Adipocyte-Derived Extracellular Vesicles, Weight Loss, and Endothelial Function

NCT06776081 | Recruiting

• 2 other identifiers: 24-052324TPA1301309
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

Changes in adipose tissue biology are now recognized as a key factor underlying the increased risk of metabolic and cardiovascular disease with obesity. Clinical interest in adipocyte-derived extracellular vesicles (Ad-EVs) has intensified due to their potential as circulating biomarkers of adipose tissue health and systemic messengers, regulators and mediators of cardiometabolic health and disease with obesity. The investigators hypothesize that elevated Ad-EVs in adults with obesity will be negatively associated with endothelium-dependent vasodilation. Furthermore, the investigators hypothesize that in adults with obesity, intentional weight loss-induced reduction in circulating Ad-EVs is associated with greater endothelium-dependent vasodilation.

Conditions

Obesity; Weight Loss

Keywords

Obesity; Weight Loss

Outcome Measures

Primary Outcomes (6)

• Phase 1: Circulating adipocyte-derived extracellular vesicles (Ad-EVs)

  Circulating Ad-EVs will be determined from a peripheral blood sample in normal weight and obese adults. Ad-EVs will be determined using flow cytometry. The samples will be incubated with perilipin A. Ad-EVs will be defined as perilipin A positive cells ranging in size 0.2-0.8 um.

  Circulating Ad-EVs will measured during Phase 1 visit 2 which is ~2 weeks from their respective start date.

• Phase 2: Circulating adipocyte-derived extracellular vesicles (Ad-EVs)

  Circulating Ad-EVs will be determined from a peripheral blood sample following the obese participants 12-week weight loss intervention.

  Circulating Ad-EVs will be measured during Phase 2 visit 15 which is ~17 weeks from their respective start date.

• Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh)

  FBF is measured via strain-gauge venous occlusion plethysmography in response to saline for 5 minutes and then to ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min; the doses of ACh infused into the brachial artery) for 5 minutes at each dose. Flows during the last minute of saline and each drug dose are measured and the mean value reported.

  FBF response to ACh will be measured during Phase 1 and the participant's visit 2 which is ~ 2 weeks from their respective start date.

• Phase 2: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh)

  FBF is measured via strain-gauge venous occlusion plethysmography in response to saline for 5 minutes and then to ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min; the doses of ACh infused into the brachial artery) for 5 minutes at each dose. Flows during the last minute of saline and each drug dose are measured and the mean value reported.

  FBF response to ACh will be measured during Phase 2 and the participant's visit 15 which is ~17 weeks from their respective start date.

• Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP)

  FBF is measured via strain-gauge venous occlusion plethysmography in response to saline for 5 minutes and then to NTP (1.0, 2.0 and 4.0 ug/100 mL tissue/min; the doses of NTP infused into the brachial artery) for 5 minutes at each dose. Flows during the last minute of saline and each drug dose are measured and the mean value reported.

  FBF response to NTP will be measured during Phase 1 and the participant's visit 2 which is ~ 2 weeks from their respective start date.

• Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP)

  FBF is measured via strain-gauge venous occlusion plethysmography in response to saline for 5 minutes and then to NTP (1.0, 2.0 and 4.0 ug/100 mL tissue/min; the doses of NTP infused into the brachial artery) for 5 minutes at each dose. Flows during the last minute of saline and each drug dose are measured and the mean value reported.

  FBF response to NTP will be measured during Phase 2 and the participant's visit 15 which is ~17 weeks from their respective start date.

Study Arms (2)

No Intervention: Phase 1

NO INTERVENTION

Phase 1 is a cross-sectional study to compare whether circulating Ad-EVs are associated with obesity-related endothelial dysfunction in normal weight adults and adults with obesity.

Experimental: Phase 2

EXPERIMENTAL

Phase 2 employs an intervention study design, to determine in adults with obesity, the effects of intentional weight loss (12-weeks) on circulating Ad-EVs and their effect on endothelium-dependent vasodilation.

Other: Weight loss without pharmacotherapy

Interventions

Weight loss without pharmacotherapy OTHER

Adults with obesity participating in the 12-week hypocaloric diet-induced weight loss intervention will be individually counseled by the Clinical and Translational Research Center (CTRC) bionutritionist to consume a hypocaloric diet consistent with current dietary recommendations for weight loss until a 6-10% weight loss is achieved.

Experimental: Phase 2

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥40 years
• BMI \<25 kg/m2 and BMI \>25 kg/m2 for Phase 1 and BMI \>25 kg/m2 for Phase 2. Rationale for defining obesity as BMI \>25 kg/m2

You may not qualify if:

• Current smoker
• Chronic overt medical condition (e.g., evidence of coronary artery disease on resting ECG, any history of myocardial infarction or stroke, or cancer, diabetes based on fasting blood glucose concentration)
• Alcohol abuse or dependence defined as more than 14 standard drinks/week and no more than 4 standard drinks/day for men and 7 standard drinks/week and 3 standard drinks/day for women (a standard drink is defined as 12 ounces of beer, 5 ounces of wines, 1 ½ ounces of 80-proof distilled spirits) reported during the medical history/physical exam
• Stage III hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg)
• Regular vigorous aerobic/endurance exercise (\>3 bouts/week, \>30 minutes/bout at a workload \>6 METS)
• Women who are pregnant or breastfeeding
• History of anaphylaxis to betadine, lidocaine, iodine
• Raynaud's disease
• History of clotting disorders
• Anyone taking blood thinners and clotting medications
• Anyone taking statin medication
• Planned pregnancy in coming 4-6 months

Sponsors & Collaborators

• University of Colorado, Boulder: lead

Study Sites (1)

University of Colorado Boulder Clinical and Translational Research Center (CTRC)

Boulder, Colorado, 80309, United States

RECRUITING

MeSH Terms

Conditions

Obesity; Weight Loss

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Christopher DeSouza, PhD

  University of Colorado, Boulder

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jared Greiner, MS

CONTACT

303-735-3605; greinerj@colorado.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Distinction

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: January 15, 2025
• Study Start: July 1, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

US (1)