Ignite Creation Date:
2024-05-06 @ 2:02 AM
Last Modification Date:
2024-10-26 @ 11:12 AM
Study NCT ID:
NCT01950585
Status:
WITHDRAWN
Last Update Posted:
2019-12-16
First Post:
2013-09-21
Brief Title:
Hydroxyurea in Pulmonary Arterial Hypertension
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Hydroxyurea in Pulmonary Arterial Hypertension
Status:
WITHDRAWN
Status Verified Date:
2014-10-23
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Pulmonary arterial hypertension PAH is a serious and eventually fatal disease damaging the lungs and the heart It results from narrowing and eventual blockage of small blood vessels in the lung due to abnormal proliferation of cells in the blood vessel arterial Patients with PAH suffer from fatigue shortness of breath low oxygen levels blood clots and heart failure No therapies reverse the disease process in the lung arteries however there are three approved drugs that can temporarily dilate the vessels and improve symptoms However all three drugs have significant side effects and toxicities they do not work effectively in many patients survival remains on average only 2 to 3 years once symptoms begin and none of these drugs prevent the underlying disease process in the small arteries of the lung
PAH is known to develop in patients with a pre-existing class of bone marrow diseases called myeloproliferative disorders MPDs We and others have recently shown that patients with PAH have bone marrow changes similar to those seen in patients with MPDs even without other signs and symptoms of those bone marrow diseases such as anemia or high platelet and white blood cell counts Compared to healthy volunteers patients with PAH have a higher frequency of immature stem and progenitor cells able to produce blood cells and vascular wall cells in their bone marrow They also have higher circulating numbers of these cells in the blood and increased localization of these cells in the lung blood vessels When immature bone marrow cells from PAH patients and normal volunteers were infused into mice the mice receiving PAH marrow cells developed similar lung and heart problems to PAH patients suggesting that the bone marrow problem is a primary cause of the lung problems and that the increased numbers of immature bone marrow cells in the bone marrow and blood of PAH patients causes the lung blood vessel disease
The drug hydroxyurea is used to inhibit the abnormally high level of bone marrow cell proliferation in patients with MPDs It has been shown to reduce the numbers of circulating immature bone marrow cells in patients with MPDs Hydroxyurea has been available for almost fifty years and has been used to treat patients with MPDs sickle cell anemia and congenital heart disease for very prolonged periods of time up to twenty or more years in individual patients It has an excellent long-term safety profile and few side effects and is generally well tolerated It does not appear to result in an increased rate of leukemia even with many years of treatment
In the current protocol we hypothesize that treating patients with PAH with hydroxyurea will decrease the level of circulating immature bone marrow cells and interrupt the abnormal narrowing and occlusion of lung arteries We will treat patients with moderately severe primary no known underlying cause PAH with 6 months of hydroxyurea carefully monitoring side effects and adjusting dosage as necessary and measure the effect on circulating immature cells lung blood vessel pressures other blood markers of active PAH and exercise tolerance
PAH is known to develop in patients with a pre-existing class of bone marrow diseases called myeloproliferative disorders MPDs We and others have recently shown that patients with PAH have bone marrow changes similar to those seen in patients with MPDs even without other signs and symptoms of those bone marrow diseases such as anemia or high platelet and white blood cell counts Compared to healthy volunteers patients with PAH have a higher frequency of immature stem and progenitor cells able to produce blood cells and vascular wall cells in their bone marrow They also have higher circulating numbers of these cells in the blood and increased localization of these cells in the lung blood vessels When immature bone marrow cells from PAH patients and normal volunteers were infused into mice the mice receiving PAH marrow cells developed similar lung and heart problems to PAH patients suggesting that the bone marrow problem is a primary cause of the lung problems and that the increased numbers of immature bone marrow cells in the bone marrow and blood of PAH patients causes the lung blood vessel disease
The drug hydroxyurea is used to inhibit the abnormally high level of bone marrow cell proliferation in patients with MPDs It has been shown to reduce the numbers of circulating immature bone marrow cells in patients with MPDs Hydroxyurea has been available for almost fifty years and has been used to treat patients with MPDs sickle cell anemia and congenital heart disease for very prolonged periods of time up to twenty or more years in individual patients It has an excellent long-term safety profile and few side effects and is generally well tolerated It does not appear to result in an increased rate of leukemia even with many years of treatment
In the current protocol we hypothesize that treating patients with PAH with hydroxyurea will decrease the level of circulating immature bone marrow cells and interrupt the abnormal narrowing and occlusion of lung arteries We will treat patients with moderately severe primary no known underlying cause PAH with 6 months of hydroxyurea carefully monitoring side effects and adjusting dosage as necessary and measure the effect on circulating immature cells lung blood vessel pressures other blood markers of active PAH and exercise tolerance
Detailed Description:
Pulmonary arterial hypertension PAH is a serious and eventually fatal disease damaging the lungs and the heart It results from narrowing and eventual blockage of small blood vessels in the lung due to abnormal proliferation of cells in the blood vessel arterial Patients with PAH suffer from fatigue shortness of breath low oxygen levels blood clots and heart failure No therapies reverse the disease process in the lung arteries however there are three approved drugs that can temporarily dilate the vessels and improve symptoms However all three drugs have significant side effects and toxicities they do not work effectively in many patients survival remains on average only 2 to 3 years once symptoms begin and none of these drugs prevent the underlying disease process in the small arteries of the lung
PAH is known to develop in patients with a pre-existing class of bone marrow diseases called myeloproliferative disorders MPDs We and others have recently shown that patients with PAH have bone marrow changes similar to those seen in patients with MPDs even without other signs and symptoms of those bone marrow diseases such as anemia or high platelet and white blood cell counts Compared to healthy volunteers patients with PAH have a higher frequency of immature stem and progenitor cells able to produce blood cells and vascular wall cells in their bone marrow They also have higher circulating numbers of these cells in the blood and increased localization of these cells in the lung blood vessels When immature bone marrow cells from PAH patients and normal volunteers were infused into mice the mice receiving PAH marrow cells developed similar lung and heart problems to PAH patients suggesting that the bone marrow problem is a primary cause of the lung problems and that the increased numbers of immature bone marrow cells in the bone marrow and blood of PAH patients causes the lung blood vessel disease
The drug hydroxyurea is used to inhibit the abnormally high level of bone marrow cell proliferation in patients with MPDs It has been shown to reduce the numbers of circulating immature bone marrow cells in patients with MPDs Hydroxyurea has been available for almost fifty years and has been used to treat patients with MPDs sickle cell anemia and congenital heart disease for very prolonged periods of time up to twenty or more years in individual patients It has an excellent long-term safety profile and few side effects and is generally well tolerated It does not appear to result in an increased rate of leukemia even with many years of treatment
In the current protocol we hypothesize that treating patients with PAH with hydroxyurea will decrease the level of circulating immature bone marrow cells and interrupt the abnormal narrowing and occlusion of lung arteries We will treat patients with moderately severe primary no known underlying cause PAH with 6 months of hydroxyurea carefully monitoring side effects and adjusting dosage as necessary and measure the effect on circulating immature cells lung blood vessel pressures other blood markers of active PAH and exercise tolerance
PAH is known to develop in patients with a pre-existing class of bone marrow diseases called myeloproliferative disorders MPDs We and others have recently shown that patients with PAH have bone marrow changes similar to those seen in patients with MPDs even without other signs and symptoms of those bone marrow diseases such as anemia or high platelet and white blood cell counts Compared to healthy volunteers patients with PAH have a higher frequency of immature stem and progenitor cells able to produce blood cells and vascular wall cells in their bone marrow They also have higher circulating numbers of these cells in the blood and increased localization of these cells in the lung blood vessels When immature bone marrow cells from PAH patients and normal volunteers were infused into mice the mice receiving PAH marrow cells developed similar lung and heart problems to PAH patients suggesting that the bone marrow problem is a primary cause of the lung problems and that the increased numbers of immature bone marrow cells in the bone marrow and blood of PAH patients causes the lung blood vessel disease
The drug hydroxyurea is used to inhibit the abnormally high level of bone marrow cell proliferation in patients with MPDs It has been shown to reduce the numbers of circulating immature bone marrow cells in patients with MPDs Hydroxyurea has been available for almost fifty years and has been used to treat patients with MPDs sickle cell anemia and congenital heart disease for very prolonged periods of time up to twenty or more years in individual patients It has an excellent long-term safety profile and few side effects and is generally well tolerated It does not appear to result in an increased rate of leukemia even with many years of treatment
In the current protocol we hypothesize that treating patients with PAH with hydroxyurea will decrease the level of circulating immature bone marrow cells and interrupt the abnormal narrowing and occlusion of lung arteries We will treat patients with moderately severe primary no known underlying cause PAH with 6 months of hydroxyurea carefully monitoring side effects and adjusting dosage as necessary and measure the effect on circulating immature cells lung blood vessel pressures other blood markers of active PAH and exercise tolerance
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 13-H-0203 | None | None | None |