Role of Adiposomes in Endothelial Dysfunction

NCT05199454 | Recruiting

• 2 other identifiers: 2021-11131R01HL161386-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The development of type II diabetes (T2D) is strongly associated with obesity and both are well-established risk factors for cardiovascular disease. Knowing that vascular dysfunction is an early event in the development of cardiovascular disease in obese diabetic (OB-T2D) patients, The investigators set their long-term goal to define molecular mechanisms of vascular dysfunction and corrective strategies that target these mechanisms such as physical activity and weight loss. The investigators recently discovered that human adipose tissues release extracellular vesicles (adiposomes) that are efficiently captured by endothelial cells. Adiposomes are known to carry bioactive cargos such as proteins and micro RNAs; however, their lipid content has not been studied nor has their ability to transfer their lipid cargo to endothelial cells. In the current application, the investigators propose to investigate the role of adiposomes in communicating the unhealthy milieu, mainly dysregulated lipids, to endothelial cells in OB-T2D subjects. On top of these lipid species that the investigators propose to be carried by adiposomes are glycosphingolipids (GSLs). These lipids originate from the glycosylation of ceramides, a chemical process that is upregulated in the presence of inflammation and high glucose levels. Preliminary findings showed that in endothelial cells, GSL-rich adiposomes disturb plasma membrane structure and subsequently induce endothelial dysfunction. Moreover, the investigators found that preconditioning endothelial cells with high shear stress (which is an exercise mimetic) protected endothelial cells from the detrimental effects induced by adiposomes. Therefore, the central hypothesis is that adipose tissues in OB-T2D patients release GSL-loaded adiposomes that induce vascular endothelial dysfunction. The researchers propose that exercise and weight loss interventions (bariatric surgery) will restore adipose tissue homeostasis, reduce GSL-loaded adiposomes, and subsequently alleviate vascular risk in OB-T2D patients. The investigators will test the hypotheses by pursuing the following aims: aim 1: Investigate the role of GSL-rich adiposomes in the pathogenesis of endothelial dysfunction in OB-T2D adults; aim 2: Test the effectiveness of exercise training in reducing adiposome-mediated effects on vascular function; and aim 3: Examine changes in adiposome/caveolae axis following metabolic surgery and their association with vascular function.

Conditions

Obesity; Diabetes; Cardiovascular Diseases

Outcome Measures

Primary Outcomes (1)

• Brachial artery flow-mediated dilation (percent vasodilation) in 60 obese diabetic subjects

  Brachial flow-mediated dilation will be measured using ultrasound Alpha 7. For recording, a linear probe will be positioned five centimeters above the left arm's antecubital fossa, and a 1-minute baseline imaging will be recorded. Then, a blood pressure cuff will be put around the right mid-forearm and inflated to 200 to 220 mmHg for 5 minutes. Following cuff deflation (reactive hyperemia), a video grabber will be used to record a 300-second video sequence at three frames per second for offline measurement. The greatest brachial artery diameter at baseline will be deducted from the largest mean values obtained following cuff deflation to determine relative flow mediated dilation

  4 years

Secondary Outcomes (1)

• Glycosphingolipid content (ng/ml) in adiposomes from 60 obese diabetic subjects

  4 years

Study Arms (2)

Exercise training

EXPERIMENTAL

Aerobic exercise training for 12 weeks, 3 times per week, 60 minutes per session.

Other: Exercise training

Control (standards of care)

NO INTERVENTION

This arm will receive brochures for healthy lifestyle recommendations. No intervention will be conducted.

Interventions

Exercise training OTHER

Aerobic exercise training using a treadmill or a bike for 12 weeks, 3 times per week, 60 minutes per session.

Exercise training

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• BMI ≥ 35 kg/m2
• Between ages 18-50 years
• Not pregnant
• Diabetic (Current use of diabetes medication or fasting glucose ≥126 mg/dL)
• Medical clearance to participate in a moderate-intensity exercise program

You may not qualify if:

• Pregnant women
• Current smokers
• Currently abusing alcohol or drugs
• Chronic heart, liver, or kidney diseases, autoimmune diseases, or cancer
• Non-English speakers
• History of allergic reactions to lidocaine

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

RECRUITING

MeSH Terms

Conditions

Obesity; Diabetes Mellitus; Cardiovascular Diseases

Interventions

Exercise

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Abeer M Mohamed, MD, PhD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abeer M Mohamed, MD, PhD

CONTACT

312-355-8099; amahmo4@uic.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Randomized Clinical Trial

Study Record Dates

• First Submitted: December 19, 2021
• First Posted: January 20, 2022
• Study Start: May 16, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)