Harnessing Macrophage Lysosomal Lipid Metabolism in Obesity

Healthy Clinical Trial

— ATM  

Official title:

Harnessing Macrophage Lysosomal Lipid Metabolism in Obesity-Associated Diseases

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06335771
• Other study ID #: 2098077
• Secondary ID: R01DK131188
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 2024
• Est. completion date: March 2028

Study information

• Verified date: May 2024
• Source: University of Missouri-Columbia
• Contact: Heather McHatton
• Phone: (573) 882-7619
• Email: heathermchatton[@]health.missouri.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to evaluate the role of transcription factor EB (TFEB) in adipose (fat) tissue macrophages (ATM) in regulating adipose tissue and systemic metabolic function in obesity. The investigators will assess the differences in ATM lipid metabolism in people with metabolically abnormal obesity and lean individuals. Both groups will have: - screening visit - imaging (body composition testing - dual-energy x-ray absorptiometry (DEXA) scans, magnetic resonance imaging [MRI] and magnetic resonance spectroscopy [MRS] scans) - Overnight visit with intravenous infusion (IV), muscle, and fat tissue biopsies Participants with obesity will complete meetings with study team members for a weight loss intervention to achieve a 10% body weight loss.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: March 2028
• Est. primary completion date: March 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria :

• age: =18 but =70 years
• not pregnant or breastfeeding
• weight stable and sedentary before enrollment
• no use tobacco products, excessive amounts of alcohol, or dietary supplements, or medications known to or suspected to affect glucose and lipid metabolism (aside from certain medications used to treat diabetes in the metabolically abnormal obesity [MAO]-Type 2 Diabetes group)
• no evidence of significant organ system dysfunction or disease (e.g. chronic severe kidney disease, cancer)
• participants must fulfil all of the following group-specific inclusion criteria below:

Lean group:

• Body mass index (BMI) =18.5 but <25.0 kg/m2
• Intrahepatic triglyceride (IHTG) content <5%
• fasting blood glucose concentration: <100 mg/dl
• blood glucose concentration 2 h after a 75 g oral glucose challenge: <140 mg/dl
• Hemoglobin A1C (HbA1c) <5.7 %

Metabolically normal obesity (MNO) group:

• BMI =30.0 but <45.0 kg/m2
• IHTG content <5%
• fasting blood glucose concentration: <100 mg/dl
• blood glucose concentration 2 h after a 75 g oral glucose challenge: <140 mg/dl
• HbA1c <5.7 % Metabolically abnormal obesity (MAO)-insulin resistance and non-alcoholic fatty liver

disease (NAFLD) group:

• BMI =30.0 but <45.0 kg/m2
• IHTG content >7.5%
• fasting blood glucose concentration: =100 but <126 mg/dl
• blood glucose concentration 2 h after a 75 g oral glucose challenge: =140 but <200 mg/dl
• HbA1c: =5.7 but <6.4 %

MAO-type 2 diabetes group:

• BMI =30.0 but <45.0 kg/m2
• clinical diagnosis of type 2 diabetes or fasting blood glucose concentration >126 mg/dl or blood glucose concentration 2 h after a 75 g oral glucose challenge>200 mg/dl or HbA1c >6.4 % without medication if not diagnosed and medically treated for diabetes

Exclusion Criteria:

• Individuals that do not meet all inclusion Criterion

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Diabetes Type 2
• Fatty Liver
• Healthy
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver
• Obesity

Intervention

Other:
• Dietary consultation weight loss intervention
Participants will meet with a member of the study team biweekly for about 6 months.

Locations

Country	Name	City	State
United States	University of Missouri School of Medicine	Columbia	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Bettina Mittendorfer	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin sensitivity assessed as insulin-mediated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure.		up to 6 months after the intervention
Primary	24-hour plasma glucose concentration		up to 6 months after the intervention
Primary	Macrophage isolation in adipose tissue biopsy	macrophage gene expression using RNA sequencing and fluorescent activated cell sorting (FACS)	up to 6 months after the intervention
Primary	Macrophage isolation in skeletal muscle tissue	macrophage gene expression using RNA sequencing and fluorescent activated cell sorting (FACS)	up to 6 months after the intervention