Small Extracellular Vesicles and Insulin Action

NCT05933707 | Recruiting DMC

• 1 other identifier: 202005117
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Obesity; Weight Loss; Exosomes; Extracellular vesicles

Outcome Measures

Primary Outcomes (2)

• Effect of exosomes on insulin sensitivity in cultured cells

  Exosomes obtained from the plasma and adipose tissue of metabolically healthy lean participants, and participants with metabolically healthy or metabolically unhealthy obesity will be tested in cultured cells and mice to determine their effect on insulin sensitivity.

  Baseline only (cross-sectional comparison of metabolically healthy lean, and of people with metabolically healthy or metabolically unhealthy obesity).

• Change in the effect of exosomes on insulin sensitivity

  Exosomes obtained from the plasma and adipose tissue of participants with metabolically unhealthy obesity before and after 10% weight loss will be tested in cultured cells and mice to determine their effect on insulin sensitivity.

  Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity

Secondary Outcomes (12)

• Differences in the content of microRNAs within exosomes obtained from plasma and adipose tissue

  Baseline only (cross-sectional comparison of metabolically healthy lean, and of people with metabolically healthy or metabolically unhealthy obesity).

• Differences in the content of lipids within exosomes obtained from plasma and adipose tissue

  Baseline only (cross-sectional comparison of metabolically healthy lean, and of people with metabolically healthy or metabolically unhealthy obesity).

• Changes in the content of microRNAs within exosomes obtained from plasma and adipose tissue

  Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity

• Changes in the content of lipids within exosomes obtained from plasma and adipose tissue

  Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity

• Insulin sensitivity

  Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).

Study Arms (3)

Metabolically healthy lean - Baseline testing only

NO INTERVENTION

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.

People with Metabolically Healthy Obesity - Baseline testing only

NO INTERVENTION

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.

People with Metabolically Unhealthy Obesity - Low Calorie Diet

EXPERIMENTAL

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.

Behavioral: People with Metabolically Unhealthy Obesity - Low Calorie Diet

Interventions

People with Metabolically Unhealthy Obesity - Low Calorie Diet BEHAVIORAL

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

Also known as: Dietary weight loss

People with Metabolically Unhealthy Obesity - Low Calorie Diet

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

MeSH Terms

Conditions

Obesity; Insulin Resistance; Obesity, Metabolically Benign; Weight Loss

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Body Weight Changes

Study Officials

• Dmitri Samovski, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kyle Timmons

CONTACT

3142731879; nutritionresearch@wustl.edu

Beth Henk

CONTACT

3143628250; bhenk@wustl.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2023
• First Posted: July 6, 2023
• Study Start: June 8, 2023
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)