P1A3B: Characterization of Brachial Arterial t-PA Release, Endothelial Function, Obesity and Inflammation

• Sponsor: Vanderbilt University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00780481
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Arm: 1
• Actual Duration (Months): 51.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

T-PA release is impaired in obese subjects. In order to have a better mechanistic understanding of t-PA release, we will compare t-PA release to Flow Mediated Vasodilation, Radial Artery Tonometry, and other markers of endothelial function and oxidative stress.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Bradykinin	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Characterization of Brachial Arterial t-PA Release, Vasodilator Function, and Vascular Compliance and Correlation With Fibrinolytic Balance, Oxidative Stress, and Inflammation Measures (SCCOR Project 1 Aim 3B)
• Actual Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bradykinin Patients will have flow mediated vasodilation and radial artery tonometry performed. They will then receive 0, 10, 20, 40 ng/100cc/min of intrabrachial bradykinin. Strain gauge plethysmography and blood sampling at each dose will be done to evaluate t-PA release. Blood will also be drawn for other biomarkers.	Drug: Bradykinin; Intrabrachial - 0, 10, 20, 40 ng/100cc/min over 5 minutes at each dose.

Outcome Measures

Primary Outcome Measures

1. Peak t-PA Release [Single Study day]

   tPA Release

Secondary Outcome Measures

1. Peak FMD [Single Study Day]

2. Radial Artery Elasticity [Single Study Visit]

3. Lipid Levels, PAI-1 Levels, CRP Levels, F2 Isoprostanes and Other Biomarkers of Inflammation and Obesity. [Single Study Day]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

1. Adults 18 years and greater

2. Healthy

Exclusion criteria:

1. PVC < 30

2. Hypertensive subjects on ACE inhibitors

3. Pregnant or nursing mothers

4. Diabetic with HbA1C > 7.5 or stigmata of end organ damage (neuropathy, retinopathy, nephropathy, cardiomyopathy)

5. Cholesterol > 30 mg/dL above NCEP accepted level based on cardiac risk.

6. Triglycerides > 200

7. Previously diagnosed obstructive coronary artery disease, myocardial infarction or left ventricular dysfunction (with or without a history of congestive heart failure)

8. Renal insufficiency (Creatinine ≥ 1.5 mg/dl)

9. History of cerebrovascular disease

10. Any chronic inflammatory disease (rheumatologic, inflammatory bowel disease, etc)

11. Uncontrolled Stage 2 Hypertension (160/100 mmHg), or end organ damage due to hypertension (left ventricular hypertrophy, atrial fibrillation, hematuria, renal insufficiency, prior cerebrovascular disease).

12. Angiotensin converting enzyme inhibitor use

13. Coagulopathy (INR ≥ 1.5, PTT ≥ 1.5 x control)

14. Other chronic medical illnesses at the discretion of the investigators

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University

Investigators

• Principal Investigator: James AS Muldowney, MD, Vanderbilt University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: James Muldowney, Assistant Professor of Medicine, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00780481
• Other Study ID Numbers: 061160
• First Posted: Oct 27, 2008
• Last Update Posted: Jul 14, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by James Muldowney, Assistant Professor of Medicine, Vanderbilt University: Obesity; Endothelial Function; Fibrinolytic Balance; Baseline
• Additional relevant MeSH terms: Obesity; Inflammation; Bradykinin; Kininogens

Study Results

Participant Flow

Pre-assignment Detail	The data for this study was lost. The total number of participants enrolled/completed was pulled from IRB records. Participant age was between 18-65 per protocol. All participants were enrolled in the United States. No other data is available

Arm/Group Title	Bradykinin
Arm/Group Description	Patients will have flow mediated vasodilation and radial artery tonometry performed. They will then receive 0, 10, 20, 40 ng/100cc/min of intrabrachial bradykinin. Strain gauge plethysmography and blood sampling at each dose will be done to evaluate t-PA release. Blood will also be drawn for other biomarkers. Bradykinin: Intrabrachial - 0, 10, 20, 40 ng/100cc/min over 5 minutes at each dose.
Period Title: Overall Study
STARTED	13
COMPLETED	13
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Bradykinin
Arm/Group Description	Patients will have flow mediated vasodilation and radial artery tonometry performed. They will then receive 0, 10, 20, 40 ng/100cc/min of intrabrachial bradykinin. Strain gauge plethysmography and blood sampling at each dose will be done to evaluate t-PA release. Blood will also be drawn for other biomarkers. Bradykinin: Intrabrachial - 0, 10, 20, 40 ng/100cc/min over 5 minutes at each dose.
Overall Participants	13
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female
Male
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Peak t-PA Release
Description	tPA Release
Time Frame	Single Study day

Outcome Measure Data

Analysis Population Description

Data was lost

Arm/Group Title	Bradykinin
Arm/Group Description	Patients will have flow mediated vasodilation and radial artery tonometry performed. They will then receive 0, 10, 20, 40 ng/100cc/min of intrabrachial bradykinin. Strain gauge plethysmography and blood sampling at each dose will be done to evaluate t-PA release. Blood will also be drawn for other biomarkers. Bradykinin: Intrabrachial - 0, 10, 20, 40 ng/100cc/min over 5 minutes at each dose.
Measure Participants	0

2. Secondary Outcome

Title	Peak FMD
Time Frame	Single Study Day

Outcome Measure Data

Analysis Population Description

Data Lost

Arm/Group Title	Bradykinin
Arm/Group Description	Patients will have flow mediated vasodilation and radial artery tonometry performed. They will then receive 0, 10, 20, 40 ng/100cc/min of intrabrachial bradykinin. Strain gauge plethysmography and blood sampling at each dose will be done to evaluate t-PA release. Blood will also be drawn for other biomarkers. Bradykinin: Intrabrachial - 0, 10, 20, 40 ng/100cc/min over 5 minutes at each dose.
Measure Participants	0

3. Secondary Outcome

Title	Radial Artery Elasticity
Time Frame	Single Study Visit

Outcome Measure Data

Analysis Population Description

Data was lost

Arm/Group Title	Bradykinin
Arm/Group Description	Patients will have flow mediated vasodilation and radial artery tonometry performed. They will then receive 0, 10, 20, 40 ng/100cc/min of intrabrachial bradykinin. Strain gauge plethysmography and blood sampling at each dose will be done to evaluate t-PA release. Blood will also be drawn for other biomarkers. Bradykinin: Intrabrachial - 0, 10, 20, 40 ng/100cc/min over 5 minutes at each dose.
Measure Participants	0

4. Secondary Outcome

Title	Lipid Levels, PAI-1 Levels, CRP Levels, F2 Isoprostanes and Other Biomarkers of Inflammation and Obesity.
Time Frame	Single Study Day

Outcome Measure Data

Analysis Population Description

Data was lost

Arm/Group Title	Bradykinin
Arm/Group Description	Patients will have flow mediated vasodilation and radial artery tonometry performed. They will then receive 0, 10, 20, 40 ng/100cc/min of intrabrachial bradykinin. Strain gauge plethysmography and blood sampling at each dose will be done to evaluate t-PA release. Blood will also be drawn for other biomarkers. Bradykinin: Intrabrachial - 0, 10, 20, 40 ng/100cc/min over 5 minutes at each dose.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	All data for this study was lost. Unable to provide any information on adverse events.
Arm/Group Title	Bradykinin
Arm/Group Description	Patients will have flow mediated vasodilation and radial artery tonometry performed. They will then receive 0, 10, 20, 40 ng/100cc/min of intrabrachial bradykinin. Strain gauge plethysmography and blood sampling at each dose will be done to evaluate t-PA release. Blood will also be drawn for other biomarkers. Bradykinin: Intrabrachial - 0, 10, 20, 40 ng/100cc/min over 5 minutes at each dose.
All Cause Mortality
	Bradykinin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bradykinin
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Bradykinin
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.