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

Primary Purpose

Non-alcoholic Fatty Liver Disease, Metabolic Syndrome, Metabolically Abnormal Obesity

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Weight loss

About this trial

This is an interventional other trial for Non-alcoholic Fatty Liver Disease focused on measuring NAFLD, Obesity, Metabolic syndrome

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Washington University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

No Intervention

Experimental

No Intervention

Arm Label

Lean, metabolically normal

Obese, metabolically normal

Obese, metabolically abnormal

Obese, scheduled for bariatric surgery

Obese, scheduled for gallbladder surgery

Lean, scheduled for inguinal hernia, hysterectomy or myomectomy surgery

Arm Description

Subjects with body mass index 18.5 - 24.9 kg/m² and normal fasting blood glucose and oral glucose tolerance and liver fat.

Subjects with body mass index ≥30.0 kg/m² and normal fasting blood glucose and oral glucose tolerance and liver fat.

Subjects with body mass index ≥30.0 kg/m² and impaired fasting or oral glucose tolerance and increased liver fat.

Subjects with a body mass index ≥35.0 kg/m² undergoing bariatric surgery

Subjects with a body mass index ≥35.0 kg/m² undergoing gallbladder surgery

Subjects with body mass index 18.5 - 24.9 kg/m² and normal fasting blood glucose and oral glucose tolerance and liver fat.

Outcomes

Primary Outcome Measures

Insulin sensitivity

Insulin sensitivity assessed in vivo by using a hyperinsulinemic-euglycemic clamp procedure with stable isotope tracer infusion

Secondary Outcome Measures

TNF-alpha

TNF-alpha is a marker of inflammation

Interleukin-6 (IL-6)

Interleukin-6 is a marker of inflammation

Liver tissue inflammation

Liver immune cell content

Abdominal adipose tissue inflammation

Subcutaneous, omental and transverse mesocolic adipose tissue

Abdominal adipose tissue inflammation

Subcutaneous and omental adipose tissue

Upper vs lower adipose tissue inflammation

Immune cell content in abdominal and femoral subcutaneous adipose tissue

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.

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

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.

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

Hepatic PNPLA3 synthesis rate

Synthesis rates assessed by stable isotope techniques in the fasted vs the fed states

Full Information

NCT ID

NCT01104220

First Posted

April 13, 2010

Last Updated

August 4, 2023

Sponsor

Washington University School of Medicine

Collaborators

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT01104220

Brief Title

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

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 2010 (Actual)

Primary Completion Date

September 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

Collaborators

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-alcoholic Fatty Liver Disease, Metabolic Syndrome, Metabolically Abnormal Obesity, Metabolically Normal Obesity, Obesity

Keywords

NAFLD, Obesity, Metabolic syndrome

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

144 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Lean, metabolically normal

Arm Type

No Intervention

Arm Description

Subjects with body mass index 18.5 - 24.9 kg/m² and normal fasting blood glucose and oral glucose tolerance and liver fat.

Arm Title

Obese, metabolically normal

Arm Type

No Intervention

Arm Description

Subjects with body mass index ≥30.0 kg/m² and normal fasting blood glucose and oral glucose tolerance and liver fat.

Arm Title

Obese, metabolically abnormal

Arm Type

No Intervention

Arm Description

Subjects with body mass index ≥30.0 kg/m² and impaired fasting or oral glucose tolerance and increased liver fat.

Arm Title

Obese, scheduled for bariatric surgery

Arm Type

Experimental

Arm Description

Subjects with a body mass index ≥35.0 kg/m² undergoing bariatric surgery

Arm Title

Obese, scheduled for gallbladder surgery

Arm Type

No Intervention

Arm Description

Subjects with a body mass index ≥35.0 kg/m² undergoing gallbladder surgery

Arm Title

Lean, scheduled for inguinal hernia, hysterectomy or myomectomy surgery

Arm Type

No Intervention

Arm Description

Subjects with body mass index 18.5 - 24.9 kg/m² and normal fasting blood glucose and oral glucose tolerance and liver fat.

Intervention Type

Other

Intervention Name(s)

Weight loss

Intervention Description

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

Primary Outcome Measure Information:

Title

Insulin sensitivity

Description

Insulin sensitivity assessed in vivo by using a hyperinsulinemic-euglycemic clamp procedure with stable isotope tracer infusion

Time Frame

Baseline

Secondary Outcome Measure Information:

Title

TNF-alpha

Description

TNF-alpha is a marker of inflammation

Time Frame

Baseline

Title

Interleukin-6 (IL-6)

Description

Interleukin-6 is a marker of inflammation

Time Frame

Baseline

Title

Liver tissue inflammation

Description

Liver immune cell content

Time Frame

Baseline

Title

Abdominal adipose tissue inflammation

Description

Subcutaneous, omental and transverse mesocolic adipose tissue

Time Frame

Baseline only in participants scheduled for bariatric surgery

Title

Abdominal adipose tissue inflammation

Description

Subcutaneous and omental adipose tissue

Time Frame

Baseline only in participants scheduled for gallbladder, inguinal hernia, hysterectomy or myomectomy surgery

Title

Upper vs lower adipose tissue inflammation

Description

Immune cell content in abdominal and femoral subcutaneous adipose tissue

Time Frame

Baseline (All groups)

Title

Exosome-mediated intercellular signaling

Description

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.

Time Frame

Baseline only in participants scheduled for bariatric surgery

Title

Exosome-mediated intercellular signaling

Description

Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood, subcutaneous and omental adipose tissue

Time Frame

Baseline only in participants scheduled for gallbladder, inguinal hernia, hysterectomy or myomectomy surgery

Title

Exosome-mediated intercellular signaling

Description

Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and abdominal and femoral subcutaneous adipose tissue.

Time Frame

Baseline only in all participants

Title

Change in exosome-mediated intercellular signaling

Description

Signaling between cells and organs will be examined by isolating exosomes (small extracellular vesicles) from blood and adipose tissue

Time Frame

Before and after 20-30% weight loss (~3-4 months) in participants scheduled for bariatric surgery

Title

Hepatic PNPLA3 synthesis rate

Description

Synthesis rates assessed by stable isotope techniques in the fasted vs the fed states

Time Frame

Baseline only in people scheduled for gallbladder or bariatric surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Beth Henk

Phone

314-362-8250

bhenk@wustl.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Samuel Klein, M.D.

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Citations:

PubMed Identifier

31004409

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.

Results Reference

result

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

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