Role of Immune System in Obesity-related Inflammation and Cardiometabolic Risk

Obesity Clinical Trial

Official title:

Role of Immune System in Obesity-related Inflammation and Cardiometabolic Risk

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01104220
• Other study ID #: 201102127
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 2010
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to learn more about how the body stores fat in and around organs (for example in the liver) and why this affects some people's health more than others. Understanding this may lead to better treatments for diseases such as diabetes and cardiovascular disease.

Description:

The purpose of this study is to determine the specific cellular and organ system metabolic and immunologic alterations that are associated with insulin resistance and inflammation in order to identify putative mechanisms and novel bio-markers involved in the pathogenesis and progression of inflammatory and cardiometabolic diseases.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 144
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

Lean, metabolically healthy group - Body mass index (BMI) 18.5-24.9 kg/m2, HbA1C =5.6%, fasting plasma glucose concentration <100 mg/dl, 2-h OGTT plasma glucose concentration <140 mg/dl and intrahepatic triglyceride (IHTG) content =5%.

Obese, metabolically healthy group - BMI =30 kg/m2, HHbA1C =5.6%, fasting plasma glucose concentration <100 mg/dl, 2-h OGTT plasma glucose concentration <140 mg/dl and intrahepatic triglyceride (IHTG) content =5%.

Obese, metabolically healthy group - BMI =30 kg/m2, IHTG content =5.6% and HbA1C =5.7% or fasting plasma glucose concentration =100 mg/dl or 2-h OGTT plasma glucose concentration =140 mg/dl.

Lean, scheduled for inguinal hernia, hysterectomy or myomectomy surgery - BMI 18.5-24.9 kg/m2, HbA1C =5.6%, fasting plasma glucose concentration <100 mg/dl, 2-h OGTT plasma glucose concentration <140 mg/dl and IHTG content =5%.

Obese, scheduled for bariatric and gallbladder surgery - BMI =35.0kg/m2

Exclusion Criteria:

• active or previous history of liver diseases other than NAFLD

• history of alcohol abuse

• currently consuming =20 g alcohol/day

• severe hypertriglyceridemia (>300 mg/dL)

• smoke tobacco

• cancer diagnosis within the previous 5 years

• medications that might confound the study results

• pregnancy or lactation

• exercise >2 h/week

Related Conditions & MeSH terms

• Fatty Liver
• Inflammation
• Liver Diseases
• Metabolic Syndrome
• Metabolically Abnormal Obesity
• Metabolically Normal Obesity
• Non-alcoholic Fatty Liver Disease
• Obesity

Intervention

Other:
• Weight loss
Bariatric surgery-induced weight loss to achieve ~20%-30% reduction in initial body weight

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	Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (1)

Yoshino J, Patterson BW, Klein S. Adipose Tissue CTGF Expression is Associated with Adiposity and Insulin Resistance in Humans. Obesity (Silver Spring). 2019 Jun;27(6):957-962. doi: 10.1002/oby.22463. Epub 2019 Apr 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin sensitivity	Insulin sensitivity assessed in vivo by using a hyperinsulinemic-euglycemic clamp procedure with stable isotope tracer infusion	Baseline
Secondary	TNF-alpha	TNF-alpha is a marker of inflammation	Baseline
Secondary	Interleukin-6 (IL-6)	Interleukin-6 is a marker of inflammation	Baseline
Secondary	Liver tissue inflammation	Liver immune cell content	Baseline
Secondary	Abdominal adipose tissue inflammation	Subcutaneous, omental and transverse mesocolic adipose tissue	Baseline only in participants scheduled for bariatric surgery
Secondary	Abdominal adipose tissue inflammation	Subcutaneous and omental adipose tissue	Baseline only in participants scheduled for gallbladder, inguinal hernia, hysterectomy or myomectomy surgery
Secondary	Upper vs lower adipose tissue inflammation	Immune cell content in abdominal and femoral subcutaneous adipose tissue	Baseline (All groups)
Secondary	Exosome-mediated intercellular signaling	Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood, subcutaneous, omental and transverse mesocolic adipose tissue and liver.	Baseline only in participants scheduled for bariatric surgery
Secondary	Exosome-mediated intercellular signaling	Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood, subcutaneous and omental adipose tissue	Baseline only in participants scheduled for gallbladder, inguinal hernia, hysterectomy or myomectomy surgery
Secondary	Exosome-mediated intercellular signaling	Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and abdominal and femoral subcutaneous adipose tissue.	Baseline only in all participants
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 20-30% weight loss (~3-4 months) in participants scheduled for bariatric surgery
Secondary	Hepatic PNPLA3 synthesis rate	Synthesis rates assessed by stable isotope techniques in the fasted vs the fed states	Baseline only in people scheduled for gallbladder or bariatric surgery