Trial Outcomes & Findings for Renin-Angiotensin Aldosterone System and Fibrinolysis Interaction in Humans-Specific Aim 3 (NCT NCT00685945)
NCT ID: NCT00685945
Last Updated: 2013-02-25
Results Overview
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.
COMPLETED
NA
24 participants
During and after each study drug administration
2013-02-25
Participant Flow
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.
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.
Participant milestones
| Measure |
All Participants
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.
|
|---|---|
|
Control (Bradykinin Infusion)
STARTED
|
24
|
|
Control (Bradykinin Infusion)
COMPLETED
|
24
|
|
Control (Bradykinin Infusion)
NOT COMPLETED
|
0
|
|
L-NMMA + Bradykinin
STARTED
|
24
|
|
L-NMMA + Bradykinin
COMPLETED
|
23
|
|
L-NMMA + Bradykinin
NOT COMPLETED
|
1
|
|
Isosorbide + L-NMMA + Bradykinin
STARTED
|
11
|
|
Isosorbide + L-NMMA + Bradykinin
COMPLETED
|
11
|
|
Isosorbide + L-NMMA + Bradykinin
NOT COMPLETED
|
0
|
|
Sildenafil + L-NMMA + Bradykinin
STARTED
|
12
|
|
Sildenafil + L-NMMA + Bradykinin
COMPLETED
|
12
|
|
Sildenafil + L-NMMA + Bradykinin
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
All Participants
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.
|
|---|---|
|
L-NMMA + Bradykinin
Physician Decision
|
1
|
Baseline Characteristics
Renin-Angiotensin Aldosterone System and Fibrinolysis Interaction in Humans-Specific Aim 3
Baseline characteristics by cohort
| Measure |
All Participants
n=24 Participants
Subjects characteristics for all 24 participants
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
31.71 years
STANDARD_DEVIATION 6.51 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: During and after each study drug administrationPopulation: 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.
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.
Outcome measures
| Measure |
Control
n=24 Participants
Subjects received bradykinin at 50, 100 and 200ng/min
|
L-NMMA + Control
n=23 Participants
After the intial bradykinin infusion subjects then received a continuous infusion of L-NMMA plus bradykinin at 50, 100 and 200ng/min
|
Isosorbide + L-NMMA + Control
n=11 Participants
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.
|
Sildenafil + L-NMMA + Control
n=12 Participants
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.
|
|---|---|---|---|---|
|
Net Tissue-type Plasminogen Activator (t-PA) Release
Net t-PA release (bradykinin 0ng/min)
|
0.24 ng/min/100ml
Standard Error 0.39
|
0.59 ng/min/100ml
Standard Error 0.23
|
-0.38 ng/min/100ml
Standard Error 0.51
|
0.29 ng/min/100ml
Standard Error 0.67
|
|
Net Tissue-type Plasminogen Activator (t-PA) Release
Net t-PA release (bradykinin 50ng/min)
|
1.02 ng/min/100ml
Standard Error 1.06
|
3.65 ng/min/100ml
Standard Error 0.79
|
3.14 ng/min/100ml
Standard Error 1.13
|
2.46 ng/min/100ml
Standard Error 2.07
|
|
Net Tissue-type Plasminogen Activator (t-PA) Release
Net t-PA release (bradykinin 100ng/min)
|
11.81 ng/min/100ml
Standard Error 2.12
|
22.10 ng/min/100ml
Standard Error 5.51
|
15.90 ng/min/100ml
Standard Error 3.13
|
18.48 ng/min/100ml
Standard Error 9.11
|
|
Net Tissue-type Plasminogen Activator (t-PA) Release
Net t-PA release (bradykinin 200ng/min)
|
30.03 ng/min/100ml
Standard Error 4.24
|
39.90 ng/min/100ml
Standard Error 6.98
|
45.32 ng/min/100ml
Standard Error 9.45
|
37.39 ng/min/100ml
Standard Error 11.79
|
SECONDARY outcome
Timeframe: During and after each study drug administrationForearm blood flow was measured by strain gauge plethysmography
Outcome measures
| Measure |
Control
n=24 Participants
Subjects received bradykinin at 50, 100 and 200ng/min
|
L-NMMA + Control
n=23 Participants
After the intial bradykinin infusion subjects then received a continuous infusion of L-NMMA plus bradykinin at 50, 100 and 200ng/min
|
Isosorbide + L-NMMA + Control
n=11 Participants
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.
|
Sildenafil + L-NMMA + Control
n=12 Participants
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.
|
|---|---|---|---|---|
|
Forearm Blood Flow (FBF)
FBF (bradykinin 200 ng/min)
|
17.74 ml/min/100ml
Standard Error 1.43
|
11.21 ml/min/100ml
Standard Error 1.12
|
9.91 ml/min/100ml
Standard Error 1.72
|
12.92 ml/min/100ml
Standard Error 1.30
|
|
Forearm Blood Flow (FBF)
FBF (bradykinin 0 ng/min)
|
4.03 ml/min/100ml
Standard Error 0.25
|
2.36 ml/min/100ml
Standard Error 0.18
|
2.18 ml/min/100ml
Standard Error 0.33
|
2.80 ml/min/100ml
Standard Error 0.37
|
|
Forearm Blood Flow (FBF)
FBF (bradykinin 50ng/min)
|
7.02 ml/min/100ml
Standard Error 0.57
|
5.16 ml/min/100ml
Standard Error 0.37
|
4.73 ml/min/100ml
Standard Error 0.70
|
5.87 ml/min/100ml
Standard Error 0.79
|
|
Forearm Blood Flow (FBF)
FBF (bradykinin 100ng/min)
|
13.17 ml/min/100ml
Standard Error 1.04
|
8.67 ml/min/100ml
Standard Error 0.81
|
6.83 ml/min/100ml
Standard Error 1.13
|
9.13 ml/min/100ml
Standard Error 0.76
|
OTHER_PRE_SPECIFIED outcome
Timeframe: At baseline and after maximum dose of bradykininIndividual 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.
Outcome measures
| Measure |
Control
n=24 Participants
Subjects received bradykinin at 50, 100 and 200ng/min
|
L-NMMA + Control
n=23 Participants
After the intial bradykinin infusion subjects then received a continuous infusion of L-NMMA plus bradykinin at 50, 100 and 200ng/min
|
Isosorbide + L-NMMA + Control
n=11 Participants
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.
|
Sildenafil + L-NMMA + Control
n=12 Participants
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.
|
|---|---|---|---|---|
|
Net Glucose Uptake
Net glucose uptake (bradykinin 0 ng/min)
|
-79.95 microgram/min/100ml
Standard Error 22.894
|
-74.36 microgram/min/100ml
Standard Error 7.125
|
-71.4 microgram/min/100ml
Standard Error 27.74
|
-67.3 microgram/min/100ml
Standard Error 13.17
|
|
Net Glucose Uptake
Net glucose uptake (bradykinin 200 ng/min)
|
-319.85 microgram/min/100ml
Standard Error 97.109
|
-142.86 microgram/min/100ml
Standard Error 49.935
|
-163.233 microgram/min/100ml
Standard Error 36.504
|
-125.32 microgram/min/100ml
Standard Error 45.705
|
Adverse Events
All Participants
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
All Participants
n=24 participants at risk
Subjects characteristics for all 24 participants
|
|---|---|
|
Nervous system disorders
Headache
|
8.3%
2/24 • Number of events 2
|
|
Nervous system disorders
fainted
|
4.2%
1/24 • Number of events 1
|
|
Vascular disorders
unexpected drug response
|
4.2%
1/24 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place