Small Extracellular Vesicles and Insulin Action
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age25-55
SponsorWashington University School of Medicine
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
People with Metabolically Unhealthy Obesity - Low Calorie Diet
BehavioralConsumption of a low-calorie diet with caloric intake reduced by \~25% to achieve \~10% weight loss in about 4 to 5 months.
Treatment groups
72 Participants
are divided into 3 treatment groupsGroup A: Metabolically healthy lean - Baseline testing onlyNo intervention 0 interventions
Group B: People with Metabolically Healthy Obesity - Baseline testing onlyNo intervention 0 interventions
Group C: People with Metabolically Unhealthy Obesity - Low Calorie DietExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Baseline only (cross-sectional comparison of metabolically healthy lean, and of people with metabolically healthy or metabolically unhealthy obesity).2
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.
Time frame
Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesitySecondary outcomes
1
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.
Time frame
Baseline only (cross-sectional comparison of metabolically healthy lean, and of people with metabolically healthy or metabolically unhealthy obesity).2
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.
Time frame
Baseline only (cross-sectional comparison of metabolically healthy lean, and of people with metabolically healthy or metabolically unhealthy obesity).3
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.
Time frame
Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity4
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.
Time frame
Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesitySponsors and contacts
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Source ClinicalTrials.gov