Identifying Responsible Signaling Pathway for Adrenergic Beta-3 Receptor Regulation in Human Subcutaneous White Adipose Tissue
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Glycerol Measured Catecholamine Sensitivity
研究概览
简要总结
This study will examine the gene expression of the adrenergic Beta-3 receptor (ADRB3) regulation in human subcutaneous adipose tissue before and after treatment with mirabegron, an ADRB3 agonist. Gene expression will be compared across two groups, lean and obese participants. There will be a total of three study visits: Screening/Eligibility, Pre-Dose Adipose Tissue Biopsy and Post-Dose Adipose Tissue Biopsy. Participants will be given a single dose of 100mg oral mirabegron on the day of the Post-Dose Adipose Tissue Biopsy.The trial design is a single-center, phase 1, open-label, exploratory study to examine the adipocyte gene expression in adults treated with 1 dose of 100mg oral mirabegron.
详细描述
The trial design is a single-center, phase 1, open-label, exploratory study to examine the adipocyte gene expression in adults treated with 1 dose of 100mg oral mirabegron.
This is an exploratory study to examine the effects of a single dose of mirabegron on adipocytes in insulin resistant obese individuals and lean controls. Approximately 40 patients over the age of 18 will be recruited for the study (20 obese individuals with insulin resistance and 20 lean controls).
There will be a total of three study visits: Screening/Eligibility, Pre-Dose Adipose Tissue Biopsy and Post-Dose Adipose Tissue Biopsy. All visits will take place at the ACTRI research clinic at UC San Diego. The Screening/Eligibility visit will involve collection of safety data and eligibility criteria, medical/medication history, physical exam, vitals, ECG and collection of urine and blood for safety laboratory analysis. The procedures completed at the Pre-Dose visit will be, vitals, re-review of medical history and changes since last visit, indirect calorimetry, an oral glucose tolerance test (OGTT), an adipose tissue biopsy, blood sample collection and study drug dispensing (one dose to be taken the morning of the following visit). The procedures completed at the Post-Dosing visit will be identical to those completed at the Baseline visit, except there will not be an OGTT at the Post-Dosing Visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Males and females 18-70 years old
- •Lean participants, defined as:
- •BMI <27 kg/m2
- •Normal glucose tolerance defined as fasting glucose less than 100 mg/dL or HbA1c of less than 5.7% at the time of the screening visit
- •Obese Insulin resistant participants, defined as:
- •BMI 30-40 kg/m2
- •Prediabetes defined as fasting glucose levels of 100 to 125 mg/dL or HbA1c of 5.7% to 6.4%
- •Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration
排除标准
- •Diabetes, defined as fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%, or diagnosis of diabetes
- •Pregnancy or lactation
- •Currently taking therapeutic anticoagulation which might increase risk of bleeding from fat biopsy (e.g., warfarin, direct oral anticoagulants)
- •History of eating disorder
- •Currently enrolled in a weight-loss or weight-management program
- •On a special or prescribed diet for other reasons (e.g., Celiac disease)
- •Currently taking any medication that is meant for, or has known effect on, appetite
- •Any history of surgical intervention for weight management
- •Abnormal screening labs (renal dysfunction (eGFR < 30 ml/min/1.73 m2), anemia, hypo- or hyperthyroidism, coagulopathy, abnormal liver function (AST, ALT > 3x upper limit of normal)
- •Local or systemic infectious disease with fever or requiring antibiotic within four weeks of screening visit
- •QTc interval above normal or the current use of any concomitant QT-prolonging drug
- •A clinically significant abnormal ECG
- •Current addiction to alcohol or substances of abuse
- •Unwillingness or language barriers precluding adequate understanding or cooperation
- •Use of systemic corticosteroids or other medication known to cause insulin resistance in previous six weeks prior to the screening visit and throughout the study
- •Diagnosis of bladder outlet obstruction or use of antimuscarinic medications for treatment of overactive bladder
- •Use of β-adrenergic receptor blockers or calcium channel blockers
- •Heart disease including Coronary Artery Disease (CAD), Congestive Heart Failure (CHF), or cardiac arrhythmias
- •Uncontrolled sever hypertension (Defined as systolic blood pressure ≥ 180 mm Hg and/or diastolic blood pressure ≥110 mm Hg)
- •Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent.
研究组 & 干预措施
Obese Group
Single dose, 100mg oral mirabegron in Obese Insulin Resistant adults
干预措施: Mirabegron (Drug)
Non-Obese Group
Single dose, 100mg oral mirabegron in Non-Obese adults
干预措施: Mirabegron (Drug)
结局指标
主要结局
Glycerol Measured Catecholamine Sensitivity
时间窗: 28 days (± 14 days)
The change from baseline in catecholamine sensitivity as measured by glycerol from adipose tissue lipolysis
ADRB3 gene expression
时间窗: 28 days (± 14 days)
The change from baseline in ADRB3 gene expression as measured by qPCR
ADRB3 protein levels
时间窗: 28 days (± 14 days)
The change from baseline in ADRB3 protein levels as measured by Western Blot
Free Fatty Acid measured Catecholamine Sensitivity
时间窗: 28 days (± 14 days)
The change from baseline in catecholamine sensitivity as measured by Free Fatty Acid from adipose tissue lipolysis
次要结局
- FGF-21 Adipokine Gene Expression(28 days (± 14 days))
- IL-6 Adipokine Gene Expression(28 days (± 14 days))
研究者
Vala Hamidi
Assistant Clinical Professor, University of California, San Diego
University of California, San Diego