Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance

Obesity Clinical Trial

Official title:

Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05165706
• Other study ID #: 40195
• Secondary ID: 5R01DK110186-02
• Status: Recruiting
• Phase: N/A
• Start date: January 31, 2019
• Est. completion date: December 30, 2024

Study information

• Verified date: April 2023
• Source: Stanford University
• Contact: Ekrem M Ayhan, BS
• Phone: 908-619-5381
• Email: ayhane[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This 12-week controlled diet and weight intervention study seeks to define the molecular pathways that link excess body weight to the development of insulin resistance (IR). Blood, adipose and stool are sampled at three timepoints; baseline, peak weight (4 weeks) and post weight loss to monitor changes in cellular processes. Additionally, direct insulin sensitivity testing, and radiological measurement of visceral fat and intrahepatic fat content is measured at three timepoints to correlate clinical indices with cellular changes.

Description:

Obesity has become an epidemic worldwide. Metabolic/cardiovascular complications of obesity are likely related to the fact that obese individuals tend to be insulin resistant (IR). While insulin- mediated glucose uptake (IMGU) correlates with adipose tissue mass, not all obese individuals are IR, and metabolic and cardiovascular profiles of those who are IR vs insulin sensitive (IS) differ significantly. Why one individual who reaches a BMI of 30 kg/m2 will develop IR and another with similar BMI and activity level remains IS is unclear. Furthermore, while insulin sensitivity improves with weight loss, this response varies as well. Given that fat mass per se does not fully explain the obesity contribution to IMGU, itis likely that differential adipocyte function plays a role. With this study, our purpose is to employ an integrated omics strategy to identify analyte/pathway signatures in blood and adipose tissue that characterize IR versus IS states and expand our biological knowledge of the mechanisms underlying IR.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: December 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 35 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age 35-65

• BMI 25-35 kg/m2

• Stable body weight

• Nondiabetic

Exclusion Criteria:

Patients with;

• diabetes

• major organ disease

• history of liposuction or bariatric surgery

• active eating or psychiatric disorder

• pregnancy or lactation, heavy alcohol use

• recent change in weight (over the past 12 weeks)

• use of weight loss medication, statins, or oral steroids

Clinical screening exclusions;

• hematocrit < 33%

• fasting glucose >/= 126 mg/dL

• blood pressure >160/100 mmHg

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Diet Modification
• Fatty Liver
• Insulin Resistance
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver
• Nonalcoholic Steatohepatitis
• Obesity
• PreDiabetes

Intervention

Behavioral:
• Dietary Intervention Mediterranean Low Carbohydrate Diet
Assigned participants will receive instruction by a registered dietitian on a diet that is high in unsaturated fats and low in carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.
• Dietary Intervention Standard Low Carbohydrate Diet
Assigned participants will receive instruction by a registered dietitian on a low carbohydrate diet that is high in fats found in the typical American diet. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.
• Dietary Intervention Standard Low Fat Diet
Assigned participants will receive instruction by a registered dietitian on a low fat diet that is high in complex carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline on the 2-stage Steady State Plasma Glucose test	Compare direct measurement of insulin sensitivity after 4 week diet and weight intervention	Peak weight (4 weeks)
Primary	Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio	Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 4 week diet and weight intervention	Peak weight (4 weeks)
Primary	Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition	Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 4 week diet and weight intervention	Peak weight (4 weeks)
Primary	Change from peak weight on the 2-stage Steady State Plasma Glucose test	Compare direct measurement of insulin sensitivity after 8 week diet and weight intervention	Post-weight loss (8 weeks)
Primary	Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio	Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 8 week diet and weight intervention	Post-weight loss (8 weeks)
Primary	Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition	Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 8 week diet and weight intervention	Post-weight loss (8 weeks)
Primary	Measurement of markers of lipid and carbohydrate metabolism and inflammation from adipose mRNA	Compare adipose tissue transcripts such as known MODY transcription factors, defensin chemokine receptors, and platelet activation factors measured by PCR between participants identified as Insulin sensitive (IS) and Insulin resistant (IR) using the 2-stage Steady State Plasma Glucose test.	Baseline
Primary	Quantification of plasma inflammatory cytokine levels in serum samples by Luminex immunoassay	Compare plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay between participants identified as Insulin Sensitive (IS) and Insulin Resistant (IR) using the 2-stage Steady State Plasma Glucose test.	Baseline
Primary	Change from baseline in plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay	Compare intra-personal levels of plasma inflammatory cytokines as measured by Luminex immunoassay after 4 week diet and weight intervention	Peak Weight (4 weeks)