IMPACT-MACS Study: Investigating the Mechanisms, Pathophysiology, and Cardiometabolic Treatment in Mild Autonomous Cortisol Secretion
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Change in Insulin Sensitivity (M-value), mg/kg/min
研究概览
简要总结
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:
- Does adrenalectomy or semaglutide improve insulin resistance more in people with MACS?
- How do these treatments change cortisol patterns and other cardiometabolic risk factors?
- Do people with MACS respond differently to semaglutide compared to matched adults without MACS?
Participants will:
- Receive either adrenalectomy or semaglutide if they have MACS, or semaglutide if they are matched controls
- Complete clinic visits and phone visits over about 26-30 weeks
- 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
详细描述
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:
- a randomized controlled trial comparing adrenalectomy to semaglutide in MACS, and
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm 1: Adrenalectomy (MACS)
Adults with mild autonomous cortisol secretion (MACS) who are clinically eligible for adrenalectomy undergo unilateral adrenalectomy as part of standard care. Participants complete all metabolic assessments before and after treatment.
干预措施: Intervention 1: Adrenalectomy (Procedure)
Arm 2: Semaglutide (MACS)
Adults with MACS receive once-weekly semaglutide for 26 weeks using FDA-approved weight-management dosing. Participants undergo the same assessments as the surgery group.
干预措施: Intervention 2: Semaglutide (Drug)
Arm 3: Semaglutide (Matched Controls)
Matched adults without adrenal tumors receive semaglutide using the same dosing schedule as MACS participants. This arm allows comparison of semaglutide responses between individuals with and without cortisol dysregulation.
干预措施: Intervention 2: Semaglutide (Drug)
结局指标
主要结局
Change in Insulin Sensitivity (M-value), mg/kg/min
时间窗: Baseline to Week 26
Hyperinsulinemic-euglycemic clamp
次要结局
- Change in fasting plasma glucose, mg/dL(Baseline to Week 26)
- Change in hemoglobin A1C, %(Baseline to Week 26)
- Change in fasting insulin, µU/mL(Baseline to Week 26)
- Change in glucagon, pg/mL(Baseline to Week 26)
- Change in c-peptide, nmol/L(Baseline to Week 26)
- Change in IGF-1, ng/mL(Baseline to Week 26)
- Change in IGF-II, ng/mL(Baseline to Week 26)
- Change in IGFBP-1, ng/mL(Baseline to Week 26)
- Change in leptin, ng/mL(Baseline to Week 26)
- Change in adiponectin, μg/mL(Baseline to Week 26)
- % of patients with normal dexamethasone suppression test, %(Baseline to Week 26)
- Change in steroid profile, ng/24h(Baseline to Week 26)
- Mean change in systolic BP, mmHg(Baseline to Week 26)
- Mean change in diastolic BP, mmHg(Baseline to Week 26)
- Change in cholesterol, mg/dL(Baseline to Week 26)
- Change in Free Fatty Acids, mmol/L(Baseline to Week 26Baseline to Week 26)
- Change in C-reactive protein, pg/mL(Baseline to Week 26)
- Change in TNF-alpha, pg/mL(Baseline to Week 26)
- Change in Interleukin-1, pg/mL(Baseline to Week 26)
- Change in Interleukin-6, pg/mL(Baseline to Week 26)
- Change in body weight, kg(Baseline to Week 26)
- Change in BMI, kg/m2(Baseline to Week 26)
- Change in waist circumference, cm(Baseline to Week 26)
- Change in fat area, cm2(Baseline to Week 26)
- Change in muscle area, cm2(Baseline to Week 26)
- Change in bone mineral density, mg/cm³(Baseline to Week 26)
- Change in chair rise test, stands/30s(Baseline to Week 26)
- Change in Hand Grip Strength, kg(Baseline to Week 26)
- Change in overall quality of life, score(Baseline to Week 26)
- Change in disease-specific QoL, score(Baseline to Week 26)
- Change in mood, score(Baseline to Week 26)
- Change in cognition, seconds(Baseline to Week 26)
- Change in sleep, score(Baseline to Week 26)
- Change in frailty, score(Baseline to Week 26)
- Change in eating behavior, score(Baseline to Week 26)
- Adverse Events and Serious Adverse Events(Baseline through Week 30)
研究者
Oksana Hamidi, DO, MSCS
Associate Professor
University of Texas Southwestern Medical Center