ObesityNCT02706262

Complex Effects of Dietary Manipulation on Metabolic Function, Inflammation and Health

A study testing Metabolically abnormal obese - Mediterranean diet, Metabolically abnormal obese - Low carbohydrate ketogenic diet and Metabolically abnormal obese - Plant-based, very-low-fat diet in people with Obesity and Insulin Resistance, run by Washington University School of Medicine at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

The purpose of this research study is to 1) understand how some, but not all people with obesity develop obesity related conditions such as type 2 diabetes and cardiovascular disease, and 2) compare the effects of 3 popular weight loss diets (Mediterranean, low-carbohydrate, or a very-low-fat plant-based diet) in… Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Obesity, Insulin Resistance
What is being tested?: Metabolically abnormal obese - Mediterranean diet, Metabolically abnormal obese - Low carbohydrate ketogenic diet and Metabolically abnormal obese - Plant-based, very-low-fat diet
Type of treatment: Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 180 participants
Where: 1 siteUnited States
Study dates: Feb 2016to Dec 2027
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 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Metabolically normal lean subjects must have a BMI ≥18.5 and ≤24.9 kg/m2; Obese subjects must have a BMI ≥30.0 and ≤50.0 kg/m2
Metabolically normal lean and obese subjects must have intrahepatic triglyceride (IHTG) content ≤5%; plasma triglyceride (TG) concentration <150 mg/dl; fasting plasma glucose concentration <100 mg/dl, 2-hr oral glucose tolerance plasma glucose concentration <140 mg/dl, and hemoglobin A1C ≤5.6%
Metabolically abnormal obese subjects must have intrahepatic triglyceride (IHTG) content ≥5.6%; HbA1C ≥5.7%, 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

Medical, surgical, or biological menopause
Previous bariatric surgery where the gastrointestinal tract is reconstructed such as Roux-en-Y, sleeve gastrectomy and biliopancreatic diversion surgeries
Laparoscopic adjustable gastric band (lab band) surgery within the last 3 years
Structured exercise ≥250 min per week (e.g., brisk walking)
Unstable weight (>4% change during the last 2 months before entering the study)
Significant organ system dysfunction (e.g., diabetes requiring medications, severe pulmonary, kidney or cardiovascular disease)

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Polycystic ovary syndrome
Cancer or cancer that has been in remission for <5 years
Major psychiatric illness
Conditions that render subject unable to complete all testing procedures (e.g., severe ambulatory impairments, limb amputations, or metal implants that interfere with imaging procedures; coagulation disorders)
Use of medications that are known to affect the study outcome measures (e.g., steroids, non-statin lipid-lowering medications) or increase the risk of study procedures (e.g., anticoagulants) and that cannot be temporarily discontinued for this study
Use of antibiotics in last 60 days
Smoke cigarettes > 10 cigarettes/week
Use marijuana >2 x/week, or use of illegal drugs
Men who consume >21 units (e.g. glass of wine or bottle of beer) of alcohol per week and women who consume >14 units of alcohol per week
Pregnant or lactating women
Vegans, vegetarians, those with lactose intolerance and/or severe aversions/sensitivities to eggs, fish, nuts, wheat and soy, and/or any individuals with food allergies that induce an anaphylactic response
Persons who are not able to grant voluntary informed consent
Persons who are unable or unwilling to follow the study protocol or who, for any reason, the research team considers not an appropriate candidate for this study, including non-compliance with screening appointments or study visits

Trial locations and contacts

1 site in 1 country.

United States1 site

Washington University School of Medicine
St Louis, Missouri, 63110

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About this study

Read the detailed description

Obesity is associated with a constellation of cardiometabolic abnormalities (including insulin resistance, elevated blood pressure and dyslipidemia) that are risk factors for diabetes and cardiovascular disease. However, not all people experience the typical "complications" associated with obesity. Approximately 25% of obese people are protected from the adverse metabolic effects of excess fat accumulation and are considered metabolically-normal, based on their normal response to insulin. The mechanisms responsible for the development of insulin resistance and cardiometabolic complications in some, but not all, obese persons are unknown.

In people that do develop the typical "complications" associated with obesity weight loss has profound therapeutic effects. Currently, there are three distinctly different types of diets that have demonstrated considerable benefits in improving cardiometabolic health in both lean and obese people: 1) a Mediterranean diet, 2) a low-carbohydrate, ketogenic diet, and 3) a plant-based, very-low-fat diet. However, there is considerable inter-individual variability in body weight loss among people in response to any given diet, and it is not known why some people lose more weight with one diet than another. The mechanisms responsible for the different weight and metabolic responses to specific types of diets and the independent effects of weight loss and dietary macronutrient composition on cardiometabolic health are unclear.

The overarching goal of this project is therefore to fill these gaps in knowledge by conducting a careful cross-sectional characterization of metabolically normal lean, metabolically normal obese and metabolically abnormal obese individuals to compare body composition, body fat distribution, the plasma metabolome, systemic and adipose tissue inflammation and immune system function, adipose tissue and muscle biological function, the gut microbiome, the brain's structure, cognitive function and central reward mechanisms, and taste sensation between groups. . Metabolically abnormal obese participants will then be randomized to follow a Mediterranean, a low-carbohydrate ketogenic or a plant-based, very-low-fat diet to examine the different effects of these diets on the above outcomes with the purpose to determine the beneficial or potentially harmful effects of these different diets.

Conditions: Obesity, Insulin Resistance
Being tested: Metabolically abnormal obese - Mediterranean diet, Metabolically abnormal obese - Low carbohydrate ketogenic diet, Metabolically abnormal obese - Plant-based, very-low-fat diet, Annual Follow-up Visits
Medical subject headings: Obesity, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Metabolically abnormal obese - Mediterranean dietOther
The effect of consuming a Mediterranean diet will be examined over 3 different phases: (i) weight maintenance for 4 to 8 weeks, with all meals provided; (ii) controlled 7-10% weight loss with caloric intake reduced by 25% to achieve the desired amount of weight loss in about 4 to 5 months with all meals provided; and (iii) Independent weight loss for about 4 months. During the independent weight loss phase of the study subjects will be asked to continue to consume a Mediterranean diet but will prepare all their food at home. No food will be provided during this portion of the study.
Metabolically abnormal obese - Low carbohydrate ketogenic dietOther
The effect of consuming a low-carbohydrate, ketogenic diet will be examined over 3 different phases: (i) weight maintenance for 4 to 8 weeks, with all meals provided; (ii) controlled 7-10% weight loss with caloric intake reduced by 25% to achieve the desired amount of weight loss in about 4 to 5 months with all meals provided; and (iii) Independent weight loss for about 4 months. During the independent weight loss phase of the study subjects will be asked to continue to consume a low carbohydrate ketogenic diet but will prepare all their food at home. No food will be provided during this portion of the study.
Metabolically abnormal obese - Plant-based, very-low-fat dietOther
The effect of consuming a plant-based, very-low-fat diet will be examined over 3 different phases: (i) weight maintenance for 4 to 8 weeks, with all meals provided; (ii) controlled 7-10% weight loss with caloric intake reduced by 25% to achieve the desired amount of weight loss in about 4 to 5 months with all meals provided; and (iii) Independent weight loss for about 4 months. During the independent weight loss phase of the study subjects will be asked to continue to consume a plant-based, very-low-fat diet but will prepare all their food at home. No food will be provided during this portion of the study.
Annual Follow-up VisitsBehavioural
Metabolic health will be assessed 1 and 2-years after competing the diet intervention study. No intervention will be performed during the time.

Study groups in NCT02706262
Study group	Role	What they receive
Metabolically normal lean - Baseline testing only	No intervention	Metabolically normal lean - Lean individuals that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content. Dietary intervention - None.
Metabolically normal obese - Baseline testing only	No intervention	Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content. Dietary intervention - None.
Metabolically abnormal obese - Mediterranean diet	Experimental	Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver. Dietary intervention - A nutritionally balanced diet that includes fruits, vegetables, fish, beans, whole grains, and olive oil with approximately 50% of daily calories coming from complex carbohydrates, 30% of calories from fat, and 20% of calories from protein. Receives: Other: Metabolically abnormal obese - Mediterranean diet; Behavioral: Annual Follow-up Visits
Metabolically abnormal obese - Low carbohydrate ketogenic diet	Experimental	Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver. Dietary intervention - A very-low-carbohydrate, adequate protein, high-fat diet containing 20 grams of carbohydrate or less per day (about 5% of calories), derived mainly from vegetables. Receives: Other: Metabolically abnormal obese - Low carbohydrate ketogenic diet; Behavioral: Annual Follow-up Visits
Metabolically abnormal obese - Plant-based very-low-fat diet	Experimental	Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver. Dietary intervention - A plant-based diet high in complex carbohydrates and low in fat, protein, and sodium, with approximately 70% of daily calories from carbohydrates, 15% from fat, and 15% from protein. Receives: Other: Metabolically abnormal obese - Plant-based, very-low-fat diet; Behavioral: Annual Follow-up Visits

What is being measured

The primary outcome is the main question the study is designed to answer.

Insulin sensitivity
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in insulin sensitivity
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Measured: Before and after 4 to 8-weeks of weight maintenance and after 7-10% weight loss (~6-7 months)

Secondary outcomes (59)

24-hour glucose concentrations
Glucose concentrations will be evaluated from frequent blood samples over a 24 h period
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in 24-hour glucose concentrations
Glucose concentrations will be evaluated from frequent blood samples over a 24 h period
Measured: Before and after 4 to 8-weeks of weight maintenance and after 7-10% weight loss (~6-7 months)
24-hour hormone concentrations
Plasma hormone concentrations will be evaluated from frequent blood sampling over a 24 h period
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in 24-hour hormone concentrations
Plasma hormone concentrations will be evaluated from frequent blood sampling over a 24 h period
Measured: Before and after 4 to 8-weeks of weight maintenance and after 7-10% weight loss (~6-7 months)
24-hour cytokine concentrations
Plasma cytokine concentrations will be evaluated from frequent blood sampling over a 24 h period
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
β-cell function
β-cell function will be assessed from a modified oral glucose tolerance test
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in β-cell function
β-cell function will be assessed from a modified oral glucose tolerance test
Measured: Before and after 7-10% weight loss (~6-7 months) and independent weight loss (12 months) in metabolically abnormal obese individuals only.
Insulin clearance
Insulin clearance will be assessed from a modified oral glucose tolerance test and hyperinsulinemic-euglycemic clamp procedure
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Insulin clearance
Insulin clearance will be assessed from a modified oral glucose tolerance test and hyperinsulinemic-euglycemic clamp procedure
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only.
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 normal lean, metabolically normal obese and metabolically abnormal obese subjects).
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 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
Exosome-mediated intercellular signaling
Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in exosome-mediated intercellular signaling
Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue
Measured: Before and after 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
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 normal lean, metabolically normal obese and metabolically abnormal obese subjects).
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 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
Leg adipose tissue volumes
Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in leg adipose tissue volumes
Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)
Measured: Before and after 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
Intra-hepatic triglyceride content
Intra-hepatic triglyceride content will be assessed by magnetic resonance techniques
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in intra-hepatic triglyceride content
Intra-hepatic triglyceride content will be assessed by magnetic resonance techniques
Measured: Before and after 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
Gut microbiome
Gut microbiota, meta-transcriptome (bacterial RNA sequencing to determine what proteins can be made by the microbiota) and the meta-metabolome (metabolites made by the microbiota) will be assessed
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in gut microbiome
Gut microbiota, meta-transcriptome (bacterial RNA sequencing to determine what proteins can be made by the microbiota) and the meta-metabolome (metabolites made by the microbiota) will be assessed
Measured: Before and during 4 to 8-weeks of weight maintenance, 7-10% weight loss (~6-7 months) and independent weight loss (12 months)
Plasma lipid profile
Fasting plasma lipid profile will be assessed by nuclear magnetic resonance (NMR) techniques
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in plasma lipid profile
Fasting plasma lipid profile will be assessed by nuclear magnetic resonance (NMR) techniques
Measured: Before and after 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
Aerobic fitness
Maximal oxygen consumption will be assessed using indirect calorimetry during a graded exercise test to volitional fatigue
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in aerobic fitness
Maximal oxygen consumption will be assessed using indirect calorimetry during a graded exercise test to volitional fatigue
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals randomized to the plant-based very-low-fat diet only
Carotid artery intima media thickness
Carotid artery intima media thickness will be assessed by ultrasound imaging
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in carotid artery intima media thickness
Carotid artery intima media thickness will be assessed by ultrasound imaging
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Cardiac structure and function
Ultrasound techniques will be used to assess cardiac structure and function
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in cardiac structure and function
Ultrasound techniques will be used to assess cardiac structure and function
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Endothelial function
Endothelial function will be assessed using a non-invasive device (EndoPat 2000) in response to reactive hyperemia.
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in endothelial function
Endothelial function will be assessed using a non-invasive device (EndoPat 2000) in response to reactive hyperemia.
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Arterial stiffness
Arterial stiffness will be assessed using a non-invasive device (SphygmoCor)
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in arterial stiffness
Arterial stiffness will be assessed using a non-invasive device (SphygmoCor)
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Physical activity
Physical activity will be assessed using tri-axial accelerometry
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in physical activity
Physical activity will be assessed using tri-axial accelerometry
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Sleep efficiency
Sleep efficiency will be assessed using tri-axial accelerometry
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in sleep efficiency
Sleep efficiency will be assessed using tri-axial accelerometry
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Rate of incorporation of 2H2O into lipids
Metabolic pathways relating to lipid (fat) synthesis in the liver and adipose tissue (fat) will be assessed by heavy water (2H2O) ingestion followed by fat biopsies and blood sampling
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in the rate of incorporation of 2H2O into lipids
Metabolic pathways relating to lipid (fat) synthesis in the liver and adipose tissue (fat) will be assessed by heavy water (2H2O) ingestion followed by fat biopsies and blood sampling
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Rate of incorporation of 2H2O into proteins
Metabolic pathways relating to protein synthesis in the muscle and adipose tissue will be assessed by heavy water (2H2O) ingestion followed by skeletal muscle and and adipose tissue biopsies and blood sampling
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in the rate of incorporation of 2H2O into proteins
Metabolic pathways relating to protein synthesis in the muscle and adipose tissue will be assessed by heavy water (2H2O) ingestion followed by skeletal muscle and and adipose tissue biopsies and blood sampling
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Taste intensity
Subjects will be evaluated by using the NIH toolbox Taste Intensity Test
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in taste intensity
Subjects will be evaluated by using the NIH toolbox Taste Intensity Test
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Sweet taste palatability
Sweet palatability will be assessed using the general Labeled Magnitude Scale
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in sweet taste palatability
Sweet palatability will be assessed using the general Labeled Magnitude Scale
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Immune function
Immune cell populations within plasma and adipose tissue will be profiled using multi-color fluorescence activated cell sorting (FACS) techniques.
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in immune function
Immune cell populations within plasma and adipose tissue will be profiled using multi-color fluorescence activated cell sorting (FACS) techniques.
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Food consumption-induced changes in brain blood flow
Food consumption-induced changes in brain blood flow will be assessed by blood-oxygen dependent (BOLD) and arterial spin labeling using functional magnetic resonance imaging (fMRI) techniques
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in food consumption-induced changes in brain blood flow
Food consumption-induced changes in brain blood flow will be assessed by blood-oxygen dependent (BOLD) and arterial spin labeling using functional magnetic resonance imaging (fMRI) techniques
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Transcriptome in blood, muscle and adipose tissue
The transcriptome (all RNA that are responsible for making proteins from DNA templates) will be evaluated by using RNA sequencing techniques
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in transcriptome in blood, muscle and adipose tissue
The transcriptome (all RNA that are responsible for making proteins from DNA templates) will be evaluated by using RNA sequencing techniques
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Epigenome in blood, muscle and adipose tissue
The epigenome (chemical modifications of DNA that signal genes to be on or off) will be evaluated by using Illumina Infinium HumanMethylation450 BeadChip assays.
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in epigenome in blood, muscle and adipose tissue
The epigenome (chemical modifications of DNA that signal genes to be on or off) will be evaluated by using Illumina Infinium HumanMethylation450 BeadChip assays.
Measured: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Dopamine receptor binding potential
Dopamine receptor binding potential will be assessed by Positron Emission Tomography (PET) using [11C]raclopride in the fasted and fed states
Measured: Baseline in fasted and fed states in metabolically abnormal obese participants only.
Subcutaneous abdominal adipose tissue oxygen tension
Oxygen tension will be assessed in subcutaneous abdominal adipose tissue in the abdomen using oxygen-sensitive fiber-optic probes (OxyLiteTM, Oxford Optronix, Ltd)
Measured: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in β-cell function
β-cell function will be assessed from a modified oral glucose tolerance test
Measured: Before and at annual follow-up visits (assessed up to 2 years) in metabolically abnormal obese individuals only.
Insulin clearance
Insulin clearance will be assessed from a modified oral glucose tolerance test
Measured: Before and at annual follow-up visits (assessed up to 2 years) in metabolically abnormal obese individuals only.
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 at annual follow-up visits (assessed up to 2 years) in metabolically abnormal obese individuals only.
Change in intra-hepatic triglyceride content
Intra-hepatic triglyceride content will be assessed by magnetic resonance techniques
Measured: Before and at annual follow-up visits (assessed up to 2 years) in metabolically abnormal obese individuals only.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2016Dec 2027

First posted11 Mar 2016 (estimated)
Study startFeb 2016
Primary completionApr 2025
Study completionDec 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (16)Papers the sponsor has linked to this study.
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: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 180 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02706262
Sponsor's protocol ID: PSQ-201512086
Status last verified: Jan 2026
First submitted: 24 Feb 2016
Last updated: 27 Jan 2026
Results posted: No
Data monitoring committee: Yes

Publications

Petersen MC, Smith GI, Palacios HH, Farabi SS, Yoshino M, Yoshino J, Cho K, Davila-Roman VG, Shankaran M, Barve RA, Yu J, Stern JH, Patterson BW, Hellerstein MK, Shulman GI, Patti GJ, Klein S. Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity. Cell Metab. 2024 Apr 2;36(4):745-761.e5. doi: 10.1016/j.cmet.2024.03.002.
PubMed 38569471
Mittendorfer B, van Vliet S, Smith GI, Petersen MC, Patterson BW, Klein S. Impaired plasma glucose clearance is a key determinant of fasting hyperglycemia in people with obesity. Obesity (Silver Spring). 2024 Mar;32(3):540-546. doi: 10.1002/oby.23963. Epub 2024 Jan 16.
PubMed 38228469
Seo JB, Riopel M, Cabrales P, Huh JY, Bandyopadhyay GK, Andreyev AY, Murphy AN, Beeman SC, Smith GI, Klein S, Lee YS, Olefsky JM. Knockdown of Ant2 Reduces Adipocyte Hypoxia And Improves Insulin Resistance in Obesity. Nat Metab. 2019 Jan;1(1):86-97. doi: 10.1038/s42255-018-0003-x. Epub 2018 Nov 19.
PubMed 31528845
Stern JH, Smith GI, Chen S, Unger RH, Klein S, Scherer PE. Obesity dysregulates fasting-induced changes in glucagon secretion. J Endocrinol. 2019 Nov;243(2):149-160. doi: 10.1530/JOE-19-0201.
PubMed 31454790
Eisenstein SA, Black KJ, Samara A, Koller JM, Dunn JP, Hershey T, Klein S, Smith GI. Striatal Dopamine Responses to Feeding are Altered in People with Obesity. Obesity (Silver Spring). 2020 Apr;28(4):765-771. doi: 10.1002/oby.22753. Epub 2020 Feb 21.
PubMed 32086877
Ding X, Iyer R, Novotny C, Metzger D, Zhou HH, Smith GI, Yoshino M, Yoshino J, Klein S, Swaminath G, Talukdar S, Zhou Y. Inhibition of Grb14, a negative modulator of insulin signaling, improves glucose homeostasis without causing cardiac dysfunction. Sci Rep. 2020 Feb 25;10(1):3417. doi: 10.1038/s41598-020-60290-1.
PubMed 32099031
Smith GI, Polidori DC, Yoshino M, Kearney ML, Patterson BW, Mittendorfer B, Klein S. Influence of adiposity, insulin resistance, and intrahepatic triglyceride content on insulin kinetics. J Clin Invest. 2020 Jun 1;130(6):3305-3314. doi: 10.1172/JCI136756.
PubMed 32191646
Smith GI, Shankaran M, Yoshino M, Schweitzer GG, Chondronikola M, Beals JW, Okunade AL, Patterson BW, Nyangau E, Field T, Sirlin CB, Talukdar S, Hellerstein MK, Klein S. Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease. J Clin Invest. 2020 Mar 2;130(3):1453-1460. doi: 10.1172/JCI134165.
PubMed 31805015
Cifarelli V, Beeman SC, Smith GI, Yoshino J, Morozov D, Beals JW, Kayser BD, Watrous JD, Jain M, Patterson BW, Klein S. Decreased adipose tissue oxygenation associates with insulin resistance in individuals with obesity. J Clin Invest. 2020 Dec 1;130(12):6688-6699. doi: 10.1172/JCI141828.
PubMed 33164985
Beals JW, Smith GI, Shankaran M, Fuchs A, Schweitzer GG, Yoshino J, Field T, Matthews M, Nyangau E, Morozov D, Mittendorfer B, Hellerstein MK, Klein S. Increased Adipose Tissue Fibrogenesis, Not Impaired Expandability, Is Associated With Nonalcoholic Fatty Liver Disease. Hepatology. 2021 Sep;74(3):1287-1299. doi: 10.1002/hep.31822. Epub 2021 Jun 22.
PubMed 33743554
Fuchs A, Samovski D, Smith GI, Cifarelli V, Farabi SS, Yoshino J, Pietka T, Chang SW, Ghosh S, Myckatyn TM, Klein S. Associations Among Adipose Tissue Immunology, Inflammation, Exosomes and Insulin Sensitivity in People With Obesity and Nonalcoholic Fatty Liver Disease. Gastroenterology. 2021 Sep;161(3):968-981.e12. doi: 10.1053/j.gastro.2021.05.008. Epub 2021 May 15.
PubMed 34004161
Farabi SS, Smith GI, Schweitzer GG, Stein RI, Klein S. Do lifestyle factors and quality of life differ in people with metabolically healthy and unhealthy obesity? Int J Obes (Lond). 2022 Oct;46(10):1778-1785. doi: 10.1038/s41366-022-01180-6. Epub 2022 Jul 11.
PubMed 35817849
Mittendorfer B, Patterson BW, Smith GI, Yoshino M, Klein S. beta Cell function and plasma insulin clearance in people with obesity and different glycemic status. J Clin Invest. 2022 Feb 1;132(3):e154068. doi: 10.1172/JCI154068.
PubMed 34905513
Dunn JP, Lamichhane B, Smith GI, Garner A, Wallendorf M, Hershey T, Klein S. Dorsal striatal response to taste is modified by obesity and insulin resistance. Obesity (Silver Spring). 2023 Aug;31(8):2065-2075. doi: 10.1002/oby.23799.
PubMed 37475685
Beals JW, Kayser BD, Smith GI, Schweitzer GG, Kirbach K, Kearney ML, Yoshino J, Rahman G, Knight R, Patterson BW, Klein S. Dietary weight loss-induced improvements in metabolic function are enhanced by exercise in people with obesity and prediabetes. Nat Metab. 2023 Jul;5(7):1221-1235. doi: 10.1038/s42255-023-00829-4. Epub 2023 Jun 26.
PubMed 37365374

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Study at a glance

From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Complex Effects of Dietary Manipulation on Metabolic Function, Inflammation and Health
ClinicalTrials.gov ID: NCT02706262
Acronym / sponsor ID: PSQ-201512086
Conditions: Obesity, Insulin Resistance
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 180 participants (estimated)
Lead sponsor: Washington University School of MedicineUniversity, hospital or other
Study start: Feb 2016
Primary completion: Apr 2025 (actual)
Study completion: Dec 2027 (estimated)
First posted: 11 Mar 2016 (estimated)
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.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Metabolically normal lean - Baseline testing only	No intervention	–Metabolically normal lean - Lean individuals that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content. Dietary intervention - None.
Metabolically normal obese - Baseline testing only	No intervention	–Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content. Dietary intervention - None.
Metabolically abnormal obese - Mediterranean diet	Experimental	Other: Metabolically abnormal obese - Mediterranean diet, Behavioral: Annual Follow-up VisitsMetabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver. Dietary intervention - A nutritionally balanced diet that includes fruits, vegetables, fish, beans, whole grains, and olive oil with approximately 50% of daily calories coming from complex carbohydrates, 30% of calories from fat, and 20% of calories from protein.
Metabolically abnormal obese - Low carbohydrate ketogenic diet	Experimental	Other: Metabolically abnormal obese - Low carbohydrate ketogenic diet, Behavioral: Annual Follow-up VisitsMetabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver. Dietary intervention - A very-low-carbohydrate, adequate protein, high-fat diet containing 20 grams of carbohydrate or less per day (about 5% of calories), derived mainly from vegetables.
Metabolically abnormal obese - Plant-based very-low-fat diet	Experimental	Other: Metabolically abnormal obese - Plant-based, very-low-fat diet, Behavioral: Annual Follow-up VisitsMetabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver. Dietary intervention - A plant-based diet high in complex carbohydrates and low in fat, protein, and sodium, with approximately 70% of daily calories from carbohydrates, 15% from fat, and 15% from protein.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

Metabolically normal lean subjects must have a BMI ≥18.5 and ≤24.9 kg/m2; Obese subjects must have a BMI ≥30.0 and ≤50.0 kg/m2
Metabolically normal lean and obese subjects must have intrahepatic triglyceride (IHTG) content ≤5%; plasma triglyceride (TG) concentration <150 mg/dl; fasting plasma glucose concentration <100 mg/dl, 2-hr oral glucose tolerance plasma glucose concentration <140 mg/dl, and hemoglobin A1C ≤5.6%
Metabolically abnormal obese subjects must have intrahepatic triglyceride (IHTG) content ≥5.6%; HbA1C ≥5.7%, 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 (19 listed)

Medical, surgical, or biological menopause
Previous bariatric surgery where the gastrointestinal tract is reconstructed such as Roux-en-Y, sleeve gastrectomy and biliopancreatic diversion surgeries
Laparoscopic adjustable gastric band (lab band) surgery within the last 3 years
Structured exercise ≥250 min per week (e.g., brisk walking)
Unstable weight (>4% change during the last 2 months before entering the study)

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
Metabolically abnormal obese - Mediterranean dietThe effect of consuming a Mediterranean diet will be examined over 3 different phases: (i) weight maintenance for 4 to 8 weeks, with all meals provided; (ii) controlled 7-10% weight loss with caloric intake reduced by 25% to achieve the desired amount of weight loss in about 4 to 5 months with all meals provided; and (iii) Independent weight loss for about 4 months. During the independent weight loss phase of the study subjects will be asked to continue to consume a Mediterranean diet but will prepare all their food at home. No food will be provided during this portion of the study.	Other	Metabolically abnormal obese - Mediterranean diet
Metabolically abnormal obese - Low carbohydrate ketogenic dietThe effect of consuming a low-carbohydrate, ketogenic diet will be examined over 3 different phases: (i) weight maintenance for 4 to 8 weeks, with all meals provided; (ii) controlled 7-10% weight loss with caloric intake reduced by 25% to achieve the desired amount of weight loss in about 4 to 5 months with all meals provided; and (iii) Independent weight loss for about 4 months. During the independent weight loss phase of the study subjects will be asked to continue to consume a low carbohydrate ketogenic diet but will prepare all their food at home. No food will be provided during this portion of the study.	Other	Metabolically abnormal obese - Low carbohydrate ketogenic diet
Metabolically abnormal obese - Plant-based, very-low-fat dietThe effect of consuming a plant-based, very-low-fat diet will be examined over 3 different phases: (i) weight maintenance for 4 to 8 weeks, with all meals provided; (ii) controlled 7-10% weight loss with caloric intake reduced by 25% to achieve the desired amount of weight loss in about 4 to 5 months with all meals provided; and (iii) Independent weight loss for about 4 months. During the independent weight loss phase of the study subjects will be asked to continue to consume a plant-based, very-low-fat diet but will prepare all their food at home. No food will be provided during this portion of the study.	Other	Metabolically abnormal obese - Plant-based very-low-fat diet
Annual Follow-up VisitsMetabolic health will be assessed 1 and 2-years after competing the diet intervention study. No intervention will be performed during the time.	Behavioural	Metabolically abnormal obese - Low carbohydrate ketogenic diet, Metabolically abnormal obese - Mediterranean diet, Metabolically abnormal obese - Plant-based very-low-fat diet

Primary outcome

Insulin sensitivity
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Change in insulin sensitivity
Time frame: Before and after 4 to 8-weeks of weight maintenance and after 7-10% weight loss (~6-7 months)
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure

59 secondary outcomes

24-hour glucose concentrations
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in 24-hour glucose concentrations
Time frame: Before and after 4 to 8-weeks of weight maintenance and after 7-10% weight loss (~6-7 months)
24-hour hormone concentrations
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in 24-hour hormone concentrations
Time frame: Before and after 4 to 8-weeks of weight maintenance and after 7-10% weight loss (~6-7 months)
24-hour cytokine concentrations
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
β-cell function
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in β-cell function
Time frame: Before and after 7-10% weight loss (~6-7 months) and independent weight loss (12 months) in metabolically abnormal obese individuals only.
Insulin clearance
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Insulin clearance
Time frame: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only.
Fat mass and fat free mass
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in fat mass and fat free mass
Time frame: Before and after 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
Exosome-mediated intercellular signaling
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in exosome-mediated intercellular signaling
Time frame: Before and after 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
Abdominal adipose tissue volumes
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in abdominal adipose tissue volumes
Time frame: Before and after 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
Leg adipose tissue volumes
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in leg adipose tissue volumes
Time frame: Before and after 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
Intra-hepatic triglyceride content
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in intra-hepatic triglyceride content
Time frame: Before and after 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
Gut microbiome
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in gut microbiome
Time frame: Before and during 4 to 8-weeks of weight maintenance, 7-10% weight loss (~6-7 months) and independent weight loss (12 months)
Plasma lipid profile
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in plasma lipid profile
Time frame: Before and after 4 to 8-weeks of weight maintenance, after 7-10% weight loss (~6-7 months) and after independent weight loss (12 months)
Aerobic fitness
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in aerobic fitness
Time frame: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals randomized to the plant-based very-low-fat diet only
Carotid artery intima media thickness
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in carotid artery intima media thickness
Time frame: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Cardiac structure and function
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in cardiac structure and function
Time frame: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Endothelial function
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in endothelial function
Time frame: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Arterial stiffness
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in arterial stiffness
Time frame: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Physical activity
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in physical activity
Time frame: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Sleep efficiency
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in sleep efficiency
Time frame: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Rate of incorporation of 2H2O into lipids
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).
Change in the rate of incorporation of 2H2O into lipids
Time frame: Before and after 7-10% weight loss (~6-7 months) in metabolically abnormal obese individuals only
Rate of incorporation of 2H2O into proteins
Time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).

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 27 Jan 2026.
Background: PubMed 38569471Petersen MC, Smith GI, Palacios HH, Farabi SS, Yoshino M, Yoshino J, Cho K, Davila-Roman VG, Shankaran M, Barve RA, Yu J, Stern JH, Patterson BW, Hellerstein MK, Shulman GI, Patti GJ, Klein S. Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity. Cell Metab. 2024 Apr 2;36(4):745-761.e5. doi: 10.1016/j.cmet.2024.03.002.
Background: PubMed 38228469Mittendorfer B, van Vliet S, Smith GI, Petersen MC, Patterson BW, Klein S. Impaired plasma glucose clearance is a key determinant of fasting hyperglycemia in people with obesity. Obesity (Silver Spring). 2024 Mar;32(3):540-546. doi: 10.1002/oby.23963. Epub 2024 Jan 16.
Results publication: PubMed 31528845Seo JB, Riopel M, Cabrales P, Huh JY, Bandyopadhyay GK, Andreyev AY, Murphy AN, Beeman SC, Smith GI, Klein S, Lee YS, Olefsky JM. Knockdown of Ant2 Reduces Adipocyte Hypoxia And Improves Insulin Resistance in Obesity. Nat Metab. 2019 Jan;1(1):86-97. doi: 10.1038/s42255-018-0003-x. Epub 2018 Nov 19.
Results publication: PubMed 31454790Stern JH, Smith GI, Chen S, Unger RH, Klein S, Scherer PE. Obesity dysregulates fasting-induced changes in glucagon secretion. J Endocrinol. 2019 Nov;243(2):149-160. doi: 10.1530/JOE-19-0201.
Results publication: PubMed 32086877Eisenstein SA, Black KJ, Samara A, Koller JM, Dunn JP, Hershey T, Klein S, Smith GI. Striatal Dopamine Responses to Feeding are Altered in People with Obesity. Obesity (Silver Spring). 2020 Apr;28(4):765-771. doi: 10.1002/oby.22753. Epub 2020 Feb 21.
Results publication: PubMed 32099031Ding X, Iyer R, Novotny C, Metzger D, Zhou HH, Smith GI, Yoshino M, Yoshino J, Klein S, Swaminath G, Talukdar S, Zhou Y. Inhibition of Grb14, a negative modulator of insulin signaling, improves glucose homeostasis without causing cardiac dysfunction. Sci Rep. 2020 Feb 25;10(1):3417. doi: 10.1038/s41598-020-60290-1.
Results publication: PubMed 32191646Smith GI, Polidori DC, Yoshino M, Kearney ML, Patterson BW, Mittendorfer B, Klein S. Influence of adiposity, insulin resistance, and intrahepatic triglyceride content on insulin kinetics. J Clin Invest. 2020 Jun 1;130(6):3305-3314. doi: 10.1172/JCI136756.
Results publication: PubMed 31805015Smith GI, Shankaran M, Yoshino M, Schweitzer GG, Chondronikola M, Beals JW, Okunade AL, Patterson BW, Nyangau E, Field T, Sirlin CB, Talukdar S, Hellerstein MK, Klein S. Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease. J Clin Invest. 2020 Mar 2;130(3):1453-1460. doi: 10.1172/JCI134165.
Results publication: PubMed 33164985Cifarelli V, Beeman SC, Smith GI, Yoshino J, Morozov D, Beals JW, Kayser BD, Watrous JD, Jain M, Patterson BW, Klein S. Decreased adipose tissue oxygenation associates with insulin resistance in individuals with obesity. J Clin Invest. 2020 Dec 1;130(12):6688-6699. doi: 10.1172/JCI141828.
Results publication: PubMed 33743554Beals JW, Smith GI, Shankaran M, Fuchs A, Schweitzer GG, Yoshino J, Field T, Matthews M, Nyangau E, Morozov D, Mittendorfer B, Hellerstein MK, Klein S. Increased Adipose Tissue Fibrogenesis, Not Impaired Expandability, Is Associated With Nonalcoholic Fatty Liver Disease. Hepatology. 2021 Sep;74(3):1287-1299. doi: 10.1002/hep.31822. Epub 2021 Jun 22.
Results publication: PubMed 34004161Fuchs A, Samovski D, Smith GI, Cifarelli V, Farabi SS, Yoshino J, Pietka T, Chang SW, Ghosh S, Myckatyn TM, Klein S. Associations Among Adipose Tissue Immunology, Inflammation, Exosomes and Insulin Sensitivity in People With Obesity and Nonalcoholic Fatty Liver Disease. Gastroenterology. 2021 Sep;161(3):968-981.e12. doi: 10.1053/j.gastro.2021.05.008. Epub 2021 May 15.
Results publication: PubMed 35817849Farabi SS, Smith GI, Schweitzer GG, Stein RI, Klein S. Do lifestyle factors and quality of life differ in people with metabolically healthy and unhealthy obesity? Int J Obes (Lond). 2022 Oct;46(10):1778-1785. doi: 10.1038/s41366-022-01180-6. Epub 2022 Jul 11.

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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. This study is not recruiting at the moment.

Samuel Klein, MD 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?

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 19 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: under way, not looking for participants, as of the sponsor's last update on 27 Jan 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Insulin sensitivity (time frame: Baseline only (cross-sectional comparison of metabolically normal lean, metabolically normal obese and metabolically abnormal obese subjects).). 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?

On the ClinicalTrials.gov record for NCT02706262, which also lists 16 linked publications.

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 27 Jan 2026; AzTrials last refreshed its copy on 1 Nov 2026.