Pulmonary HypertensionEarly Phase 1NCT01950585
Hydroxyurea in Pulmonary Arterial Hypertension
A Early Phase 1 study testing Hydroxyurea in people with Pulmonary Hypertension, run by National Heart, Lung, and Blood Institute (NHLBI).
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 110 years
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- Hydroxyurea
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 6 Sep 2013to 23 Oct 2014
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 110 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age greater than or equal to 18 years old
- Patients with idiopathic or familial PAH with WHO II-III performance status
- On PAH medications that have not changed and are stable for the past two months
- Seronegative for HIV antibody, hepatitis B antigen, and hepatitis C antibody.
Who cannot join
- Thrombocytopenia with platelets less than 100,000/mm3, anemia with hemoglobin less than 10.5g/dL or neutropenia with ANC less than 1500/mm3
- Creatinine > 2.0mg/dL
- Hepatic insufficiency (transaminase levels >4 fold the upper limit of normal or bilirubin >2 fold the upper limit of normal)
- Severe arterial hypertension (systolic blood pressure >200mmHg or diastolic >120mmHg)
- Female subjects who are nursing or pregnant or are unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential
- Participation in any other investigative treatment studies at the time of enrollment
Show all 14Show fewer
- Unable to understand the investigational nature of the study or give informed consent (i.e. decisionally impaired)<TAB>
- Evidence of major bleeding or active infection
- Known allergy to the study drug or drugs similar to the study drug
- Subjects with known liver cirrhosis or chronic active hepatitis.
- HIV positivity
- Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient s ability to tolerate protocol therapy, or that death within 30 days is likely
- Presence of 9;22 BCR/ABL translocation as detected by conventional bone marrow cytogenetics or PCR for BCR/ABL transcript, or presence of JAK2 V617F mutation in bone marrow or peripheral blood cells.
- On beta-blocker therapy requiring dose adjustment.
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Pulmonary Hypertension
- Being tested
- Hydroxyurea
- Keywords
- Hydroxyurea, Pulmonary Hypertension, Idiopathic Pulmonary Arterial Hypertension, Familial Pulmonary Arterial Hypertension, CD34 + Cells
- Medical subject headings
- Hypertension, Pulmonary, Familial Primary Pulmonary Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxyureaDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
The change in concentration of CD34+ circulating progenitors from baseline to 6 months (24 weeks (+/- 7 days)) on hydroxyurea.
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2013 (estimated)
- Study start6 Sep 2013
- Primary completion23 Oct 2014
- Study completion23 Oct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- The Cleveland Clinic
- Responsible party
- Sponsor
- Investigators
- Moonjung Jung, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01950585
- Sponsor's protocol ID
- 130203
- Other IDs
- 13-H-0203
- Status last verified
- 23 Oct 2014
- First submitted
- 21 Sep 2013
- Last updated
- 16 Dec 2019
- Results posted
- No
Publications
Masri FA, Xu W, Comhair SA, Asosingh K, Koo M, Vasanji A, Drazba J, Anand-Apte B, Erzurum SC. Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L548-54. doi: 10.1152/ajplung.00428.2006. Epub 2007 May 25.
PubMed 17526595Farha S, Asosingh K, Xu W, Sharp J, George D, Comhair S, Park M, Tang WH, Loyd JE, Theil K, Tubbs R, Hsi E, Lichtin A, Erzurum SC. Hypoxia-inducible factors in human pulmonary arterial hypertension: a link to the intrinsic myeloid abnormalities. Blood. 2011 Mar 31;117(13):3485-93. doi: 10.1182/blood-2010-09-306357. Epub 2011 Jan 21.
PubMed 21258008Asosingh K, Farha S, Lichtin A, Graham B, George D, Aldred M, Hazen SL, Loyd J, Tuder R, Erzurum SC. Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension. Blood. 2012 Aug 9;120(6):1218-27. doi: 10.1182/blood-2012-03-419275. Epub 2012 Jun 28.
PubMed 22745307
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxyurea in Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT01950585
- Acronym / sponsor ID
- 130203
- Conditions
- Pulmonary Hypertension
- Keywords
- Hydroxyurea, Pulmonary Hypertension, Idiopathic Pulmonary Arterial Hypertension, Familial Pulmonary Arterial Hypertension, CD34 + Cells
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Collaborators
- The Cleveland Clinic
- Study start
- 6 Sep 2013
- Primary completion
- 23 Oct 2014 (actual)
- Study completion
- 23 Oct 2014 (actual)
- First posted
- 25 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 110 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age greater than or equal to 18 years old
- Patients with idiopathic or familial PAH with WHO II-III performance status
- On PAH medications that have not changed and are stable for the past two months
- Seronegative for HIV antibody, hepatitis B antigen, and hepatitis C antibody.
Key exclusion criteria (14 listed)
- Thrombocytopenia with platelets less than 100,000/mm3, anemia with hemoglobin less than 10.5g/dL or neutropenia with ANC less than 1500/mm3
- Creatinine > 2.0mg/dL
- Hepatic insufficiency (transaminase levels >4 fold the upper limit of normal or bilirubin >2 fold the upper limit of normal)
- Severe arterial hypertension (systolic blood pressure >200mmHg or diastolic >120mmHg)
- Female subjects who are nursing or pregnant or are unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxyurea | Drug | – |
Primary outcome
The change in concentration of CD34+ circulating progenitors from baseline to 6 months (24 weeks (+/- 7 days)) on hydroxyurea.
Time frame: ongoing
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2019.
- Background: PubMed 17526595Masri FA, Xu W, Comhair SA, Asosingh K, Koo M, Vasanji A, Drazba J, Anand-Apte B, Erzurum SC. Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L548-54. doi: 10.1152/ajplung.00428.2006. Epub 2007 May 25.
- Background: PubMed 21258008Farha S, Asosingh K, Xu W, Sharp J, George D, Comhair S, Park M, Tang WH, Loyd JE, Theil K, Tubbs R, Hsi E, Lichtin A, Erzurum SC. Hypoxia-inducible factors in human pulmonary arterial hypertension: a link to the intrinsic myeloid abnormalities. Blood. 2011 Mar 31;117(13):3485-93. doi: 10.1182/blood-2010-09-306357. Epub 2011 Jan 21.
- Background: PubMed 22745307Asosingh K, Farha S, Lichtin A, Graham B, George D, Aldred M, Hazen SL, Loyd J, Tuder R, Erzurum SC. Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension. Blood. 2012 Aug 9;120(6):1218-27. doi: 10.1182/blood-2012-03-419275. Epub 2012 Jun 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Moonjung Jung, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Hydroxyurea in people with Pulmonary Hypertension, run by National Heart, Lung, and Blood Institute (NHLBI).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 16 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The change in concentration of CD34+ circulating progenitors from baseline to 6 months (24 weeks (+/- 7 days)) on hydroxyurea. (time frame: ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01950585, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2019.