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)
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.
연구 개요
상태
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Beckey Trinh, PD, MD, PhD
- 전화번호: +41612655078
- 이메일: beckey.trinh@usb.ch
연구 장소
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Basel, 스위스
- University Hospital Basel, Clinic of Endocrinology, Diabetology & Metabolism
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연락하다:
- Beckey Trinh, PD, MD, PhD
- 전화번호: +41612655078
- 이메일: beckey.trinh@usb.ch
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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. |
1 mg film-coated tablet, orally once daily at 18:00; optional single escalation to 2 mg after 14 days; 12 weeks. blinded stress/sick-day (rescue) dosing only, per written instructions |
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위약 비교기: Placebo
Placebo once daily at 18:00 for 12 weeks, plus blinded placebo for hydrocortisone (identical schedule). |
placebo tablet, orally once daily at 18:00; 12 weeks placebo tablet for stress-dosing regimen |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change from baseline in HbA1c at week 12
기간: Baseline and week 12
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Between-group difference in HbA1c change (%). Time Frame: Baseline and week 12 |
Baseline and week 12
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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CGM Time in Range (3.9-10.0 mmol/L, %)
기간: baseline, week 6 and week 12
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14-day windows preceding baseline, week 6 and week 12. |
baseline, week 6 and week 12
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CGM Time in Tight Range (3.9-7.8 mmol/L, %)
기간: baseline, week 6 and week 12
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14-day windows preceding baseline, week 6 and week 12. |
baseline, week 6 and week 12
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CGM Time below range (<3.9 and <3.0 mmol/L, %)
기간: baseline, week 6 and week 12
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14-day windows preceding baseline, week 6 and week 12 |
baseline, week 6 and week 12
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CGM Time above range (>10.0 and >13.9 mmol/L, %)
기간: baseline, week 6 and week 12
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14-day windows preceding baseline, week 6 and week 12. |
baseline, week 6 and week 12
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Change in blood pressure
기간: Baseline and week 12
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Baseline and week 12
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Change in lipid profile
기간: Baseline and week 12
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Baseline and week 12
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Change in body weight and waist/hip circumference
기간: Baseline and week 12
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Baseline and week 12
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Change in DXA-derived body composition
기간: Baseline and week 12
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Baseline and week 12
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Proportion of participants requiring reduction of hypoglycemia-causing therapy (insulin/sulfonylurea)
기간: Baseline to week 12
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Baseline to week 12
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Change in antihypertensive medication
기간: Baseline to week 12
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Baseline to week 12
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Change in plasma cortisol
기간: Baseline and week 12
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Baseline and week 12
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Change in salivary cortisol
기간: Baseline to week 12
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Baseline to week 12
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Change in 24-h urinary cortisol
기간: Baseline and week 12
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Baseline and week 12
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Change from baseline in health-related quality of life (SF-36)
기간: Baseline and week 12
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8 subscales + physical/mental component summaries, 0-100, higher = better |
Baseline and week 12
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Change from baseline in disease-specific quality of life (CushingQoL questionnaire)
기간: Baseline and week 12
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higher = better |
Baseline and week 12
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Change from baseline in sleep quality (Pittsburgh Sleep Quality Index, PSQI)
기간: Baseline and week 12
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global score 0-21, higher = worse sleep |
Baseline and week 12
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change from baseline in bone mineral density by DXA (g/cm²)
기간: Baseline and week 12
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Baseline and week 12
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Change from baseline in serum β-CTX (C-terminal telopeptide of type I collagen)
기간: Baseline and week 12
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Baseline and week 12
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Change from baseline in serum P1NP (procollagen type I N-terminal propeptide)
기간: Baseline and week 12
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Baseline and week 12
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Change from baseline in total alkaline phosphatase (U/L)
기간: Baseline and week 12
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Baseline and week 12
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Change from baseline in bone-specific alkaline phosphatase
기간: Baseline and week 12
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Baseline and week 12
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Change from baseline in the clinical Cushing severity score
기간: Baseline and week 12
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Li et al. 2023 clinical severity score; 0-22, higher = more severe |
Baseline and week 12
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Change from baseline in handgrip strength
기간: Baseline and week 12
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hand dynamometer; kg, best of three |
Baseline and week 12
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Change from baseline in the five-times sit-to-stand test
기간: Baseline and week 12
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seconds; lower = better |
Baseline and week 12
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Serum interleukin-6
기간: Baseline and week 12
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Baseline and week 12
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Serum TNF-α
기간: Baseline and week 12
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Baseline and week 12
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Serum IL-1Ra
기간: Baseline and week 12
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Baseline and week 12
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Serum hs-CRP
기간: Baseline and week 12
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Baseline and week 12
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Plasma and 24-h urinary steroid metabolome
기간: Baseline and week 12
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Baseline and week 12
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Circadian clock-gene expression (whole-blood RNA)
기간: Baseline and week 12
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Baseline and week 12
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공동 작업자 및 조사자
스폰서
수사관
- 수석 연구원: Beckey Trinh, PD, MD, PhD, University Hospital, Basel, Switzerland
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- GLYCOSIL-MACS
- 2026-01499 (기타 식별자: BASEC / Ethics Committee Northwest and Central Switzerland, EKNZ)
- 205.123670 (기타 식별자: Swissmedic)
- SNCTP000007077 (기타 식별자: Swiss National Clinical Trials Portal)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
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.
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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