Active, not recruitingPhase 1Interventional
What this study is about
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.
A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.
Basic eligibility
Age18 Years to 70 Years
SexAll
Healthy volunteersAccepted
ConditionObesity, Prediabetes
Full registry criteria
Inclusion Criteria: * 1\. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Males and females 18-70 years old 4. 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 5. 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 Exclusion Criteria: * 1\. Diabetes, defined as fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%, or diagnosis of diabetes 2. Pregnancy or lactation 3. Currently taking therapeutic anticoagulation which might increase risk of bleeding from fat biopsy (e.g., warfarin, direct oral anticoagulants) 4. History of eating disorder 5. Currently enrolled in a weight-loss or weight-management program 6. On a special or prescribed diet for other reasons (e.g., Celiac disease) 7. Currently taking any medication that is meant for, or has known effect on, appetite 8. Any history of surgical intervention for weight management 9. 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) 10. Local or systemic infectious disease with fever or requiring antibiotic within four weeks of screening visit 11. QTc interval above normal or the current use of any concomitant QT-prolonging drug 12. A clinically significant abnormal ECG 13. Current addiction to alcohol or substances of abuse 14. Unwillingness or language barriers precluding adequate understanding or cooperation 15. 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 16. Diagnosis of bladder outlet obstruction or use of antimuscarinic medications for treatment of overactive bladder 17. Use of β-adrenergic receptor blockers or calcium channel blockers 18. Heart disease including Coronary Artery Disease (CAD), Congestive Heart Failure (CHF), or cardiac arrhythmias 19. Uncontrolled sever hypertension (Defined as systolic blood pressure ≥ 180 mm Hg and/or diastolic blood pressure ≥110 mm Hg) 20. 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.
Primary outcomes
ADRB3 gene expression28 days (± 14 days)The change from baseline in ADRB3 gene expression as measured by qPCR
ADRB3 protein levels28 days (± 14 days)The change from baseline in ADRB3 protein levels as measured by Western Blot
Glycerol Measured Catecholamine Sensitivity28 days (± 14 days)The change from baseline in catecholamine sensitivity as measured by glycerol from adipose tissue lipolysis
Free Fatty Acid measured Catecholamine Sensitivity28 days (± 14 days)The change from baseline in catecholamine sensitivity as measured by Free Fatty Acid from adipose tissue lipolysis