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ADRB3 Signaling Pathway in Human Adipose Tissue

Primary Purpose

Obesity, Prediabetes

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Mirabegron
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Obesity, Prediabetes

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • UC San Diego Altman Clinical & Translational Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Obese Group

Non-Obese Group

Arm Description

Single dose, 100mg oral mirabegron in Obese Insulin Resistant adults

Single dose, 100mg oral mirabegron in Non-Obese adults

Outcomes

Primary Outcome Measures

ADRB3 gene expression
The change from baseline in ADRB3 gene expression as measured by qPCR
ADRB3 protein levels
The change from baseline in ADRB3 protein levels as measured by Western Blot
Glycerol Measured Catecholamine Sensitivity
The change from baseline in catecholamine sensitivity as measured by glycerol from adipose tissue lipolysis
Free Fatty Acid measured Catecholamine Sensitivity
The change from baseline in catecholamine sensitivity as measured by Free Fatty Acid from adipose tissue lipolysis

Secondary Outcome Measures

FGF-21 Adipokine Gene Expression
The change from baseline in FGF-21 gene expression as measured by qPCR
IL-6 Adipokine Gene Expression
The change from baseline in IL-6 gene expression as measured by qPCR

Full Information

First Posted
November 21, 2022
Last Updated
July 20, 2023
Sponsor
University of California, San Diego
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1. Study Identification

Unique Protocol Identification Number
NCT05634174
Brief Title
ADRB3 Signaling Pathway in Human Adipose Tissue
Official Title
Identifying Responsible Signaling Pathway for Adrenergic Beta-3 Receptor Regulation in Human Subcutaneous White Adipose Tissue
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 1, 2023 (Anticipated)
Primary Completion Date
September 30, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Prediabetes

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Obese Group
Arm Type
Experimental
Arm Description
Single dose, 100mg oral mirabegron in Obese Insulin Resistant adults
Arm Title
Non-Obese Group
Arm Type
Experimental
Arm Description
Single dose, 100mg oral mirabegron in Non-Obese adults
Intervention Type
Drug
Intervention Name(s)
Mirabegron
Other Intervention Name(s)
Myrbetriq
Intervention Description
Single dose, 100mg oral mirabegron
Primary Outcome Measure Information:
Title
ADRB3 gene expression
Description
The change from baseline in ADRB3 gene expression as measured by qPCR
Time Frame
28 days (± 14 days)
Title
ADRB3 protein levels
Description
The change from baseline in ADRB3 protein levels as measured by Western Blot
Time Frame
28 days (± 14 days)
Title
Glycerol Measured Catecholamine Sensitivity
Description
The change from baseline in catecholamine sensitivity as measured by glycerol from adipose tissue lipolysis
Time Frame
28 days (± 14 days)
Title
Free Fatty Acid measured Catecholamine Sensitivity
Description
The change from baseline in catecholamine sensitivity as measured by Free Fatty Acid from adipose tissue lipolysis
Time Frame
28 days (± 14 days)
Secondary Outcome Measure Information:
Title
FGF-21 Adipokine Gene Expression
Description
The change from baseline in FGF-21 gene expression as measured by qPCR
Time Frame
28 days (± 14 days)
Title
IL-6 Adipokine Gene Expression
Description
The change from baseline in IL-6 gene expression as measured by qPCR
Time Frame
28 days (± 14 days)
Other Pre-specified Outcome Measures:
Title
ADRB3 Signaling Pathway
Description
Identification of ADRB3 signaling pathway as measured by RNA sequencing of adipocytes
Time Frame
28 days (± 14 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Todd May
Phone
858-246-2169
Email
tmay@ucsd.edu
Facility Information:
Facility Name
UC San Diego Altman Clinical & Translational Research Institute
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Todd May
Email
tmay@ucsd.ed

12. IPD Sharing Statement

Plan to Share IPD
No

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ADRB3 Signaling Pathway in Human Adipose Tissue

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