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Trial record 37 of 221 for:    Aldosterone

Renin-Angiotensin Aldosterone System and Fibrinolysis Interaction in Humans-Specific Aim 3

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ClinicalTrials.gov Identifier: NCT00685945
Recruitment Status : Completed
First Posted : May 29, 2008
Results First Posted : February 25, 2013
Last Update Posted : February 25, 2013
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Center for Research Resources (NCRR)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Single (Participant);   Primary Purpose: Health Services Research
Condition Obesity
Interventions Drug: Control (bradykinin)
Drug: L-NMMA + bradykinin
Drug: Isosorbide + L-NMMA + bradykinin
Drug: Sildenafil + L-NMMA + bradykinin
Enrollment 24
Recruitment Details Subjects were recruited from a volunteer registry at Vanderbilt University. Subjects who participated in prior studies and requested to be contacted for future studies were included in the recruitment process. Recruitment began on 12/07 and stopped on 1/09.
Pre-assignment Details Subjects with renal, endocrine, hematological or cardiovascular disease (including hypertension defined as an untreated systolic/diastolic blood pressure greater than 140/90 mmHg were excluded. Subjects with a fasting cholesterol greater than 5.7 mmol/L (220 mg/dl) and smokers were excluded. No washout period was required for the study.
Arm/Group Title All Participants
Hide Arm/Group Description 24 subjects received a bradykinin infusion and then a bradykinin + L-NMMA infusion. Subjects were then randomized to receive either isosorbide (N=12) or sildenafil (N=12). The infusion of bradykinin + L-NMMA was then repeated.
Period Title: Control (Bradykinin Infusion)
Started 24 [1]
Completed 24
Not Completed 0
[1]
A total of 24 subjects received an infusion of bradykinin
Period Title: L-NMMA + Bradykinin
Started 24
Completed 23
Not Completed 1
Reason Not Completed
Physician Decision             1
Period Title: Isosorbide + L-NMMA + Bradykinin
Started 11
Completed 11
Not Completed 0
Period Title: Sildenafil + L-NMMA + Bradykinin
Started 12
Completed 12
Not Completed 0
Arm/Group Title All Participants
Hide Arm/Group Description Subjects characteristics for all 24 participants
Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
<=18 years
0
   0.0%
Between 18 and 65 years
24
 100.0%
>=65 years
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
31.71  (6.51)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
12
  50.0%
Male
12
  50.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 24 participants
24
1.Primary Outcome
Title Net Tissue-type Plasminogen Activator (t-PA) Release
Hide Description Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively.
Time Frame During and after each study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Twenty four subjects were studied. One subject was excluded because of erroneous drug administration. Analysis was per protocol. Twenty-three subjects receive bradykinin then L-NMMA plus bradykinin infusions. Subjects were then randomized to either isosorbide or sildenafil. Twelve subjects received sildenafil and 11 subjects received isosorbide.
Arm/Group Title Control L-NMMA + Control Isosorbide + L-NMMA + Control Sildenafil + L-NMMA + Control
Hide Arm/Group Description:
Subjects received bradykinin at 50, 100 and 200ng/min
After the intial bradykinin infusion subjects then received a continuous infusion of L-NMMA plus bradykinin at 50, 100 and 200ng/min
Eleven of the twenty-four subjects were randomized to isosorbide after completing the bradykinin and bradykinin plus L-NMMA infusions. The bradykinin plus L-NMMA infusions were then repeated.
Twelve of the twenty-four subjects were randomized to sildenafil after completing the bradykinin and bradykinin plus L-NMMA infusions. After 1 hour, bradykinin plus L-NMMA infusions were repeated.
Overall Number of Participants Analyzed 24 23 11 12
Mean (Standard Error)
Unit of Measure: ng/min/100ml
Net t-PA release (bradykinin 0ng/min) 0.24  (0.39) 0.59  (0.23) -0.38  (0.51) 0.29  (0.67)
Net t-PA release (bradykinin 50ng/min) 1.02  (1.06) 3.65  (0.79) 3.14  (1.13) 2.46  (2.07)
Net t-PA release (bradykinin 100ng/min) 11.81  (2.12) 22.10  (5.51) 15.90  (3.13) 18.48  (9.11)
Net t-PA release (bradykinin 200ng/min) 30.03  (4.24) 39.90  (6.98) 45.32  (9.45) 37.39  (11.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control, L-NMMA + Control, Isosorbide + L-NMMA + Control, Sildenafil + L-NMMA + Control
Comments The effect of bradykinin on net t-PA release was determined using general linear model-repeated measures ANOVA in which the between-subject variable was gender, and the within-subjects variables were drug (control, +L-NMMA, +L-NMMA plus isosorbide, or +L-NMMA plus sildenafil) and dose of bradykinin.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
2.Secondary Outcome
Title Forearm Blood Flow (FBF)
Hide Description Forearm blood flow was measured by strain gauge plethysmography
Time Frame During and after each study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control L-NMMA + Control Isosorbide + L-NMMA + Control Sildenafil + L-NMMA + Control
Hide Arm/Group Description:
Subjects received bradykinin at 50, 100 and 200ng/min
Subjects received a continuous infusion of L-NMMA plus bradykinin at 50, 100 and 200ng/min
Twelve (of the twenty-four)subjects received isosorbide after completing the bradykinin and bradykinin plus L-NMMA infusions. The bradykinin plus L-NMMA infusions were then repeated.
Twelve (of the twenty-four) subjects received sildenafil after completing the bradykinin and bradykinin plus L-NMMA infusions. After 1 hour, bradykinin plus L-NMMA infusions were repeated.
Overall Number of Participants Analyzed 24 23 11 12
Mean (Standard Error)
Unit of Measure: ml/min/100ml
FBF (bradykinin 0 ng/min) 4.03  (0.25) 2.36  (0.18) 2.18  (0.33) 2.80  (0.37)
FBF (bradykinin 50ng/min) 7.02  (0.57) 5.16  (0.37) 4.73  (0.70) 5.87  (0.79)
FBF (bradykinin 100ng/min) 13.17  (1.04) 8.67  (0.81) 6.83  (1.13) 9.13  (0.76)
FBF (bradykinin 200 ng/min) 17.74  (1.43) 11.21  (1.12) 9.91  (1.72) 12.92  (1.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control, L-NMMA + Control, Isosorbide + L-NMMA + Control, Sildenafil + L-NMMA + Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments Repeated measures ANOVA
3.Other Pre-specified Outcome
Title Net Glucose Uptake
Hide Description Individual net reuptake rates at each time point were calculated by the following formula: net uptake = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of glucose in the brachial vein and artery, respectively.
Time Frame At baseline and after maximum dose of bradykinin
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control L-NMMA + Control Isosorbide + L-NMMA + Control Sildenafil + L-NMMA + Control
Hide Arm/Group Description:
Subjects received bradykinin at 50, 100 and 200ng/min
Subjects received a continuous infusion of L-NMMA plus bradykinin at 50, 100 and 200ng/min
Twelve (of the twenty-four)subjects received isosorbide after completing the bradykinin and bradykinin plus L-NMMA infusions. The bradykinin plus L-NMMA infusions were then repeated.
Twelve (of the twenty-four) subjects received sildenafil after completing the bradykinin and bradykinin plus L-NMMA infusions. After 1 hour, bradykinin plus L-NMMA infusions were repeated.
Overall Number of Participants Analyzed 24 23 11 12
Mean (Standard Error)
Unit of Measure: microgram/min/100ml
Net glucose uptake (bradykinin 0 ng/min) -79.95  (22.894) -74.36  (7.125) -71.4  (27.74) -67.3  (13.17)
Net glucose uptake (bradykinin 200 ng/min) -319.85  (97.109) -142.86  (49.935) -163.233  (36.504) -125.32  (45.705)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Participants
Hide Arm/Group Description Subjects characteristics for all 24 participants
All-Cause Mortality
All Participants
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
All Participants
Affected / at Risk (%) # Events
Total   0/24 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
All Participants
Affected / at Risk (%) # Events
Total   4/24 (16.67%)    
Nervous system disorders   
Headache   2/24 (8.33%)  2
fainted   1/24 (4.17%)  1
Vascular disorders   
unexpected drug response   1/24 (4.17%)  1
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Mias Pretorius
Organization: Vanderbilt University
Phone: 615-343-0665
EMail: mias.pretorius@vanderbilt.edu
Layout table for additonal information
Responsible Party: Nancy J. Brown, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00685945     History of Changes
Other Study ID Numbers: RAAS & Fibrinolysis
2R01HL060906 ( U.S. NIH Grant/Contract )
HL065193 ( Other Grant/Funding Number: NIH )
UL1RR024975 ( U.S. NIH Grant/Contract )
5R01HL085740-05 ( U.S. NIH Grant/Contract )
First Submitted: May 27, 2008
First Posted: May 29, 2008
Results First Submitted: August 25, 2011
Results First Posted: February 25, 2013
Last Update Posted: February 25, 2013