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Peripheral Vasodilation in Obese Humans (ObeseDilate)

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ClinicalTrials.gov Identifier: NCT02833207
Recruitment Status : Recruiting
First Posted : July 14, 2016
Last Update Posted : January 31, 2018
Sponsor:
Information provided by (Responsible Party):
University of Wisconsin, Madison

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.

Condition or disease Intervention/treatment Phase
Obesity Drug: Drug Trial 1 (EDD) Drug: Drug Trial 2 (ROV) Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Peripheral Vasodilation in Obese Humans
Study Start Date : July 2011
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : July 2018

Arm Intervention/treatment
Experimental: EDD Obese
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)

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.

Other Name: EDD

Experimental: EDD Lean
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)

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.

Other Name: EDD

Experimental: ROV Obese
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)

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.

Other Name: ROV

Experimental: ROV Lean
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)

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.

Other Name: ROV




Primary Outcome Measures :
  1. Change in limb blood flow in response to stimuli that cause vasodilation (ATP, ISO, BK, Ach, muscle contractions). [ Time Frame: Through study completion ]
    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.

  2. Change in limb blood flow in response to barium chloride infusion which inhibits potassium channel vasodilation. [ Time Frame: Through study completion ]
    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.


Secondary Outcome Measures :
  1. Endothelial cell collection from arterial catheter to measure protein expression. [ Time Frame: Through study completion ]
    Protein expression in endothelial cells harvested from arterial catheter that may be responsible for EDD or ROV functional changes (optional for subjects). Immunohistochemical methods will be used. Differences in protein expression will be assessed semi-quantitatively by normalizing expression to standard human endothelial cell cultures.

  2. Change in blood flow in response to L-NMMA and ketorolac in the presence of barium chloride [ Time Frame: Minutes/seconds between baseline and peak response to stimuli ]
    Change in limb blood flow (ml/min), measured with Doppler ultrasound, in response to L-NMMA and ketorolac infusion in the presence of barium chloride infusion. This will be calculated by taking the difference between the stimulus blood flow response and the stimulus blood flow response in the presence of all inhibitors (barium chloride, ketorolac, and L-NMAA). These changes will be compared between lean and obese.



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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Participation in vigorous aerobic exercise >90 minutes per week
  • Arterial structures in the arm that are not conducive to study in the laboratory setting
  • Females: Self-reported pregnancy and/or breastfeeding, diagnosed with polycystic ovarian syndrome, or without regular menses. Urine pregnancy test will be performed on study day to ensure subject is not pregnant on study day.
  • An abnormality or contraindication to study participation which is not covered in the eligibility criteria.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02833207


Locations
United States, Wisconsin
University of Wisconsin, Madison Recruiting
Madison, Wisconsin, United States, 53706
Contact: William G Schrage, PhD    608-262-7715    wschrage@wisc.edu   
Contact: Christina Sauder, MS    608-263-6308    cjsauder@wisc.edu   
Sponsors and Collaborators
University of Wisconsin, Madison
Investigators
Principal Investigator: William Schrage, Ph.D. UW Madison

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT02833207     History of Changes
Other Study ID Numbers: 2011-0199
First Posted: July 14, 2016    Key Record Dates
Last Update Posted: January 31, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by University of Wisconsin, Madison:
blood flow
vasodilation
Doppler Ultrasound
endothelium dependent dilation