Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05933707
Other study ID # 202005117
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date June 14, 2023
Est. completion date December 2028

Study information

Verified date July 2023
Source Washington University School of Medicine
Contact Johanna Sonnenschein
Phone 3142731879
Email nutritionresearch@wustl.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 72
Est. completion date December 2028
Est. primary completion date October 2028
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 25 Years to 55 Years
Eligibility 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

Study Design


Intervention

Behavioral:
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.

Locations

Country Name City State
United States Washington University School of Medicine Saint Louis Missouri

Sponsors (1)

Lead Sponsor Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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).
Primary 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 Differences in the content of microRNAs within exosomes obtained from plasma and adipose tissue Exosomes obtained from the plasma and adipose tissue of metabolically healthy lean participants, and participants with metabolically healthy or metabolically unhealthy obesity will be analyzed to determine their microRNA composition. Baseline only (cross-sectional comparison of metabolically healthy lean, and of people with metabolically healthy or metabolically unhealthy obesity).
Secondary Differences in the content of lipids within exosomes obtained from plasma and adipose tissue Exosomes obtained from the plasma and adipose tissue of metabolically healthy lean participants, and participants with metabolically healthy or metabolically unhealthy obesity will be analyzed to determine their lipid composition. Baseline only (cross-sectional comparison of metabolically healthy lean, and of people with metabolically healthy or metabolically unhealthy obesity).
Secondary Changes in the content of microRNAs within exosomes obtained from plasma and adipose tissue Exosomes obtained from the plasma and adipose tissue of metabolically unhealthy obesity before and after weight loss will be analyzed to determine changes in their microRNA content after weight loss. Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Secondary Changes in the content of lipids within exosomes obtained from plasma and adipose tissue Exosomes obtained from the plasma and adipose tissue of metabolically unhealthy obesity before and after weight loss will be analyzed to determine changes in their lipid content after weight loss. Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Secondary Insulin sensitivity Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Secondary Change in insulin sensitivity Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Secondary Fat mass and fat free mass Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA) Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Secondary Change in fat mass and fat free mass Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA) Before and after 10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Secondary Abdominal adipose tissue volumes Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI) Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Secondary Change in abdominal adipose tissue volumes Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI) Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Secondary Intra-hepatic triglyceride content Intra-hepatic triglyceride content will be assessed by magnetic resonance techniques Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Secondary Change in intra-hepatic triglyceride content Intra-hepatic triglyceride content will be assessed by magnetic resonance techniques Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
See also
  Status Clinical Trial Phase
Recruiting NCT04101669 - EndoBarrier System Pivotal Trial(Rev E v2) N/A
Recruiting NCT04243317 - Feasibility of a Sleep Improvement Intervention for Weight Loss and Its Maintenance in Sleep Impaired Obese Adults N/A
Terminated NCT03772886 - Reducing Cesarean Delivery Rate in Obese Patients Using the Peanut Ball N/A
Completed NCT03640442 - Modified Ramped Position for Intubation of Obese Females. N/A
Completed NCT04506996 - Monday-Focused Tailored Rapid Interactive Mobile Messaging for Weight Management 2 N/A
Recruiting NCT06019832 - Analysis of Stem and Non-Stem Tibial Component N/A
Active, not recruiting NCT05891834 - Study of INV-202 in Patients With Obesity and Metabolic Syndrome Phase 2
Active, not recruiting NCT05275959 - Beijing (Peking)---Myopia and Obesity Comorbidity Intervention (BMOCI) N/A
Recruiting NCT04575194 - Study of the Cardiometabolic Effects of Obesity Pharmacotherapy Phase 4
Completed NCT04513769 - Nutritious Eating With Soul at Rare Variety Cafe N/A
Withdrawn NCT03042897 - Exercise and Diet Intervention in Promoting Weight Loss in Obese Patients With Stage I Endometrial Cancer N/A
Completed NCT03644524 - Heat Therapy and Cardiometabolic Health in Obese Women N/A
Recruiting NCT05917873 - Metabolic Effects of Four-week Lactate-ketone Ester Supplementation N/A
Active, not recruiting NCT04353258 - Research Intervention to Support Healthy Eating and Exercise N/A
Completed NCT04507867 - Effect of a NSS to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III N/A
Recruiting NCT03227575 - Effects of Brisk Walking and Regular Intensity Exercise Interventions on Glycemic Control N/A
Completed NCT01870947 - Assisted Exercise in Obese Endometrial Cancer Patients N/A
Recruiting NCT05972564 - The Effect of SGLT2 Inhibition on Adipose Inflammation and Endothelial Function Phase 1/Phase 2
Recruiting NCT06007404 - Understanding Metabolism and Inflammation Risks for Diabetes in Adolescents
Recruiting NCT05371496 - Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction Phase 2