Pulmonary HypertensionNCT00011648
Secondary Pulmonary Hypertension in Adults With Sickle Cell Anemia
An observational study of Pulmonary Hypertension and Sickle Cell Anemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites in United States.
Trial summary
The purpose of this study is to determine how often people with sickle cell anemia develop pulmonary hypertension a serious disease in which blood pressure in the artery to the lungs is elevated. Men and women 18 years of age and older with sickle cell anemia may be eligible for this study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Hypertension, Sickle Cell Anemia, Sickle Cell Disease
- How many people
- 986 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Feb 2008to not given
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Male and females African American subjects over 18 years of age. Exclusion of sickle cell disease (electrophoretic documentation of hemoglobin A is required)
Who may be able to join
- Male and females over 18 years of age.
- Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S-beta thallassemia genotype is required).
- Male and females African American subjects over 18 years of age.
- Exclusion of sickle cell disease (electrophoretic documentation of hemoglobin A is required).
Who cannot join
- Hb A-only phenotype and sickle cell trait.
- Decisionally impaired subjects.
- Pregnant or lactating women
- Diagnosis of sickle cell disease (electrophoretic documentation of SS, or SC, or SB thallassemia genotype is required.)
- Decisionally impaired subjects.
- Pregnant or lactating women
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Howard University Hospital
Washington D.C., District of Columbia, 20060
About this study
Official title: Determining the Prevalence and Prognosis of Secondary Pulmonary Hypertension in Adult Patients With Sickle Cell Anemia
The purpose of this study is to determine how often people with sickle cell anemia develop pulmonary hypertension a serious disease in which blood pressure in the artery to the lungs is elevated.
Men and women 18 years of age and older with sickle cell anemia may be eligible for this study. Participants will undergo an evaluation at Howard University s Comprehensive Sickle Cell Center in Washington, D.C. or at the National Institutes of Health in Bethesda, Maryland. It will include the following:
Read more
- medical history
- physical examination
- blood collection (no more than 50 ml., or about 1/3 cup) to confirm the diagnosis of sickle cell anemia, sickle cell trait or beta-thalassemia (Some blood will be stored for future research testing on sickle cell anemia.)
- echocardiogram (ultrasound test of the heart) to check the pumping action of the heart and the rate at which blood travels through the tricuspid valve.
Following this evaluation, a study nurse will contact participants twice a month for 2 months and then once every 3 months for the next 3 years for a telephone interview. The interview will include questions about general health and recent health-related events, such as hospitalizations or emergency room visits.
Read the detailed description
Sickle cell anemia is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% have sickle cell trait. Acute pain crisis, acute chest syndrome (ACS), and secondary pulmonary hypertension are common complications of sickle cell anemia. Mortality rates of sickle cell patients with pulmonary hypertension are significantly increased as compared to patients without pulmonary hypertension. Recent studies report up to 40% mortality at 22 months after detection of elevated pulmonary artery pressures in sickle cell patients. Furthermore, pulmonary hypertension is thought to occur in up to 30% of clinic patients with sickle cell anemia.
This study is designed to determine the prevalence and prognosis of secondary pulmonary hypertension in adult patients with sickle cell anemia, and to determine whether genetic polymorphisms in candidate genes contribute to its development or response to treatment.
- Keywords
- Echocardiogram, Morbidity, Mortality, Natural History, Sickle Cell Anemia, Secondary Pulmonary Hypertension
- Medical subject headings
- Hypertension, Pulmonary, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| non-SCD | 200 Men and Women without a diagnosis of sickle cell disease 18 years of age or older | |
| SCD | 1000 Men and Women with a diagnosis of sickle cell disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the prevalence and prognosis of secondary pulmonary hypertension in adult patients with sickle cell anemia.
predictive of any clinical outcome or response in sickle cell disease will provide preliminary evidence for further investigation
Measured: 10 years
Secondary outcomes (1)
To determine whether genetic polymorphisms in candidate genes contribute to its development or response to treatment.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2001 (estimated)
- Study start19 Feb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 986 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Swee Lay Thein, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00011648
- Sponsor's protocol ID
- 010088
- Other IDs
- 01-H-0088
- Status last verified
- 4 Jun 2026
- First submitted
- 24 Feb 2001
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Li H, Gao S, Wang X, Asomaning N, Conrey A, Kruah B, Joo J, Wu CO, Sachdev V, Thein SL. Transthyretin V122I variant and protein affect cardiac severity and mortality in sickle cell disease. Blood Adv. 2026 Jun 9;10(11):4000-4008. doi: 10.1182/bloodadvances.2026019698.
PubMed 41921073Parrow NL, Doherty JM, Conrey A, Thein SL, Fleming RE. Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease. Adv Hematol. 2024 Dec 3;2024:9872440. doi: 10.1155/ah/9872440. eCollection 2024.
PubMed 39659429van Vuren AJ, Minniti CP, Mendelsohn L, Baird JH, Kato GJ, van Beers EJ. Lactate dehydrogenase to carboxyhemoglobin ratio as a biomarker of heme release to heme processing is associated with higher tricuspid regurgitant jet velocity and early death in sickle cell disease. Am J Hematol. 2021 Sep 1;96(9):E315-E318. doi: 10.1002/ajh.26243. Epub 2021 Jun 10. No abstract available.
PubMed 34000072Sachdev V, Tian X, Gu Y, Nichols J, Sidenko S, Li W, Beri A, Layne WA, Allen D, Wu CO, Thein SL. A phenotypic risk score for predicting mortality in sickle cell disease. Br J Haematol. 2021 Mar;192(5):932-941. doi: 10.1111/bjh.17342. Epub 2021 Jan 28.
PubMed 33506990Nguyen KL, Tian X, Alam S, Mehari A, Leung SW, Seamon C, Allen D, Minniti CP, Sachdev V, Arai AE, Kato GJ. Elevated transpulmonary gradient and cardiac magnetic resonance-derived right ventricular remodeling predict poor outcomes in sickle cell disease. Haematologica. 2016 Feb;101(2):e40-3. doi: 10.3324/haematol.2015.125229. Epub 2015 Nov 20. No abstract available.
PubMed 26589907Fitzhugh CD, Hsieh MM, Allen D, Coles WA, Seamon C, Ring M, Zhao X, Minniti CP, Rodgers GP, Schechter AN, Tisdale JF, Taylor JG 6th. Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia. PLoS One. 2015 Nov 17;10(11):e0141706. doi: 10.1371/journal.pone.0141706. eCollection 2015.
PubMed 26576059Wallen GR, Minniti CP, Krumlauf M, Eckes E, Allen D, Oguhebe A, Seamon C, Darbari DS, Hildesheim M, Yang L, Schulden JD, Kato GJ, Taylor JG 6th. Sleep disturbance, depression and pain in adults with sickle cell disease. BMC Psychiatry. 2014 Jul 21;14:207. doi: 10.1186/1471-244X-14-207.
PubMed 25047658Darbari DS, Wang Z, Kwak M, Hildesheim M, Nichols J, Allen D, Seamon C, Peters-Lawrence M, Conrey A, Hall MK, Kato GJ, Taylor JG 6th. Severe painful vaso-occlusive crises and mortality in a contemporary adult sickle cell anemia cohort study. PLoS One. 2013 Nov 5;8(11):e79923. doi: 10.1371/journal.pone.0079923. eCollection 2013.
PubMed 24224021Nekhai S, Xu M, Foster A, Kasvosve I, Diaz S, Machado RF, Castro OL, Kato GJ, Taylor JG 6th, Gordeuk VR. Reduced sensitivity of the ferroportin Q248H mutant to physiological concentrations of hepcidin. Haematologica. 2013 Mar;98(3):455-63. doi: 10.3324/haematol.2012.066530. Epub 2012 Oct 12.
PubMed 23065513Minniti CP, Taylor JG 6th, Hildesheim M, O'Neal P, Wilson J, Castro O, Gordeuk VR, Kato GJ. Laboratory and echocardiography markers in sickle cell patients with leg ulcers. Am J Hematol. 2011 Aug;86(8):705-8. doi: 10.1002/ajh.22065. Epub 2011 May 31.
PubMed 21630312Sundaram N, Tailor A, Mendelsohn L, Wansapura J, Wang X, Higashimoto T, Pauciulo MW, Gottliebson W, Kalra VK, Nichols WC, Kato GJ, Malik P. High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension. Blood. 2010 Jul 8;116(1):109-12. doi: 10.1182/blood-2009-09-244830. Epub 2010 Mar 24.
PubMed 20335221Kato GJ, Wang Z, Machado RF, Blackwelder WC, Taylor JG 6th, Hazen SL. Endogenous nitric oxide synthase inhibitors in sickle cell disease: abnormal levels and correlations with pulmonary hypertension, desaturation, haemolysis, organ dysfunction and death. Br J Haematol. 2009 May;145(4):506-13. doi: 10.1111/j.1365-2141.2009.07658.x. Epub 2008 Mar 17.
PubMed 19344390
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determining the Prevalence and Prognosis of Secondary Pulmonary Hypertension in Adult Patients With Sickle Cell Anemia
- ClinicalTrials.gov ID
- NCT00011648
- Acronym / sponsor ID
- 010088
- Keywords
- Echocardiogram, Morbidity, Mortality, Natural History, Sickle Cell Anemia, Secondary Pulmonary Hypertension
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 986 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 19 Feb 2008 (actual)
- First posted
- 26 Feb 2001 (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.
The purpose of this study is to determine how often people with sickle cell anemia develop pulmonary hypertension a serious disease in which blood pressure in the artery to the lungs is elevated.
Men and women 18 years of age and older with sickle cell anemia may be eligible for this study. Participants will undergo an evaluation at Howard University s Comprehensive Sickle Cell Center in Washington, D.C. or at the National Institutes of Health in Bethesda, Maryland. It will include the following:
- medical history
- physical examination
- blood collection (no more than 50 ml., or about 1/3 cup) to confirm the diagnosis of sickle cell anemia, sickle cell trait or beta-thalassemia (Some blood will be stored for future research testing on sickle cell anemia.)
- echocardiogram (ultrasound test of the heart) to check the pumping action of the heart and the rate at which blood travels through the tricuspid valve.
Following this evaluation, a study nurse will contact participants twice a month for 2 months and then once every 3 months for the next 3 years for a telephone interview. The interview will include questions about general health and recent health-related events, such as hospitalizations or emergency room visits.
Detailed description
Sickle cell anemia is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% have sickle cell trait. Acute pain crisis, acute chest syndrome (ACS), and secondary pulmonary hypertension are common complications of sickle cell anemia. Mortality rates of sickle cell patients with pulmonary hypertension are significantly increased as compared to patients without pulmonary hypertension. Recent studies report up to 40% mortality at 22 months after detection of elevated pulmonary artery pressures in sickle cell patients. Furthermore, pulmonary hypertension is thought to occur in up to 30% of clinic patients with sickle cell anemia.
This study is designed to determine the prevalence and prognosis of secondary pulmonary hypertension in adult patients with sickle cell anemia, and to determine whether genetic polymorphisms in candidate genes contribute to its development or response to treatment.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| non-SCD | – | –200 Men and Women without a diagnosis of sickle cell disease 18 years of age or older |
| SCD | – | –1000 Men and Women with a diagnosis of sickle cell disease |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Male and females African American subjects over 18 years of age. Exclusion of sickle cell disease (electrophoretic documentation of hemoglobin A is required)
Key inclusion criteria (4 listed)
- Male and females over 18 years of age.
- Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S-beta thallassemia genotype is required).
- Male and females African American subjects over 18 years of age.
- Exclusion of sickle cell disease (electrophoretic documentation of hemoglobin A is required).
Key exclusion criteria (6 listed)
- Hb A-only phenotype and sickle cell trait.
- Decisionally impaired subjects.
- Pregnant or lactating women
- Diagnosis of sickle cell disease (electrophoretic documentation of SS, or SC, or SB thallassemia genotype is required.)
- Decisionally impaired subjects.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To determine the prevalence and prognosis of secondary pulmonary hypertension in adult patients with sickle cell anemia.
Time frame: 10 years
predictive of any clinical outcome or response in sickle cell disease will provide preliminary evidence for further investigation
1 secondary outcome
To determine whether genetic polymorphisms in candidate genes contribute to its development or response to treatment.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Derived from this study: PubMed 41921073Li H, Gao S, Wang X, Asomaning N, Conrey A, Kruah B, Joo J, Wu CO, Sachdev V, Thein SL. Transthyretin V122I variant and protein affect cardiac severity and mortality in sickle cell disease. Blood Adv. 2026 Jun 9;10(11):4000-4008. doi: 10.1182/bloodadvances.2026019698.
- Derived from this study: PubMed 39659429Parrow NL, Doherty JM, Conrey A, Thein SL, Fleming RE. Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease. Adv Hematol. 2024 Dec 3;2024:9872440. doi: 10.1155/ah/9872440. eCollection 2024.
- Derived from this study: PubMed 34000072van Vuren AJ, Minniti CP, Mendelsohn L, Baird JH, Kato GJ, van Beers EJ. Lactate dehydrogenase to carboxyhemoglobin ratio as a biomarker of heme release to heme processing is associated with higher tricuspid regurgitant jet velocity and early death in sickle cell disease. Am J Hematol. 2021 Sep 1;96(9):E315-E318. doi: 10.1002/ajh.26243. Epub 2021 Jun 10. No abstract available.
- Derived from this study: PubMed 33506990Sachdev V, Tian X, Gu Y, Nichols J, Sidenko S, Li W, Beri A, Layne WA, Allen D, Wu CO, Thein SL. A phenotypic risk score for predicting mortality in sickle cell disease. Br J Haematol. 2021 Mar;192(5):932-941. doi: 10.1111/bjh.17342. Epub 2021 Jan 28.
- Derived from this study: PubMed 26589907Nguyen KL, Tian X, Alam S, Mehari A, Leung SW, Seamon C, Allen D, Minniti CP, Sachdev V, Arai AE, Kato GJ. Elevated transpulmonary gradient and cardiac magnetic resonance-derived right ventricular remodeling predict poor outcomes in sickle cell disease. Haematologica. 2016 Feb;101(2):e40-3. doi: 10.3324/haematol.2015.125229. Epub 2015 Nov 20. No abstract available.
- Derived from this study: PubMed 26576059Fitzhugh CD, Hsieh MM, Allen D, Coles WA, Seamon C, Ring M, Zhao X, Minniti CP, Rodgers GP, Schechter AN, Tisdale JF, Taylor JG 6th. Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia. PLoS One. 2015 Nov 17;10(11):e0141706. doi: 10.1371/journal.pone.0141706. eCollection 2015.
- Derived from this study: PubMed 25047658Wallen GR, Minniti CP, Krumlauf M, Eckes E, Allen D, Oguhebe A, Seamon C, Darbari DS, Hildesheim M, Yang L, Schulden JD, Kato GJ, Taylor JG 6th. Sleep disturbance, depression and pain in adults with sickle cell disease. BMC Psychiatry. 2014 Jul 21;14:207. doi: 10.1186/1471-244X-14-207.
- Derived from this study: PubMed 24224021Darbari DS, Wang Z, Kwak M, Hildesheim M, Nichols J, Allen D, Seamon C, Peters-Lawrence M, Conrey A, Hall MK, Kato GJ, Taylor JG 6th. Severe painful vaso-occlusive crises and mortality in a contemporary adult sickle cell anemia cohort study. PLoS One. 2013 Nov 5;8(11):e79923. doi: 10.1371/journal.pone.0079923. eCollection 2013.
- Derived from this study: PubMed 23065513Nekhai S, Xu M, Foster A, Kasvosve I, Diaz S, Machado RF, Castro OL, Kato GJ, Taylor JG 6th, Gordeuk VR. Reduced sensitivity of the ferroportin Q248H mutant to physiological concentrations of hepcidin. Haematologica. 2013 Mar;98(3):455-63. doi: 10.3324/haematol.2012.066530. Epub 2012 Oct 12.
- Derived from this study: PubMed 21630312Minniti CP, Taylor JG 6th, Hildesheim M, O'Neal P, Wilson J, Castro O, Gordeuk VR, Kato GJ. Laboratory and echocardiography markers in sickle cell patients with leg ulcers. Am J Hematol. 2011 Aug;86(8):705-8. doi: 10.1002/ajh.22065. Epub 2011 May 31.
- Derived from this study: PubMed 20335221Sundaram N, Tailor A, Mendelsohn L, Wansapura J, Wang X, Higashimoto T, Pauciulo MW, Gottliebson W, Kalra VK, Nichols WC, Kato GJ, Malik P. High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension. Blood. 2010 Jul 8;116(1):109-12. doi: 10.1182/blood-2009-09-244830. Epub 2010 Mar 24.
- Derived from this study: PubMed 19344390Kato GJ, Wang Z, Machado RF, Blackwelder WC, Taylor JG 6th, Hazen SL. Endogenous nitric oxide synthase inhibitors in sickle cell disease: abnormal levels and correlations with pulmonary hypertension, desaturation, haemolysis, organ dysfunction and death. Br J Haematol. 2009 May;145(4):506-13. doi: 10.1111/j.1365-2141.2009.07658.x. Epub 2008 Mar 17.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Swee Lay Thein, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pulmonary Hypertension and Sickle Cell Anemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites in United States.
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 6 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: finished, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the prevalence and prognosis of secondary pulmonary hypertension in adult patients with sickle cell anemia. (time frame: 10 years). 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 NCT00011648, which also lists 12 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 5 Nov 2026.