Secondary Pulmonary Hypertension in Adults With Sickle Cell Anemia

• ClinicalTrials.gov Identifier: NCT00011648
• Recruitment Status: Completed
• First Posted: February 26, 2001
• Last Update Posted: May 25, 2023
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Tracking Information

• First Submitted Date: February 24, 2001
• First Posted Date: February 26, 2001
• Last Update Posted Date: May 25, 2023
• Actual Study Start Date: February 19, 2008
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: April 30, 2019)

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

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures (submitted: August 22, 2014): To determine whether genetic polymorphisms in candidate genes contribute to its development or response to treatment. [ Time Frame: 1 year ]
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Secondary Pulmonary Hypertension in Adults With Sickle Cell Anemia
• Official Title: Determining the Prevalence and Prognosis of Secondary Pulmonary Hypertension in Adult Patients With Sickle Cell Anemia

Brief 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. 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 Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• 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)

Condition

• Pulmonary Hypertension
• Sickle Cell Anemia
• Sickle Cell Disease

• Intervention: Not Provided

Study Groups/Cohorts

• 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

Publications *

• van 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.
• Sachdev 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.
• Nguyen 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.
• Fitzhugh 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.
• Wallen 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.
• Darbari 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.
• Nekhai 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.
• Minniti 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.
• Sundaram 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.
• Kato 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 4, 2018): 986
• Original Enrollment (submitted: June 23, 2005): 800
• Study Completion Date: Not Provided
• Primary Completion Date: Not Provided

Eligibility Criteria

• INCLUSION CRITERIA FOR SICKLE CELL PATIENTS:
• 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).

EXCLUSION CRITERIA FOR SICKLE CELL PATIENTS:

• Hb A-only phenotype and sickle cell trait.
• Decisionally impaired subjects.
• Pregnant or lactating women

INCLUSION CRITERIA FOR CONTROL SUBJECTS:

• Male and females African American subjects over 18 years of age.
• Exclusion of sickle cell disease (electrophoretic documentation of hemoglobin A is required).

EXCLUSION CRITERIA FOR CONTROL SUBJECTS:

• Diagnosis of sickle cell disease (electrophoretic documentation of SS, or SC, or SB thallassemia genotype is required.)
• Decisionally impaired subjects.
• Pregnant or lactating women

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00011648
• Other Study ID Numbers: 010088; 01-H-0088
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Original Study Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Swee Lay Thein, M.D.; National Heart, Lung, and Blood Institute (NHLBI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: January 24, 2023