 and week 12.
baseline, week 6 and week 12
Change in blood pressure
大体时间：Baseline and week 12
Baseline and week 12
Change in lipid profile
大体时间：Baseline and week 12
Baseline and week 12
Change in body weight and waist/hip circumference
大体时间：Baseline and week 12
Baseline and week 12
Change in DXA-derived body composition
大体时间：Baseline and week 12
Baseline and week 12
Proportion of participants requiring reduction of hypoglycemia-causing therapy (insulin/sulfonylurea)
大体时间：Baseline to week 12
Baseline to week 12
Change in antihypertensive medication
大体时间：Baseline to week 12
Baseline to week 12
Change in plasma cortisol
大体时间：Baseline and week 12
Baseline and week 12
Change in salivary cortisol
大体时间：Baseline to week 12
Baseline to week 12
Change in 24-h urinary cortisol
大体时间：Baseline and week 12
Baseline and week 12
Change from baseline in health-related quality of life (SF-36)
大体时间：Baseline and week 12

8 subscales + physical/mental component summaries, 0-100, higher = better
Baseline and week 12
Change from baseline in disease-specific quality of life (CushingQoL questionnaire)
大体时间：Baseline and week 12

higher = better
Baseline and week 12
Change from baseline in sleep quality (Pittsburgh Sleep Quality Index, PSQI)
大体时间：Baseline and week 12

global score 0-21, higher = worse sleep
Baseline and week 12

其他结果措施

结果测量
措施说明
大体时间
Change from baseline in bone mineral density by DXA (g/cm²)
大体时间：Baseline and week 12
Baseline and week 12
Change from baseline in serum β-CTX (C-terminal telopeptide of type I collagen)
大体时间：Baseline and week 12
Baseline and week 12
Change from baseline in serum P1NP (procollagen type I N-terminal propeptide)
大体时间：Baseline and week 12
Baseline and week 12
Change from baseline in total alkaline phosphatase (U/L)
大体时间：Baseline and week 12
Baseline and week 12
Change from baseline in bone-specific alkaline phosphatase
大体时间：Baseline and week 12
Baseline and week 12
Change from baseline in the clinical Cushing severity score
大体时间：Baseline and week 12

Li et al. 2023 clinical severity score; 0-22, higher = more severe
Baseline and week 12
Change from baseline in handgrip strength
大体时间：Baseline and week 12

hand dynamometer; kg, best of three
Baseline and week 12
Change from baseline in the five-times sit-to-stand test
大体时间：Baseline and week 12

seconds; lower = better
Baseline and week 12
Serum interleukin-6
大体时间：Baseline and week 12
Baseline and week 12
Serum TNF-α
大体时间：Baseline and week 12
Baseline and week 12
Serum IL-1Ra
大体时间：Baseline and week 12
Baseline and week 12
Serum hs-CRP
大体时间：Baseline and week 12
Baseline and week 12
Plasma and 24-h urinary steroid metabolome
大体时间：Baseline and week 12
Baseline and week 12
Circadian clock-gene expression (whole-blood RNA)
大体时间：Baseline and week 12
Baseline and week 12

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Beckey Trinh

合作者

RECORDATI GROUP
Bangerter-Rhyner Foundation

调查人员

  • 首席研究员：Beckey Trinh, PD, MD, PhD、University Hospital, Basel, Switzerland

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年11月1日

初级完成 (估计的)

2029年4月1日

研究完成 (估计的)

2029年10月1日

研究注册日期

首次提交

2026年9月23日

首先提交符合 QC 标准的

2026年11月1日

首次发布 (实际的)

2026年11月6日

研究记录更新

最后更新发布 (实际的)

2026年11月6日

上次提交的符合 QC 标准的更新

2026年11月1日

最后验证

2026年11月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • GLYCOSIL-MACS
  • 2026-01499 (其他标识符：BASEC / Ethics Committee Northwest and Central Switzerland, EKNZ)
  • 205.123670 (其他标识符：Swissmedic)
  • SNCTP000007077 (其他标识符：Swiss National Clinical Trials Portal)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

IPD 计划说明

Coded study data are held by the sponsor in Switzerland; only anonymised/aggregated data and the final report are shared externally, per the protocol data-protection section.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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