Peripheral Vasodilation in Obese Humans

NCT02833207 | Terminated Phase 1 DMC FDA Drug

• 5 other identifiers: 2011-0199A176000EDUC\KINESIOLOGY\KINESIOR01HL105820Protocol Version 4/27/2021
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The growing population of obese adults is predicted to create a large public health burden in the next few decades. This study examines function of small blood vessels providing blood flow to skeletal muscles, to test if younger obese individuals (≤40 years old, BMI \>30) are already displaying reductions in blood vessel function. This study will test if the signals blood vessels use to increase blood flow are changing in these same subjects. Findings from this study may help create treatments to delay or prevent some of the negative effects of obesity on vascular health.

Conditions

Obesity

Keywords

blood flow; vasodilation; Doppler Ultrasound; endothelium dependent dilation

Outcome Measures

Primary Outcomes (2)

• Change in limb blood flow in response to stimuli that cause vasodilation (ATP, ISO, BK, Ach, muscle contractions).

  Change in limb blood flow (ml/min), measured with Doppler ultrasound, in response potassium vasodilation (EDD or ROV). The change in blood flow will be calculated by taking the difference between the stimulus blood flow response and the baseline blood flow. These changes will be compared between lean and obese.

  Through study completion

• Change in limb blood flow in response to barium chloride infusion which inhibits potassium channel vasodilation.

  Change in limb blood flow (ml/min), measured with Doppler ultrasound, in response to barium chloride infusion (inhibition of K+ vasodilation). This will be calculated by taking the difference between the stimulus blood flow response and the stimulus blood flow response in the presence of barium chloride. These changes will be compared between lean and obese.

  Through study completion

Secondary Outcomes (2)

• Endothelial cell collection from arterial catheter to measure protein expression.

  Through study completion

• Change in blood flow in response to L-NMMA and ketorolac in the presence of barium chloride

  Minutes/seconds between baseline and peak response to stimuli

Study Arms (4)

EDD Obese

EXPERIMENTAL

On study visit after screening. Brachial artery catheter in the non-dominant arm + infusion drugs (IND approval) to test basic vascular function and associated mechanisms in healthy volunteers. Eligible obese subjects will undergo Drug Trial 1 (EDD) (described in Intervention section).

Drug: Drug Trial 1 (EDD)

EDD Lean

EXPERIMENTAL

On study visit after screening. Brachial artery catheter in the non-dominant arm + infusion drugs (IND approval) to test basic vascular function and associated mechanisms in healthy volunteers. Eligible lean subjects will undergo Drug Trial 1 (EDD) (described in Intervention section).

Drug: Drug Trial 1 (EDD)

ROV Obese

EXPERIMENTAL

On study visit after screening. Brachial artery catheter in the non-dominant arm + infusion drugs (IND approval) to test basic vascular function and associated mechanisms in healthy volunteers. Eligible obese subjects will undergo Drug Trial 2 (ROV) (described in Intervention section).

Drug: Drug Trial 2 (ROV)

ROV Lean

EXPERIMENTAL

On study visit after screening. Brachial artery catheter in the non-dominant arm + infusion drugs (IND approval) to test basic vascular function and associated mechanisms in healthy volunteers. Eligible lean subjects will undergo Drug Trial 2 (ROV) (described in Intervention section).

Drug: Drug Trial 2 (ROV)

Interventions

Drug Trial 1 (EDD) DRUG

Drugs that increase blood flow and test EDD are: ACh, ISO, BK, ATP. Remaining drugs used to test mechanisms of EDD: L-NMMA, ketorolac, and BaCl2. Details under study description.

Also known as: EDD

EDD Lean; EDD Obese

Drug Trial 2 (ROV) DRUG

Tools used to increase blood flow: muscle contractions and ATP. Remaining drugs used to test mechanisms of ROV: L-NMMA, ketorolac, and BaCl2. Details under study description.

Also known as: ROV

ROV Lean; ROV Obese

Eligibility Criteria

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

You may qualify if:

• Age: ≥18 - ≤ 40 years of age
• Blood pressure systolic ≤125 and diastolic ≤85 mmHg (Lean control) and \<140 and diastolic \<90 mmHg (Obese subjects)
• BMI \<25 kg/m2 (Lean control) and ≥30 kg/m2 (Obese subjects)
• Fasting blood glucose \<100 mg/dL
• Fasting LDL \<130 mg/dL
• Fasting blood triglycerides \<150 mg/dL
• Females: Premenopausal with a regular menstrual cycle. Negative pregnancy test. Note: Must be studied in the early follicular phase (day 1-5) of their menstrual cycle or the low hormone phase of oral contraceptive use.

You may not qualify if:

• Specific to obese subjects only (to exclude obese subjects with metabolic syndrome):
• a. If Systolic BP 130 ≤ BP \< 140 mmHg or Diastolic BP 85 ≤ BP \< 90 mmHg i. HDL \< 40 mg/dL for men ii. HDL \< 50 mg/dL for women
• Increased risk of bleeding
• Sensitivity to lidocaine
• Procoagulant or other clotting disorders
• Taking cardiovascular medications (anti-hypertensives, statins, platelet inhibitors, etc.) or metabolic medications (insulin-sensitizing)
• Regularly (≥5 days/week) take acetylsalicylic acid and/or non-steroidal anti-inflammatory drugs (NSAIDs)
• Self-reported current diagnosis of exhibiting obstructive sleep apnea
• Self-reported current or past diagnosis of diabetes
• Self-reported history of peripheral vascular disease
• Self-reported history of hepatic disease
• Self-reported history of renal disease
• Self-reported history of hematologic disease
• Self-reported history of stroke
• Current use of tobacco (i.e. smoke, smokeless, and vapor). Prior tobacco use with \>1 year abstaining is allowed.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Wisconsin, Madison

Madison, Wisconsin, 53706, United States

Location

MeSH Terms

Conditions

Obesity; Aneurysm

Interventions

UBR5 protein, human

Condition Hierarchy (Ancestors)

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

Study Officials

• William Schrage, Ph.D.

  UW Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2016
• First Posted: July 14, 2016
• Study Start: April 16, 2012
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: February 11, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)