ObesitySEVNCT05933707
Small Extracellular Vesicles and Insulin Action
A study testing People with Metabolically Unhealthy Obesity - Low Calorie Diet in people with Obesity and Insulin Resistance, run by Washington University School of Medicine at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 25 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Insulin Resistance, Metabolically Healthy Obesity
- What is being tested?
- People with Metabolically Unhealthy Obesity - Low Calorie Diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jun 2023to 31 Aug 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Kyle Timmons, 314-273-1879, nutritionresearch@wustl.edu
Beth Henk, 3143628250, bhenk@wustl.edu
About this study
Official title: Effect of Small Extracellular Vesicles From Adipose Tissue on Insulin Action
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.
Read the 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.
- Being tested
- People with Metabolically Unhealthy Obesity - Low Calorie Diet
- Keywords
- Obesity, Weight Loss, Exosomes, Extracellular vesicles
- Medical subject headings
- Obesity, Insulin Resistance, Obesity, Metabolically Benign, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
People with Metabolically Unhealthy Obesity - Low Calorie DietBehavioural
Also called Dietary weight loss
Consumption of a low-calorie diet with caloric intake reduced by ~25% to achieve ~10% weight loss in about 4 to 5 months.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Behavioral: People with Metabolically Unhealthy Obesity - Low Calorie Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Insulin sensitivity
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Change in insulin sensitivity
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Measured: Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Fat mass and fat free mass
Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Change in fat mass and fat free mass
Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA)
Measured: Before and after 10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Abdominal adipose tissue volumes
Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Change in abdominal adipose tissue volumes
Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Measured: Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Intra-hepatic triglyceride content
Intra-hepatic triglyceride content will be assessed by magnetic resonance techniques
Measured: Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Change in intra-hepatic triglyceride content
Intra-hepatic triglyceride content will be assessed by magnetic resonance techniques
Measured: Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2023
- Study start14 Jun 2023
- Primary completion1 Jun 2028 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dmitri Samovski, PhD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05933707
- Sponsor's protocol ID
- 202005117
- Acronym
- SEV
- Status last verified
- Jul 2026
- First submitted
- 27 Jun 2023
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Currently there is no plan to share individual participant data.
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Small Extracellular Vesicles From Adipose Tissue on Insulin Action
- ClinicalTrials.gov ID
- NCT05933707
- Acronym / sponsor ID
- SEV / 202005117
- Keywords
- Obesity, Weight Loss, Exosomes, Extracellular vesicles
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 14 Jun 2023 (actual)
- Primary completion
- 1 Jun 2028 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 6 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 | Behavioral: People with Metabolically Unhealthy Obesity - Low Calorie DietPeople 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. |
Who may qualify
- Ages
- 25 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| People with Metabolically Unhealthy Obesity - Low Calorie DietAlso: Dietary weight lossConsumption of a low-calorie diet with caloric intake reduced by ~25% to achieve ~10% weight loss in about 4 to 5 months. | Behavioural | People with Metabolically Unhealthy Obesity - Low Calorie Diet |
Primary outcome
Effect of exosomes on insulin sensitivity in cultured cells
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, and of people with metabolically healthy or metabolically unhealthy obesity).
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.
Change in the effect of exosomes on insulin sensitivity
Time frame: Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
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.
12 secondary outcomes
Differences in the content of microRNAs within exosomes obtained from plasma and adipose tissue
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Insulin sensitivity
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Change in insulin sensitivity
Time frame: Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Fat mass and fat free mass
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Change in fat mass and fat free mass
Time frame: Before and after 10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Abdominal adipose tissue volumes
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Change in abdominal adipose tissue volumes
Time frame: Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Intra-hepatic triglyceride content
Time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, and people with metabolically healthy or metabolically unhealthy obesity).
Change in intra-hepatic triglyceride content
Time frame: Before and after ~10% weight loss (~4-5 months) in people with metabolically abnormal obesity
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2026.
- Individual participant dataSharing planned: No. Currently there is no plan to share individual participant data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dmitri Samovski, PhD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing People with Metabolically Unhealthy Obesity - Low Calorie Diet in people with Obesity and Insulin Resistance, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kyle Timmons (3142731879, nutritionresearch@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of exosomes on insulin sensitivity in cultured cells (time frame: Baseline only (cross-sectional comparison of metabolically healthy lean, and of people with metabolically healthy or metabolically unhealthy obesity).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2026.