Precision Nutrition and Metabolic Function

Obesity Clinical Trial

Official title:

Precision Nutrition and Metabolic Function

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04131166
• Other study ID #: 201908237
• Status: Recruiting
• Phase: N/A
• Start date: October 8, 2019
• Est. completion date: December 31, 2029

Study information

• Verified date: May 2024
• Source: Washington University School of Medicine
• Contact: Brittney Mason
• Phone: 314-273-1879
• Email: nutritionresearch[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purposes of this study are: 1) to determine the mechanisms responsible for the development of cardiometabolic complications in some, but not all people with obesity; 2) determine the best dietary approach for cardiometabolic health; and 3) understand why some people have a stable metabolic phenotype over time whereas cardiometabolic health improves or worsens in others.

Description:

Excess adiposity causes alterations in metabolic function including impaired glucose homeostasis and insulin resistance, which are important risk factors for type 2 diabetes (T2D) and cardiovascular disease (CVD). Not all people with obesity experience the typical metabolic complications associated with obesity. Approximately 25% of people with obesity are protected from the adverse metabolic effects of excess fat accumulation and are considered to be metabolically healthy based on their normal response to insulin. The mechanism(s) responsible for the differences in metabolic function among people with obesity is not known, but is likely to be multifactorial including dietary intake. The risk for developing T2D and CVD is also well known to increase with age, however, not all people that are metabolically healthy convert to a metabolically unhealthy phenotype over time. The mechanisms responsible for the stability of health status in some, but not all adults, are unclear. The overall goals of this study are to: i) determine the mechanisms responsible for the development of cardiometabolic complications in participants who will be carefully characterized into 3 distinct groups [metabolically normal lean, metabolically normal obese and metabolically abnormal obese], ii) to determine the optimal dietary approach for cardiometabolic health independent of weight change in people with metabolically abnormal obesity, and iii) perform a comprehensive longitudinal assessment of cardiometabolic health to understand why some people have a stable metabolic phenotype over time whereas cardiometabolic health improves or worsens in others.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2029
• Est. primary completion date: October 1, 2029
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Metabolically healthy lean subjects must have a body mass index (BMI) 18.5-24.9 kg/m2, intrahepatic triglyceride (IHTG) content =5%, serum triglyceride (TG) concentration <150 mg/dl, fasting plasma glucose concentration <100 mg/dl, 2-hr oral glucose tolerance test (OGTT) plasma glucose concentration =140 mg/dl, and hemoglobin A1C (HbA1C) =5.6%.

• Metabolically healthy obese subjects must have a BMI 30-49.9 kg/m2; IHTG content =5%, serum TG concentration <150 mg/dl, fasting plasma glucose concentration <100 mg/dl, 2-hr OGTT plasma glucose concentration =140 mg/dl, and HbA1C =5.6%.

• Metabolically unhealthy obese subjects must have a BMI 30-49.9 kg/m2; IHTG content =5.6% and fasting plasma glucose concentration =100 mg/dl or 2-hr OGTT plasma glucose concentration =140 mg/dl or HbA1C =5.7%.

Exclusion Criteria:

• 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);

• cancer or cancer that has been in remission for <5 years;

• polycystic ovary syndrome;

• 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);

• severe anemia;

• regular use of tobacco products;

• excessive consumption of alcohol (=3 drinks/day for men and =2 drinks/day for women);

• 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;

• 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

Related Conditions & MeSH terms

• Insulin Resistance
• Obesity

Intervention

Behavioral:
• Mediterranean diet
A Mediterranean-type diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.
• Low-carbohydrate, ketogenic diet
A low-carbohydrate, ketogenic diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.
• Low-fat diet
A low-fat diet will be consumed for 4 to 8 weeks in the weight stable state with all meals provided.

Other:
• Annual follow-up testing for 5 years
Annual follow-up testing with no restrictions on dietary intake during periods between annual testing.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Centene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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, metabolically healthy obese and metabolically unhealthy obese subjects).
Primary	Change in insulin sensitivity	Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure	Before and after 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet
Primary	Change in insulin sensitivity	Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure	Performed annually for 5 years
Secondary	24-hour glucose concentrations	Plasma glucose concentrations will be evaluated from frequent blood samples over a 24 h period	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	Change in 24-hour glucose concentrations	Plasma glucose concentrations will be evaluated from frequent blood sampling over a 24 h period	Before and after 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet
Secondary	Change in 24-hour glucose concentrations	Plasma glucose concentrations will be evaluated from frequent blood sampling over a 24 h period	Performed annually for 5 years
Secondary	24-hour hormone concentrations	Plasma hormone concentrations will be evaluated from frequent blood sampling over a 24 h period	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	Change in 24-hour hormone concentrations	Plasma hormone concentrations will be evaluated from frequent blood samples over a 24 h period	Before and after 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet
Secondary	Change in 24-hour hormone concentrations	Plasma hormone concentrations will be evaluated from frequent blood samples over a 24 h period	Performed annually for 5 years
Secondary	ß-cell function	ß-cell function will be assessed from a modified oral glucose tolerance test	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	Change in ß-cell function	ß-cell function will be assessed from a modified oral glucose tolerance test	Performed annually for 5 years
Secondary	Insulin clearance	Insulin clearance will be assessed from a modified oral glucose tolerance test and hyperinsulinemic-euglycemic clamp procedure	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	Change in Insulin clearance	Insulin clearance will be assessed from a modified oral glucose tolerance test and hyperinsulinemic-euglycemic clamp procedure	Performed annually for 5 years
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, metabolically healthy obese and metabolically unhealthy obese subjects).
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 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet
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)	Performed annually for 5 years
Secondary	Exosome-mediated intercellular signaling	Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	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	Before and after 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet
Secondary	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	Performed annually for 5 years
Secondary	Intrahepatic triglyceride content	Intrahepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	Change in intra-hepatic triglyceride content	Intra-hepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)	Before and after 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet
Secondary	Change in intra-hepatic triglyceride content	Intra-hepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)	Performed annually for 5 years
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, metabolically healthy obese and metabolically unhealthy obese subjects).
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 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet
Secondary	Change in abdominal adipose tissue volumes	Abdominal subcutaneous and intra-abdominal adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)	Performed annually for 5 years
Secondary	Leg adipose tissue volumes	Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	Change in leg adipose tissue volumes	Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)	Before and after 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet
Secondary	Change in leg adipose tissue volumes	Thigh and calf adipose tissue volumes will be assessed by magnetic resonance imagining (MRI)	Performed annually for 5 years
Secondary	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	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	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	Before and after 4-8 weeks of weight maintenance in metabolically healthy and unhealthy obese subjects randomized to follow a Mediterranean, low-carbohydrate or low-fat diet
Secondary	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	Performed annually for 5 years
Secondary	Carotid artery intima media thickness	Carotid artery intima media thickness will be assessed by ultrasound imaging	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	Change in carotid artery intima media thickness	Carotid artery intima media thickness will be assessed by ultrasound imaging	Performed annually for 5 years
Secondary	Cardiac structure and function	Ultrasound techniques will be used to assess cardiac structure and function	Baseline only (cross-sectional comparison of metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	Change in cardiac structure and function	Ultrasound techniques will be used to assess cardiac structure and function	Performed annually for 5 years in metabolically healthy obese and metabolically unhealthy obese subjects.
Secondary	Endothelial function	Endothelial function will be assessed using a non-invasive device (EndoPat 2000) in response to reactive hyperemia.	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	Change in endothelial function	Endothelial function will be assessed using a non-invasive device (EndoPat 2000) in response to reactive hyperemia.	Performed annually for 5 years
Secondary	Arterial stiffness	Arterial stiffness will be assessed using a non-invasive device (SphygmoCor)	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	Change in arterial stiffness	Arterial stiffness will be assessed using a non-invasive device (SphygmoCor)	Performed annually for 5 years
Secondary	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	Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Secondary	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	Performed annually for 5 years