Clinical trial NCT01104220: Role of Immune System in Obesity-related Inflammation and Cardiometabolic Risk
Official title: Role of Immune System in Obesity-related Inflammation and Cardiometabolic Risk
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease
Metabolic Syndrome
Metabolically Abnormal Obesity
Metabolically Normal Obesity
Obesity
Keywords: NAFLD
Obesity
Metabolic syndrome
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2010-04-15
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Insulin sensitivity
timeFrame: Baseline
Secondary outcomes:
measure: TNF-alpha
timeFrame: Baseline
measure: Interleukin-6 (IL-6)
timeFrame: Baseline
measure: Liver tissue inflammation
timeFrame: Baseline
measure: Abdominal adipose tissue inflammation
timeFrame: Baseline only in participants scheduled for bariatric surgery
measure: Abdominal adipose tissue inflammation
timeFrame: Baseline only in participants scheduled for gallbladder, inguinal hernia, hysterectomy or myomectomy surgery
measure: Upper vs lower adipose tissue inflammation
timeFrame: Baseline (All groups)
measure: Exosome-mediated intercellular signaling
timeFrame: Baseline only in participants scheduled for bariatric surgery
measure: Exosome-mediated intercellular signaling
timeFrame: Baseline only in participants scheduled for gallbladder, inguinal hernia, hysterectomy or myomectomy surgery
measure: Exosome-mediated intercellular signaling
timeFrame: Baseline only in all participants
measure: Change in exosome-mediated intercellular signaling
timeFrame: Before and after 20-30% weight loss (~3-4 months) in participants scheduled for bariatric surgery
measure: Hepatic PNPLA3 synthesis rate
timeFrame: Baseline only in people scheduled for gallbladder or bariatric surgery
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Samuel Klein, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.