Small Extracellular Vesicles and Insulin Action

NCT ID: NCT05933707

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-08
• Study Completion Date: 2029-09-01

Brief Summary

The goals of this research study are to: 1) understand why some people with obesity are protected from developing conditions such as type 2 diabetes and cardiovascular disease while others are more likely to develop obesity-related conditions; 2) assess the effect of small extracellular vesicles (sEVs also called exosomes), obtained from human participants, on metabolic function in cultured cells and in mice.

Detailed Description

Insulin resistance is commonly associated with obesity and is a major contributor to the development of obesity-related metabolic diseases, including nonalcoholic fatty liver disease, the metabolic syndrome, and type 2 diabetes (T2D). Most persons with obesity are "metabolically unhealthy" (MUO), often defined by having insulin resistance and the metabolic syndrome. However, a subset of people with obesity are metabolically healthy (MHO) and protected from the adverse metabolic effects of excess adiposity. The mechanisms that determine the differences in metabolic health between people with MUO and MHO are not unclear. This project will examine the effects of plasma and adipose tissue small extracellular vesicles (sEVs) on multi-organ insulin action. The investigators will isolate sEVs from subcutaneous abdominal adipose tissue biopsies and blood samples obtained from human participants with MHO, MUO or who are metabolically healthy and lean (MHL) and examine the effects of these sEVs on insulin resistance in muscle, liver and fat cells in culture and on multi-organ insulin sensitivity in lean and obese mice. The investigators will also identify differences in the potential bioactive molecules, namely miRNA and bioactive lipids, that are carried by sEVs. The results from this study will help determine whether plasma or adipose tissue sEVs in people who are MHL, MHO, or MUO are involved in regulating liver, muscle and adipose tissue insulin sensitivity. These results could identify novel pathways that regulate metabolic health in people and provide the foundation for exploring the potential of sEVs as a therapeutic target to prevent and treat the metabolic complications of obesity.

Conditions

Obesity; Insulin Resistance; Metabolically Healthy Obesity; Obesity, Metabolically Benign

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Metabolically healthy lean - Baseline testing only

Metabolically healthy lean - Lean individuals that have good glucose (sugar) control (defined as normal fasting glucose, glucose tolerance and hemoglobin A1c), normal insulin sensitivity (defined as Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] <2.5) and normal intrahepatic triglyceride (fat) levels.

Dietary intervention - None.

Group Type: NO_INTERVENTION

No interventions assigned to this group

People with Metabolically Healthy Obesity - Baseline testing only

People with Metabolically Healthy Obesity - Persons with obesity that have good glucose (sugar) control, normal insulin sensitivity and normal intrahepatic triglyceride (fat) levels.

Dietary intervention - None.

Group Type: NO_INTERVENTION

No interventions assigned to this group

People with Metabolically Unhealthy Obesity - Low Calorie Diet

People with Metabolically Unhealthy Obesity - Persons with obesity with plasma glucose and intrahepatic triglyceride (fat) levels higher than recommended in combination with insulin resistance (defined as HOMA-IR ≥2.5).

Dietary intervention - Low calorie diet.

Group Type: EXPERIMENTAL

People with Metabolically Unhealthy Obesity - Low Calorie Diet

Intervention Type: BEHAVIORAL

Consumption of a low-calorie diet with caloric intake reduced by \~25% to achieve \~10% weight loss in about 4 to 5 months.

Interventions

People with Metabolically Unhealthy Obesity - Low Calorie Diet

Consumption of a low-calorie diet with caloric intake reduced by \~25% to achieve \~10% weight loss in about 4 to 5 months.

Intervention Type: BEHAVIORAL

Other Intervention Names

Dietary weight loss

Eligibility Criteria

Inclusion Criteria

• Metabolically healthy lean subjects must have a BMI ≥18.5 and ≤24.9 kg/m²; Subjects with obesity must have a BMI ≥30.0 and ≤50.0 kg/m²
• Metabolically healthy lean and people with metabolically healthy obesity must have intrahepatic triglyceride (IHTG) content ≤5%; fasting plasma glucose concentration <100 mg/dl, 2-hr oral glucose tolerance plasma glucose concentration <140 mg/dl, hemoglobin A 1C (HbA1c) ≤5.6% and HOMA-IR <2.5.
• People with metabolically unhealthy obesity must have intrahepatic triglyceride (IHTG) content ≥5.6%; HOMA-IR ≥2.5, and HbA1c 5.7%-6.4%, or fasting plasma glucose concentration ≥100 mg/dl, or 2-hr oral glucose tolerance test (OGTT) plasma glucose concentration ≥140 mg/dl.

Exclusion Criteria

• History of diabetes, liver disease other than NAFLD or other serious diseases,
• Consume excessive amounts of alcohol (>21 units/week for men and >14 units/week for women),
• Take medications that could affect the study outcome measures, engage in regular exercise (>120 min/week),
• Are pregnant or lactating

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dmitri Samovski, PhD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kyle Timmons

Role: CONTACT

nutritionresearch@wustl.edu

3142731879

Beth Henk

Role: CONTACT

bhenk@wustl.edu

3143628250

Facility Contacts

Johanna Sonnenschein

Role: primary

nutritionresearch@wustl.edu

3142731879

Beth Henk

Role: backup

bhenk@wustl.edu

3143628250

Other Identifiers

202005117

Identifier Type: -

Identifier Source: org_study_id