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Intravenous Norepinephrine for Orthostatic Hypotension

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ClinicalTrials.gov Identifier: NCT01285908
Recruitment Status : Completed
First Posted : January 28, 2011
Results First Posted : March 26, 2014
Last Update Posted : October 10, 2014
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Orthostatic Hypertension
Intervention Drug: Intravenous Norepinephrine Infusion
Enrollment 6

Recruitment Details Subjects were recruited through a NIH/NINDS screening protocol for Primary Chronic Autonomic Failure. Six subjects were enrolled during June 2011 to January 2012. Inclusion criteria required a confirmed diagnosis of neurogenic orthostatic hypotension related to Parkinson disease or pure autonomic failure.
Pre-assignment Details Subjects underwent history and physical exam following consent. Subjects not meeting eligibility criteria were excluded prior to baseline testing. One subject was excluded prior to baseline testing due to recent stroke and one subject was terminated from the study during the testing phase due to examiner's inability to place an arterial line.
Arm/Group Title Baseline Saline, Then Norepinephrine Norepinephrine, Then Saline
Hide Arm/Group Description Orthostatic hypotension was measured while lying flat (0 degrees) and at varying tilt angles (20, 40, and 60 degrees). Baseline measures included the following: blood pressure (systolic and diastolic), mean arterial pressure, heart rate, cardiac stroke volume, cardiac output, total peripheral resistance, plasma levels of norepinephrine and dihydroxyphenylglycol. Orthostatic hypotension was measured while lying flat (0 degrees) and at varying tilt angles (20, 40, and 60 degrees) under two separate conditions, i.e., first following IV administration of saline followed by IV administration of norepinephrine. Measures included the following: blood pressure (systolic and diastolic), mean arterial pressure, heart rate, cardiac stroke volume, cardiac output, total peripheral resistance, plasma levels of norepinephrine and dihydroxyphenylglycol. Orthostatic hypotension was measured while lying flat (0 degrees) and at varying tilt angles (20, 40, and 60 degrees) under two separate conditions, i.e., first following IV administration of norepinephrine followed by IV administration of saline. Measures included the following: blood pressure (systolic and diastolic), mean arterial pressure, heart rate, cardiac stroke volume, cardiac output, total peripheral resistance, plasma levels of norepinephrine and dihydroxyphenylglycol.
Period Title: Baseline Measurement
Started 6 0 0
Completed 3 0 0
Not Completed 3 0 0
Reason Not Completed
unable to insert catheter             1             0             0
History of stroke, exclusion criteria             1             0             0
unable to tolerate procedure             1             0             0
Period Title: Treatment Crossover
Started 0 2 [1] 2
Completed 0 2 2
Not Completed 0 0 0
[1]
One subject in treatment crossover did not complete baseline testing as unable to complete tasks
Arm/Group Title All Study Participants
Hide Arm/Group Description The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or Pure Autonomic Failure.
Overall Number of Baseline Participants 5
Hide Baseline Analysis Population Description
Baseline characteristics are included for all subjects meeting eligibility criteria.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
<=18 years
0
   0.0%
Between 18 and 65 years
2
  40.0%
>=65 years
3
  60.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants
65  (4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Female
2
  40.0%
Male
3
  60.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 5 participants
5
1.Primary Outcome
Title Blood Pressure (Systolic)
Hide Description The extent to which norepinephrine infusion maintains blood pressure, by comparison with the changes in systolic pressure at varying tilt angles during baseline and saline infusion.
Time Frame 2 experimental days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was unable to tolerate tilting to 60 degrees following saline infusion and one subject was unable to tolerate tilting to 40 degrees following saline infusion; therefore the data for these subjects was not included in the saline condition.
Arm/Group Title Baseline Saline Norepinephrine
Hide Arm/Group Description:
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with baseline measurements of systolic blood pressure taken at varying tilt angles.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of blood pressure taken at varying tilt angles following a saline infusion.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of blood pressure taken at varying tilt angles following a norepinephrine infusion.
Overall Number of Participants Analyzed 3 2 4
Mean (Standard Deviation)
Unit of Measure: mm Hg
Tilt Angle 0 156  (15) 158  (16) 179  (14)
Tilt Angle 20 148  (11) 149  (9) 173  (10)
Tilt Angle 40 131  (48) 128  (4) 167  (11)
Tilt Angle 60 112  (3) 120  (3) 175  (15)
2.Primary Outcome
Title Blood Pressure (Diastolic)
Hide Description The extent to which norepinephrine infusion maintains blood pressure, by comparison with the changes in diastolic pressure at varying tilt angles during baseline and saline infusion.
Time Frame 2 experimental days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was unable to tolerate tilting to 60 degrees following saline infusion and one subject was unable to tolerate tilting to 40 degrees following saline infusion; therefore the data for these subjects was not included in the saline condition.
Arm/Group Title Baseline Saline Norepinephrine
Hide Arm/Group Description:
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure, with baseline measurements of diastolic blood pressure taken at varying tilt angles.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of blood pressure taken at varying tilt angles following a saline infusion.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of blood pressure taken at varying tilt angles following a norepinephrine infusion.
Overall Number of Participants Analyzed 3 2 4
Mean (Standard Deviation)
Unit of Measure: mm Hg
Tilt Angle 0 83  (7) 83  (2) 95  (6)
Tilt Angle 20 85  (6) 84  (3) 95  (4)
Tilt Angle 40 79  (4) 81  (4) 92  (5)
Tilt Angle 60 73  (3) 80  (4) 98  (7)
3.Primary Outcome
Title Blood Pressure (Mean)
Hide Description The extent to which norepinephrine infusion maintains average blood pressure, by comparison with the fractional changes in blood pressure at varying tilt angles during baseline and saline infusion.
Time Frame 2 experimental days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was unable to tolerate tilting to 60 degrees following saline infusion and one subject was unable to tolerate tilting to 40 degrees following saline infusion; therefore the data for these subjects was not included in the saline condition.
Arm/Group Title Baseline Saline Norepinephrine
Hide Arm/Group Description:
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure, with baseline measurements of average blood pressure taken at varying tilt angles.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of average blood pressure taken at varying tilt angles following a saline infusion.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of average blood pressure taken at varying tilt angles following a norepinephrine infusion.
Overall Number of Participants Analyzed 3 2 4
Mean (Standard Deviation)
Unit of Measure: mm Hg
Tilt Angle 0 107  (10) 108  (7) 123  (9)
Tilt Angle 20 106  (8) 106  (5) 121  (6)
Tilt Angle 40 96  (45) 97  (4) 116  (7)
Tilt Angle 60 86  (3) 93  (3) 124  (9)
4.Secondary Outcome
Title Heart Rate
Hide Description The extent to which norepinephrine infusion affects heart rate, by comparison of beat-to-beat heart rate at varying tilt angles during baseline and saline infusion.
Time Frame 2 experimental days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was unable to tolerate tilting to 60 degrees following saline infusion and one subject was unable to tolerate tilting to 40 degrees following saline infusion; therefore the data for these subjects was not included in the saline condition.
Arm/Group Title Baseline Saline Norepinephrine
Hide Arm/Group Description:
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with baseline measurements of heart rate taken at varying tilt angles.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of heart rate taken at varying tilt angles following a saline infusion.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of heart rate taken at varying tilt angles following a norepinephrine infusion.
Overall Number of Participants Analyzed 3 2 4
Mean (Standard Deviation)
Unit of Measure: bpm
Tilt Angle 0 62  (4) 55  (8) 58  (5)
Tilt Angle 20 57  (2) 56  (3) 60  (4)
Tilt Angle 40 55  (3) 58  (3) 59  (4)
Tilt Angle 60 65  (3) 63  (4) 63  (2)
5.Secondary Outcome
Title Cardiac Stroke Volume
Hide Description The extent to which norepinephrine infusion affects cardiac stroke volume, by comparison of cardiac stroke volume at varying tilt angles during baseline and saline infusion.
Time Frame 2 experimental days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was unable to tolerate tilting to 60 degrees following saline infusion and one subject was unable to tolerate tilting to 40 degrees following saline infusion; therefore the data for these subjects was not included in the saline condition.
Arm/Group Title Baseline Saline Norepinephrine
Hide Arm/Group Description:
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure, with baseline measurements of cardiac stroke volume taken at varying tilt angles.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of cardiac stroke volume taken at varying tilt angles following a saline infusion.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of cardiac stroke volume taken at varying tilt angles following a norepinephrine infusion.
Overall Number of Participants Analyzed 3 2 4
Mean (Standard Deviation)
Unit of Measure: mL
Tilt Angle 0 76  (15) 66  (20) 83  (13)
Tilt Angle 20 70  (15) 62  (20) 82  (13)
Tilt Angle 40 62  (13) 56  (18) 76  (11)
Tilt Angle 60 52  (5) 50  (14) 67  (12)
6.Secondary Outcome
Title Cardiac Output
Hide Description The extent to which norepinephrine infusion affects cardiac output, by comparison of cardiac output at varying tilt angles during baseline and saline infusion.
Time Frame 2 experimental days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was unable to tolerate tilting to 60 degrees following saline infusion and one subject was unable to tolerate tilting to 40 degrees following saline infusion; therefore the data for these subjects was not included in the saline condition.
Arm/Group Title Baseline Saline Norepinephrine
Hide Arm/Group Description:
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure, with baseline measurements of cardiac output taken at varying tilt angles.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of cardiac output taken at varying tilt angles following a saline infusion.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of cardiac output taken at varying tilt angles following a norepinephrine infusion.
Overall Number of Participants Analyzed 3 2 4
Mean (Standard Deviation)
Unit of Measure: L/min
Tilt Angle 0 4.6  (0.6) 3.8  (1.6) 4.9  (1.0)
Tilt Angle 20 3.9  (0.7) 3.5  (1.3) 5.1  (1.0)
Tilt Angle 40 3.4  (0.5) 3.3  (1.2) 4.6  (0.9)
Tilt Angle 60 3.4  (0.4) 3.2  (1.1) 4.2  (0.8)
7.Secondary Outcome
Title Total Peripheral Resistance
Hide Description The extent to which norepinephrine infusion affected total peripheral resistance, by comparison of total peripheral resistance at varying tilt angles during baseline and saline infusion.
Time Frame 2 experimental days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was unable to tolerate tilting to 60 degrees following saline infusion and one subject was unable to tolerate tilting to 40 degrees following saline infusion; therefore the data for these subjects was not included in the saline condition.
Arm/Group Title Baseline Saline Norepinephrine
Hide Arm/Group Description:
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure, with baseline measurements of total peripheral resistance taken at varying tilt angles.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of total peripheral resistance taken at varying tilt angles following a saline infusion.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of total peripheral resistance taken at varying tilt angles following a norepinephrine infusion.
Overall Number of Participants Analyzed 3 2 4
Mean (Standard Deviation)
Unit of Measure: mmHg/(min/L)
Tilt Angle 0 22.4  (1.6) 34  (16) 27  (6)
Tilt Angle 20 26.9  (3.1) 33  (14) 26  (7)
Tilt Angle 40 27.7  (3.5) 32  (13) 28  (7)
Tilt Angle 60 24.5  (2.8) 30  (9) 31  (6)
8.Secondary Outcome
Title Arterial Plasma Levels of Norepinephrine
Hide Description Plasma levels of norepinephrine are obtained from blood samples via IV catheter.
Time Frame 2 experimental days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was unable to tolerate tilting to 60 degrees following saline infusion and one subject was unable to tolerate tilting to 40 degrees following saline infusion; therefore the data for these subjects was not included in the saline condition.
Arm/Group Title Baseline Saline Norepinephrine
Hide Arm/Group Description:
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with baseline measurements of plasma levels of norepinephrine at varying tilt angles.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of plasma levels of norepinephrine taken at varying tilt angles following a saline infusion.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of plasma levels of norepinephrine taken at varying tilt angles following a norepinephrine infusion.
Overall Number of Participants Analyzed 3 2 4
Mean (Standard Deviation)
Unit of Measure: nmol/L
Tilt Angle 0 0.78  (0.29) 0.82  (0.33) 0.73  (0.22)
Tilt Angle 20 0.89  (0.34) 0.65  (0.22) 1.99  (0.67)
Tilt Angle 40 1.04  (0.4) 0.97  (0.39) 3.73  (0.94)
Tilt Angle 60 1.3  (0.48) 2.32  (0.02) 7.83  (1.4)
9.Secondary Outcome
Title Arterial Plasma Levels of Dihydroxyphenylglycol (DHPG)
Hide Description Plasma levels of dihydroxyphenylglycol are obtained from blood samples via IV catheter.
Time Frame 2 experimental days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was unable to tolerate tilting to 60 degrees following saline infusion and one subject was unable to tolerate tilting to 40 degrees following saline infusion; therefore the data for these subjects was not included in the saline condition.
Arm/Group Title Baseline Saline Norepinephrine
Hide Arm/Group Description:
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure, with baseline measurements of plasma levels of dihydroxyphenylglycol at varying tilt angles.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of plasma levels of dihydroxyphenylglycol taken at varying tilt angles following a saline infusion.
The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements of plasma levels of dihydroxyphenylglycol taken at varying tilt angles following a norepinephrine infusion.
Overall Number of Participants Analyzed 3 2 4
Mean (Standard Deviation)
Unit of Measure: nmol/L
Tilt Angle 0 3.42  (0.26) 4.01  (0.32) 4.07  (0.40)
Tilt Angle 20 3.44  (0.22) 3.97  (0.28) 4.05  (0.34)
Tilt Angle 40 3.82  (0.46) 4.18  (0.30) 4.12  (0.45)
Tilt Angle 60 4.39  (0.56) 5.00  (0.33) 4.47  (0.52)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Baseline Saline, Then Norepinephrine Norepinephrine, Then Saline
Hide Arm/Group Description The participants are patients with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with baseline measurements of BP at varying tilt angles. The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements taken at varying tilt angles under two separate conditions, i.e., following IV administration of saline, followed by IV administration of norepinephrine. The participants are subjects with neurogenic orthostatic hypotension associated with Parkinson disease or pure autonomic failure with measurements taken at varying tilt angles under two separate conditions, i.e., following IV administration of norepinephrine, followed by IV administration of saline.
All-Cause Mortality
Baseline Saline, Then Norepinephrine Norepinephrine, Then Saline
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Baseline Saline, Then Norepinephrine Norepinephrine, Then Saline
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/6 (0.00%)      0/2 (0.00%)      0/2 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Baseline Saline, Then Norepinephrine Norepinephrine, Then Saline
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/6 (16.67%)      0/2 (0.00%)      0/2 (0.00%)    
Skin and subcutaneous tissue disorders       
Eccymoses [1]  1/6 (16.67%)  1 0/2 (0.00%)  0 0/2 (0.00%)  0
[1]
Ecchymoses in the arms after failed attempts to place brachial and radial arterial catheters
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. David S. Goldstein
Organization: National Institute of Neurological Disorders & Stroke
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT01285908     History of Changes
Other Study ID Numbers: 110085
11-N-0085
First Submitted: January 25, 2011
First Posted: January 28, 2011
Results First Submitted: September 24, 2013
Results First Posted: March 26, 2014
Last Update Posted: October 10, 2014