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

• ClinicalTrials.gov Identifier: NCT05833217
• Recruitment Status: Not yet recruiting
• First Posted: April 27, 2023
• Last Update Posted: May 1, 2023
• Sponsor: Stanford University
• Information provided by (Responsible Party): Tracey McLaughlin, Stanford University

Tracking Information

• First Submitted Date: April 26, 2023
• First Posted Date: April 27, 2023
• Last Update Posted Date: May 1, 2023
• Estimated Study Start Date: May 2, 2023
• Estimated Primary Completion Date: May 2, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 27, 2023)

• Triglyceride/HDL-cholesterol ratio [ Time Frame: 2 years ]
  Investigate the relationship between insulin resistance, as described by triglyceride/HDL-cholesterol ratio, and incident PASC (long COVID).
• Concentration of Viral RNA in Adipose Tissue [ Time Frame: 2 years ]
  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.
• Rate of Inflammatory Response [ Time Frame: 2 years ]
  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.
• Rate of Inflammatory Gene Expression in Adipose Tissue [ Time Frame: 2 years ]
  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.

Original Primary Outcome Measures (submitted: April 26, 2023)

• Triglyceride/HDL-cholesterol ratio in Long-COVID [ Time Frame: 2 years ]
  Investigate the relationship between insulin resistance, as described by triglyceride/HDL-cholesterol ratio, and incident PASC (long COVID).
• Viral RNA expression profile in Long-COVID Adipose Tissue [ Time Frame: 2 years ]
  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.
• Inflammatory Response Profile [ Time Frame: 2 years ]
  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.
• Inflammatory Gene Expression Profile in Long-COVID Adipose Tissue [ Time Frame: 2 years ]
  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.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Obesity, Insulin Resistance, and PASC: Persistent SARS-CoV-2
• Official Title: Obesity, Insulin Resistance, and PASC: Persistent SARS-CoV-2 Infection and Inflammation in Human Adipose Tissue
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Long COVID
• Insulin Resistance
• Insulin Sensitivity

Intervention

• 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 Name: Insulin Sensitivity Test

Study Arms

• 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.
  Intervention: Procedure: Adipose Tissue Biopsy
• Experimental: Healthy Controls Only

  We are looking for 20 healthy controls for 2 in-person visits on separate days.

  1. An Insulin Sensitivity Test (SSPG: Steady State Plasma Glucose) is performed to determine if the participant is insulin-sensitive or insulin resistant.
  2. 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.
  Interventions:

  • Procedure: Adipose Tissue Biopsy
  • Diagnostic Test: Steady State Plasma Glucose (SSPG) Test

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: April 26, 2023): 55
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2025
• Estimated Primary Completion Date: May 2, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Nicole Turk, BS; 6508880144; nturk@stanford.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05833217
• Other Study ID Numbers: 69063
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Tracey McLaughlin, Stanford University
• Original Responsible Party: Same as current
• Current Study Sponsor: Stanford University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Stanford University
• Verification Date: April 2023