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| ID | Type | Description | Link |
|---|---|---|---|
| P01HL056693 | U.S. NIH Grant/Contract | View source |
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1. enrollment slower than anticipated; 2. FDA approval of droxidopa so no longer need to treat patients on research basis; 3. personnel who were primarily responsible for the study are no longer at Vanderbilt.
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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The purpose of this study is to try different medications in patients with low blood pressure and other problems with their involuntary (autonomic) nervous system. The pharmacological trials in this study will perhaps lead to more effective treatment. The protocol includes single dose trials, dose-selection trials, 5-day trials and chronic (approximately 2 months) trials, although only dose-selection trials were consistently performed and have results presented.
We see many patients at the Autonomic Dysfunction Center who can be given a fairly definitive diagnosis, e.g., Orthostatic Intolerance, Pure Autonomic Failure, Multiple System Atrophy, and Baroreflex Failure. However, some patients present with a unique constellation of symptoms of autonomic dysfunction so that they do not fit into a diagnostic category. We hypothesize that a genetic cause exists in some of these patients. We further propose that our comprehensive evaluation of these patients will provide us with information on the pathophysiology of their condition and assist us in optimizing their treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Droxidopa | Experimental | Patients with known or suspected Dopamine beta-Hydroxylase Deficiency were administered Droxidopa doses of 25 mg, 50 mg, 100 mg, 200 mg, 250 mg or 300 mg up to three times daily. Supine and upright blood pressures were subsequently measured 60 to 240 minutes post-dose. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Droxidopa Oral Product | Drug | Droxidopa administered in increasing dosages up to 300 mg |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Systolic Blood Pressure With Standing | The difference between upright and supine systolic blood pressures (dSBP; upright - supine) was calculated for each patient at 60-240 minutes after each dose of droxidopa. For each post-dose timepoint and study day, the average of up to three blood pressure readings per droxidopa dose was calculated. Dosing is individualized for each patient based upon how well the drug is tolerated and the degree of improvement in orthostatic vital signs and symptoms following drug administration. The dosages administered, as well as the number of timepoints and days, therefore, varied between patients. | Up to 240 minutes post dose on Study Days 1, 2, 3 and 4. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Robertson, MD | Vanderbilt University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University | Nashville | Tennessee | 37232 | United States |
Although all 8 patients received droxidopa while in the study, data is not included for 2 patients who had previously been treated with this medication.
Eight patients with known or suspected dopamine beta-hydroxylase (DBH) deficiency were invited or referred for enrollment in this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Patients With Dopamine Beta-Hydroxylase Deficiency | Patients with known or suspected dopamine beta-hydroxylase deficiency were treated with droxidopa up to 300 mg three time daily. Supine and upright blood pressures were subsequently measured and the length of time the patients were able to stand was ascertained. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Patients With Dopamine Beta-hydroxylase Deficiency | Patients with known or suspected dopamine beta-hydroxylase deficiency were treated with droxidopa up to 300 mg three time daily. Supine and upright blood pressures were subsequently measured and the length of time the patients were able to stand was ascertained. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 6 patients with DBH deficiency who had not been treated with droxidopa prior to study enrollment |
| 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 With Standing | The difference between upright and supine systolic blood pressures (dSBP; upright - supine) was calculated for each patient at 60-240 minutes after each dose of droxidopa. For each post-dose timepoint and study day, the average of up to three blood pressure readings per droxidopa dose was calculated. Dosing is individualized for each patient based upon how well the drug is tolerated and the degree of improvement in orthostatic vital signs and symptoms following drug administration. The dosages administered, as well as the number of timepoints and days, therefore, varied between patients. | Data is missing for 2 participants who had previously been treated with Droxidopa. In addition, since dosing was individualized for each patient, only those participants with data available at the specified timepoint were analyzed. | Posted | Median | Inter-Quartile Range | millimeters of mercury | Up to 240 minutes post dose on Study Days 1, 2, 3 and 4. |
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Patients stood for upright blood pressure measurements at 60 - 240 minutes following each dose of droxidopa and were asked about adverse events during this time period. Additionally, since patients were inpatient during the study, they were able to report any adverse events throughout the study.
Adverse event information was self-reported by participants and collected for any untoward or unfavorable medical occurrence temporally associated with participation in the research, whether or not considered related to the participant's participation in the research. All-Cause Mortality was not collected with respect to which dose level the patient was currently taking. Orthostatic hypotension and orthostatic symptoms characteristic of DBH deficiency were not considered adverse event.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Droxidopa 25 mg | Patients with known or suspected Dopamine beta-Hydroxylase Deficiency were treated with up to 3 doses per day. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alfredo Gamboa MD | Vanderbilt University Medical Center | 6158751003 | alfredo.gamboa@vumc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 14, 2003 | Jan 13, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 21, 2019 | Dec 2, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D001342 | Autonomic Nervous System Diseases |
| D007024 | Hypotension, Orthostatic |
| C535600 | dopamine beta hydroxylase deficiency |
| D054971 | Orthostatic Intolerance |
| D004244 | Dizziness |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
| D054969 | Primary Dysautonomias |
| D007022 | Hypotension |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D015103 | Droxidopa |
| ID | Term |
|---|---|
| D009638 | Norepinephrine |
| D002395 | Catecholamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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Although the study was designed as a potential trial of multiple medications, plus placebo, in actuality it served as a means of safely determining the optimal dose of Droxidopa for our patients with Dopamine beta-Hydroxylase Deficiency to take at home. Before each dose of Droxidopa, blood pressure and heart rate were measured for 30 minutes. At 60 or 120 minutes after dosing, blood pressure was also measured after 5 minutes of lying down and 5 minutes of sitting or standing. These measurements were used to calculate the orthostatic change in systolic blood pressure, the primary outcome.
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| Mean |
| Standard Deviation |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Droxidopa 25 mg |
Participants received up to 3 doses of Droxidopa 25 mg on Study Day 1, 2, 3 or 4. Individual dosing was dependent on how well the drug was tolerated and the degree of improvement in orthostatic signs and symptoms. |
| OG001 | Droxidopa 50 mg | Participants received up to 3 doses of Droxidopa 50 mg on Study Day 1, 2, 3 or 4. Individual dosing was dependent on how well the drug was tolerated and the degree of improvement in orthostatic signs and symptoms. |
| OG002 | Droxidopa 100 mg | Participants received up to 3 doses of Droxidopa 100 mg on Study Day 1, 2, 3 or 4. Individual dosing was dependent on how well the drug was tolerated and the degree of improvement in orthostatic signs and symptoms. |
| OG003 | Droxidopa 200 mg | Participants received up to 3 doses of Droxidopa 200 mg on Study Day 1, 2, 3 or 4. Individual dosing was dependent on how well the drug was tolerated and the degree of improvement in orthostatic signs and symptoms. |
| OG004 | Droxidopa 250 mg | Participants received up to 3 doses of Droxidopa 250 mg on Study Day 1, 2, 3 or 4. Individual dosing was dependent on how well the drug was tolerated and the degree of improvement in orthostatic signs and symptoms. |
| OG005 | Droxidopa 300 mg | Participants received up to 3 doses of Droxidopa 300 mg on Study Day 1, 2, 3 or 4. Individual dosing was dependent on how well the drug was tolerated and the degree of improvement in orthostatic signs and symptoms. |
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| 0 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | Droxidopa 50 mg | Patients with known or suspected Dopamine beta-Hydroxylase Deficiency were treated with up to 3 doses per day. | 0 | 8 | 0 | 8 | 0 | 8 |
| EG002 | Droxidopa 100 mg | Patients with known or suspected Dopamine beta-Hydroxylase Deficiency were treated with up to 3 doses per day. | 0 | 8 | 0 | 8 | 0 | 8 |
| EG003 | Droxidopa 200 mg | Patients with known or suspected Dopamine beta-Hydroxylase Deficiency were treated with up to 3 doses per day. | 0 | 8 | 0 | 8 | 0 | 8 |
| EG004 | Droxidopa 250 mg | Patients with known or suspected Dopamine beta-Hydroxylase Deficiency were treated with up to 3 doses per day. | 0 | 8 | 0 | 8 | 0 | 8 |
| EG005 | Droxidopa 300 mg | Patients with known or suspected Dopamine beta-Hydroxylase Deficiency were treated with up to 3 doses per day. | 0 | 8 | 0 | 8 | 0 | 8 |
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| D002318 |
| Cardiovascular Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012678 | Sensation Disorders |
| D002396 |
| Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D012694 | Serine |
| D021542 | Amino Acids, Neutral |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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