Obesity, Insulin Resistance, and PASC: Persistent SARS-CoV-2

Obesity, Insulin Resistance, and PASC: Persistent SARS-CoV-2 Infection and Inflammation in Human Adipose Tissue

The investigators are studying the pathophysiologic links between obesity, insulin resistance (IR), adipose tissue infection, and post-acute sequelae of COVID-19 (PASC). This study looks at whether adipose (fat) tissue contributes to PASC by driving chronic inflammation or by serving as a reservoir for SARS-CoV-2 persistence. The results will not only determine whether obesity and IR are risk factors for PASC, but will also define fundamental biology that sets the stage for the investigation of novel or existing therapies that target the causal pathways identified.

Study Overview

• Status: Recruiting
• Conditions: Insulin Resistance; Insulin Sensitivity; Long COVID
• Intervention / Treatment: Procedure: Adipose Tissue Biopsy; Diagnostic test: Steady State Plasma Glucose (SSPG) Test

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicole Turk, BS; Phone Number: 6508880144; Email: nturk@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Enrolling by invitation
      • Clinical and Translational Research Unit
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Stanford Health
      • Contact: Nicole Turk, BS; Phone Number: 650-888-0144; Email: nturk@stanford.edu
      • Principal Investigator: Tracey McLaughlin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Ages 18 to 80
• BMI ≥ 25 kg/m2
• not currently pregnant

Exclusion Criteria:

Arm 2 (Adipose Tissue Biopsy) exclusions include

• pregnancy
• prior liposuction
• recent change in weight (> 2 kg in one month)
• bleeding disorders
• anticoagulant use

Arm 3 (healthy controls only) exclusions include patients with

• major organ disease
• diabetes
• history of liposuction
• bariatric surgery
• eating disorders
• psychiatric disorders
• pregnancy or lactation
• recent change in weight (over the past 12 weeks),
• use of weight loss medication or oral steroids
• hematocrit < 33%
• fasting glucose >= 126 mg/dL
• blood pressure >160/100 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Chart Review (not actively recruiting); Chart review of previously consented participants from the entire NIH RECOVER cohort, comprised of 15,000 infected and 2,600 noninfected patients across the country.
Experimental: COVID infected and healthy controls; Participants will perform a needle fat biopsy for tissue harvesting in the subacute phase (15-30d) of Covid-19 infection or as a healthy control. Our goal is 20 COVID-19 infected participants and 10 healthy controls.	Procedure: Adipose Tissue Biopsy; After an overnight fast, approximately 1-2 grams of subcutaneous fat will be removed by a needle. Participants will have a local anesthetic prior to the procedure. The needle fat biopsy will be repeated at quarterly intervals for one year (every 3 months). We will also draw 1 10mL tube of blood at each biopsy for measurement of inflammatory cytokines.
Experimental: Healthy Controls Only; We are looking for 20 healthy controls for 2 in-person visits on separate days.; An Insulin Sensitivity Test (SSPG: Steady State Plasma Glucose) is performed to determine if the participant is insulin-sensitive or insulin resistant.; A Needle Fat Biopsy: After an overnight fast, approximately 1-2 grams of subcutaneous fat will be removed by a needle. Patients will have a local anesthetic prior to the procedure.	Procedure: Adipose Tissue Biopsy; After an overnight fast, approximately 1-2 grams of subcutaneous fat will be removed by a needle. Participants will have a local anesthetic prior to the procedure. The needle fat biopsy will be repeated at quarterly intervals for one year (every 3 months). We will also draw 1 10mL tube of blood at each biopsy for measurement of inflammatory cytokines.; Diagnostic test: Steady State Plasma Glucose (SSPG) Test; An Insulin Sensitivity Test (SSPG: Steady State Plasma Glucose) is performed to determine if participants are insulin sensitive or insulin resistant. This test is approximately 5-6 hours in length. Participants will be asked to fast for 12 hours. The insulin sensitivity test is designed to measure how well your cells remove glucose from your blood in response to insulin. During this test participants will have two small catheters (tubing) placed in their veins (I.V. lines). The total amount of blood that will be drawn during this test will be 140 mL of blood (approximately 9.5 tablespoons). Insulin is a natural hormone, and octreotide (a synthetic hormone) is a drug that temporarily blocks the secretion of insulin from your pancreas. A member of the research team is present and monitoring the results along with the nursing staff.; Other Names: Insulin Sensitivity Test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Triglyceride/HDL-cholesterol ratio	Investigate the relationship between insulin resistance, as described by triglyceride/HDL-cholesterol ratio, and incident PASC (long COVID).	2 years
Concentration of Viral RNA in Adipose Tissue	Investigate the expression of viral RNA in adipose tissue in response to COVID-19 infection. Compare adipose tissue transcripts such as known MODY transcription factors measured by PCR between COVID-19 infected participants and healthy controls.	2 years
Rate of Inflammatory Response	Investigate inflammatory response to PPARgamma agonist (drug) and other compounds tested in vitro in human fat cells. 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.	2 years
Rate of Inflammatory Gene Expression in Adipose Tissue	Investigate the expression of inflammatory genes in adipose tissue in response to COVID-19 infection. Compare adipose tissue transcripts such as defensin chemokine receptors and platelet activation factors measured by PCR between COVID-19 infected participants and healthy controls.	2 years

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Tracey McLaughlin, MD, Stanford School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2023
• Primary Completion (Estimated): May 2, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: April 26, 2023
• First Submitted That Met QC Criteria: April 26, 2023
• First Posted (Actual): April 27, 2023

Study Record Updates

• Last Update Posted (Estimated): December 4, 2024
• Last Update Submitted That Met QC Criteria: December 2, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Insulin Resistance; Physiological Effects of Drugs; Hypoglycemic Agents; Insulin
• Other Study ID Numbers: 69063

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No