Stanford, California 94305

  • Inflammation

Purpose:

The proposed study is designed to test the hypothesis that in human obesity, the balance of pro- and anti-inflammatory T cells in fat tissue is in fact related to macrophage phenotype and insulin resistance, and how it is related. This study is needed to confirm whether conclusions based on studies of visceral adipose tissue in mice are indeed applicable to humans. We also want to determine the relationship between insulin resistance/hyperinsulinemia and ability to lose weight in obese individuals.


Study summary:

Previous studies have found convincing evidence of the relationship between insulin resistance, T cell profiles, macrophage profiles and inflammation of the fat cells. This study will add human subjects to that body of evidence. Overview Aim 1: Test the hypothesis that the balance of anti- inflammatory vs proinflammatory T cells is protective for systemic insulin resistance. T cell profiles in subcutaneous and visceral tissue and blood will be compared in IR vs IS obese humans at baseline and potentially after 12 months following weight loss. Tcell profile will be evaluated for relationships with IR and inflammation, with adjustment for total body fat. Secondarily, they will be evaluated for relationship to adipose cell size. Overview Aim 2: Test the hypothesis that macrophage phenotype in adipose tissue is associated with T cell profile and IR. Frequency of macrophage phenotypes (M1 vs M2) will be analyzed in IR vs IS obese humans at baseline and potentially after 12 months following weight loss. Overview Aim 3: Testing the hypothesis insulin resistance is associated with T cell receptor phenotypes in subcutaneous and visceral tissue. IR and IS subjects will be evaluated at baseline by sequencing of expressed TCRs in paired SAT, VAT, and blood. We will determine whether TCR phenotypes are shared between different IR individuals.


Criteria:

Inclusion Criteria: - Current patients of Stanford Healthcare, Bariatric Surgery Clinic, scheduled to undergo bariatric surgery (sleeve or RYGB) - BMI 30-55kg/m2 - 30-65 years of age - good general health, no major organ disease - non-diabetic by current American Diabetes Association (ADA) criteria (fasting glucose <126mg/dl) Exclusion Criteria: - Subjects with any clinical or biochemical evidence of significant anemia, gastrointestinal, cardiac, hepatic or renal disease will be excluded. - Subjects with other medical problems may participate as long as the problems are stable. - Subjects with active psychiatric disorders or past history of bariatric surgery - Pregnant or lactating women will also be excluded from the study, due to possible risk to the fetus or infant.


Study is Available At:


Original ID:

40196


NCT ID:

NCT04708535


Secondary ID:

1-19-ICTS-073


Study Acronym:


Brief Title:

Adaptive Immune Response in Visceral and Subcutaneous Fat: Role in Human Insulin Resistance


Official Title:

Adaptive Immune Response in Visceral and Subcutaneous Fat: Role in Human Insulin Resistance


Overall Status:

Enrolling by invitation


Study Phase:

N/A


Genders:

N/A


Minimum Age:

30 Years


Maximum Age:

65 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Stanford University


Oversight Authority:

There was an error processing this request


Reasons Why Stopped:


Study Type:

Observational


Study Design:


Number of Arms:

0


Number of Groups:

1


Total Enrollment:

50


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Tracey McLaughlin, MD
Principal Investigator
Stanford University

Study Dates

Start Date:August 1, 2017
Completion Date:June 30, 2021
Completion Type:Anticipated
Primary Completion Date:June 30, 2021
Primary Completion Type:Anticipated
Verification Date:January 2021
Last Changed Date:January 11, 2021
First Received Date:July 3, 2018

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Change in body weight
Time Frame:post-operatively (1-2 years status post bariatric surgery)
Safety Issues:False
Description:Percent body weight loss post bariatric surgery, accounting for insulin sensitivity, T-cell profile, cell size, and macrophage and T-cell phenotypes.
Outcome Type:Secondary Outcome
Measure:Change in body weight
Time Frame:(Timeframe: baseline (within 2 months prior to bariatric surgery)
Safety Issues:False
Description:Percent body weight loss post bariatric surgery, accounting for insulin sensitivity, T-cell profile, cell size, and macrophage and T-cell phenotypes.
Outcome Type:Primary Outcome
Measure:T cell receptor phenotypes
Time Frame:post-operatively (1-2 years status post bariatric surgery)
Safety Issues:False
Description:Frequency of T-cell receptors in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.
Outcome Type:Primary Outcome
Measure:T cell receptor phenotypes
Time Frame:(Timeframe: baseline (within 2 months prior to bariatric surgery)
Safety Issues:False
Description:Frequency of T-cell receptors in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.
Outcome Type:Primary Outcome
Measure:Macrophage phenotype
Time Frame:post-operatively (1-2 years status post bariatric surgery)
Safety Issues:False
Description:Frequency of macrophage phenotype (M1 vs M2) in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.
Outcome Type:Primary Outcome
Measure:Macrophage phenotype
Time Frame:(Timeframe: baseline (within 2 months prior to bariatric surgery)
Safety Issues:False
Description:Frequency of macrophage phenotype (M1 vs M2) in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.
Outcome Type:Primary Outcome
Measure:Adipose cell size associated with T cell profile and IR.
Time Frame:post-operatively (1-2 years status post bariatric surgery)
Safety Issues:False
Description:Cell size of subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.
Outcome Type:Primary Outcome
Measure:Adipose cell size associated with T cell profile and IR.
Time Frame:baseline (within 2 months prior to bariatric surgery)
Safety Issues:False
Description:Cell size of subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.
Outcome Type:Primary Outcome
Measure:T-cell profile in visceral and subcutaneous fat
Time Frame:post-operatively (1-2 years status post bariatric surgery)
Safety Issues:False
Description:Pro-inflammatory and anti-inflammatory T cell profiles in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.
Outcome Type:Primary Outcome
Measure:T-cell profile in visceral and subcutaneous fat
Time Frame:baseline (within 2 months prior to bariatric surgery)
Safety Issues:False
Description:Pro-inflammatory and anti-inflammatory T cell profiles in subcutaneous adipose tissue and visceral adipose tissue measured via flow cytometry.

Study Interventions

There are no available Study Interventions

Study Arms

Study Arm Type:Other
Arm Name:Bariatric Cohort
Description:For consenting subjects who are undergoing bariatric surgery, a visceral fat sample will be taken during surgery. In addition to the fat sample, insulin resistance will be measured and determined by a modification of the insulin suppression test.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Stanford University
Agency Class:Other
Agency Type:Collaborator
Agency Name:American Heart Association

Samples and Retentions

Sample Retention:Samples With DNA
Description: Visceral adipose tissue (VAT), Subcutaneous adipose tissue (SAT) and peripheral blood samples are obtained perioperatively.
Study Population: There are no restrictions in regards to gender, race, or socioeconomic status. The racial/ ethnic composition of the study population will be reflective of the communities surrounding the Stanford University Medical Center.
Sample Method:Non-Probability Sample

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: August 05, 2021

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


This study is not currently recruiting Study Participants. The form below is not enabled.