Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| NIH 1RO1HL71172 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The amount of blood flowing to the different parts of the body is regulated by the autonomic (automatic) nerves and by local factors produced by the blood vessels. Nitric oxide (NO) is one of the most important of these metabolic factors. If the production of NO is slowed or stopped the amount of blood to the different parts of the body is decreased. There is increasing knowledge that NO mechanisms are impaired in a number of medical conditions. NO function is reduced in patients with risk factors for atherosclerosis (hardening of the arteries) such as hypercholesterolemia (patients with high cholesterol), or diabetes mellitus, and is also impaired in smokers. This NO "deficiency" is believed to contribute to the greater cardiovascular risk that marks these patient populations. This study is designed to examine if endothelial nitric oxide is an important control mechanism of blood pressure under normal conditions, and if impairment of nitric oxide contributes to hypertension.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Autonomic Failure Patients | Experimental | To compare the effects of NO inhibition during intact and transient pharmacological blockade of the autonomic nervous system in Patients with Autonomic Failure. |
|
| Controls and hypertensives | Experimental | To compare the effects of NO inhibition during intact and transient pharmacological blockade of the autonomic nervous system in normal volunteers and hypertensive subjects. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-NMMA | Drug | IV infusion of 125, 250 and 500 mcg/Kg/min for 15 minutes each dose. The main outcome is the maximal increase in blood pressure produced at the end of the infusions or a maximal systolic blood pressure of 160 mm Hg. It could be achieved after the first dose or the third. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Systolic Blood Pressure | L-NMMA (nitric oxide synthase inhibitor) was infused intravenously at different doses for 15 minutes each, after blocking the autonomic nervous system with trimethaphan. The change in systolic blood pressure at the end of the highest tolerated dose is the main outcome. Trimethaphan infused intravenously was used to produce transient blockade of the autonomic nervous system to allow for a full response to nitric oxide inhibition (in the absence of the baroreflex. | At the end of the highest tolerated dose of IV infusion of L-NMMA |
| Systolic Blood Pressure in Response to Systemic Nitric Oxide Inhibition | Systolic blood pressure at the highest tolerated dose of IV infusion of L-NMMA during autonomic nervous system blockade with trimethaphan. Trimethaphan, infused intravenously was used to produce transient blockade of the autonomic nervous system to allow for a full response to nitric oxide inhibition (in the absence of the baroreflex. | End of 15 minutes of infusion of L-NMMA at the highest tolerated dose |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Italo Biaggioni, M.D. | Vanderbilt University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Autonomic Dysfunction Center | Nashville | Tennessee | 37232 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18426998 | Derived | Gamboa A, Shibao C, Diedrich A, Paranjape SY, Farley G, Christman B, Raj SR, Robertson D, Biaggioni I. Excessive nitric oxide function and blood pressure regulation in patients with autonomic failure. Hypertension. 2008 Jun;51(6):1531-6. doi: 10.1161/HYPERTENSIONAHA.107.105171. Epub 2008 Apr 21. | |
| 17130304 | Derived |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Autonomic Failure Patients | The NO synthase inhibitor L-NMMA was infused intravenously at different doses (125, 250 and 500 mcg/kg/min) until a systolic blood pressure of 150 mm Hg was reached. |
| FG001 | Hypertensives and Controls | The NO synthase inhibitor L-NMMA was infused intravenously at different doses (250, 500 mcg/kg/min) for 15 minutes each dose after acute transient pharmacological blockade of the autonomic nervous system with trimethaphan (4 mg/min) or with the autonomic nervous system intact. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Autonomic Failure Patients | To compare the effects of NO inhibition during intact and transient pharmacological blockade of the autonomic nervous system. |
| BG001 | Hypertensives and Controls |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Systolic Blood Pressure | L-NMMA (nitric oxide synthase inhibitor) was infused intravenously at different doses for 15 minutes each, after blocking the autonomic nervous system with trimethaphan. The change in systolic blood pressure at the end of the highest tolerated dose is the main outcome. Trimethaphan infused intravenously was used to produce transient blockade of the autonomic nervous system to allow for a full response to nitric oxide inhibition (in the absence of the baroreflex. | Posted | Mean | Standard Error | mm Hg | At the end of the highest tolerated dose of IV infusion of L-NMMA |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Autonomic Failure Patients | The NO synthase inhibitor L-NMMA was infused intravenously at different doses (125, 250 and 500 mcg/kg/min) until a systolic blood pressure of 150 mm Hg was reached. |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Italo Biaggioni | Vanderbilt University | 615-343-6499 | italo.biaggioni@vanderbilt.edu |
Not provided
| ID | Term |
|---|---|
| D006973 | Hypertension |
| D054970 | Pure Autonomic Failure |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D019323 | omega-N-Methylarginine |
| D014294 | Trimethaphan |
| ID | Term |
|---|---|
| D001120 | Arginine |
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Trimethaphan | Drug | IV infusion for the duration of the study at 4-6 mg/min depending on autonomic blockade. This is only to produce transient pharmacological blockade of the autonomic nervous system in order to allow the full expression of the inhibition of nitric oxide synthase. There is no direct outcome associated with this intervention. |
|
| Gamboa A, Shibao C, Diedrich A, Choi L, Pohar B, Jordan J, Paranjape S, Farley G, Biaggioni I. Contribution of endothelial nitric oxide to blood pressure in humans. Hypertension. 2007 Jan;49(1):170-7. doi: 10.1161/01.HYP.0000252425.06216.26. Epub 2006 Nov 27. |
To compare the effects of NO inhibition during intact and transient pharmacological blockade of the autonomic nervous system
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
To compare the effects of NO inhibition during intact and transient pharmacological blockade of the autonomic nervous system |
|
|
| Primary | Systolic Blood Pressure in Response to Systemic Nitric Oxide Inhibition | Systolic blood pressure at the highest tolerated dose of IV infusion of L-NMMA during autonomic nervous system blockade with trimethaphan. Trimethaphan, infused intravenously was used to produce transient blockade of the autonomic nervous system to allow for a full response to nitric oxide inhibition (in the absence of the baroreflex. | Posted | Mean | Standard Deviation | mm Hg | End of 15 minutes of infusion of L-NMMA at the highest tolerated dose |
|
|
|
| 0 |
| 19 |
| 0 |
| 19 |
| EG001 | Hypertensives and Controls | The NO synthase inhibitor L-NMMA was infused intravenously at different doses (250, 500 mcg/kg/min) for 15 minutes each dose after acute transient pharmacological blockade of the autonomic nervous system with trimethaphan (4 mg/min) or with the autonomic nervous system intact. | 0 | 93 | 0 | 93 |
Not provided
Not provided
Not provided
| D009422 | Nervous System Diseases |
| D000599 |
| Amino Acids, Diamino |
| D000601 | Amino Acids, Essential |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |