Ignite Creation Date:
2024-05-05 @ 4:59 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00367523
Status:
COMPLETED
Last Update Posted:
2019-11-29
First Post:
2006-08-22
Brief Title:
Pulmonary Hypertension in Patients With Sickle Cell Disease in Nigeria
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Prevalence of Secondary Arterial Hypertension PAH in Patients With Sickle Cell Disease in Nigeria and the Role of HIVAIDS and Endemic Parasitic Infections in the Natural History of Pulmonary Hypertension in Sickle Cell Disease
Status:
COMPLETED
Status Verified Date:
2017-09-28
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:
This study will explore how people with sickle cell disease SCD develop a complication called pulmonary hypertension PHTN a serious disease in which blood pressure in the lungs is higher than normal PHTN is also caused by HIV hepatitis C and schistosomiasis Patients who have both SCD and one of these other infections may develop more severe PHTN The number of Nigerians with SCD who also have PHTN is not known nor is the cause of PHTN in this population This study will examine genetic material in people with and without SCD to determine whether certain genes will allow doctors to predict which patients with SCD are likely to develop PHTN
Nigerian males and females 10 years of age and older with or without SCD may be eligible for this study Patients must have SS SC or SB thalassemia or other genotype control subjects must have hemoglobin A or AS genotype
Participants undergo a complete medical history and physical examination blood tests electrocardiogram EKG ultrasound tests of the heart and abdomen and a 6-minute walk distance test to determine exercise capacity Blood tests include screening for HIV hepatitis B and C schistosomiasis hookworm and malaria Patients who test positive for HIV hepatitis B or C schistosomiasis hookworm or malaria are referred for treatment at Ahmadu Bello University Teaching Hospital in Zaria Nigeria and those who test negative for hepatitis B are referred for vaccination Genetic tests focus on genes involved in SCD PHTN inflammation blood vessel function and red blood cell function
Nigerian males and females 10 years of age and older with or without SCD may be eligible for this study Patients must have SS SC or SB thalassemia or other genotype control subjects must have hemoglobin A or AS genotype
Participants undergo a complete medical history and physical examination blood tests electrocardiogram EKG ultrasound tests of the heart and abdomen and a 6-minute walk distance test to determine exercise capacity Blood tests include screening for HIV hepatitis B and C schistosomiasis hookworm and malaria Patients who test positive for HIV hepatitis B or C schistosomiasis hookworm or malaria are referred for treatment at Ahmadu Bello University Teaching Hospital in Zaria Nigeria and those who test negative for hepatitis B are referred for vaccination Genetic tests focus on genes involved in SCD PHTN inflammation blood vessel function and red blood cell function
Detailed Description:
Sickle cell disease SCD is an autosomal recessive disorder and the most common genetic disease in the world SCD is the most common inherited blood disorder in the United States affecting 70000 to 80000 Americans Secondary pulmonary arterial hypertension PAH has been shown to have a prevalence of 30 in patients with SCD with mortality rates of 40 at 40 months after diagnosis in the United States The burden of disease of SCD is highest in Nigeria West Africa where approximately 4 of the 140 million people in that country are homozygous for SCD but the prevalence and outcomes of pulmonary hypertension in Africa have not been investigated Many known infectious risk factors for PAH are also highly prevalent in Nigeria including Human Immuno Deficiency VirusAcquired Immune Deficiency Syndrome HIVAIDS malaria chronic hepatitis B and C schistosomiasis and hookworm Our first clinical hypothesis is that interactions between these infectious complications and sickle cell related hemolysis would lead to an even higher prevalence of PAH in Nigeria Our study is therefore designed to determine the prevalence of PAH in Nigerian patients with SCD using echocardiographic measurements of the tricuspid regurgitant jet velocity We aim to determine the associations and epidemiological interactions that might lead to PAH of endemic infectious disease co-morbidities especially HIVAIDS with SCD by screening for these infectious diseases in control subjects and in SCD patients with and without PAH Our second translational hypothesis is that genetic polymorphisms in candidate genes that regulate endothelial function and adhesion contribute to the development of PAH phenotype in African SCD patients Using both candidate gene and genome wide association approaches we will identify and selectively characterize single nucleotide polymorphisms SNPs in genes important for endothelial function vascular inflammation and cardiac function functional VCAM1 SNPs and steady state soluble VCAM-1 levels SELP SELE SELL ICAM1 ITGA4 and CD36 TGF-Beta superfamily gene polymorphisms - specifically bone morphogenic protein receptor II and CORIN the serine protease which cleaves the natriuretic peptide precursors secreted by the heart proANP and proBNP to the physiologically active ANP and BNP Finally our study using the SELDI-TOF-MS system and 2D differential gel electrophoresis DIGE will examine differential patterns of plasma protein expression in particular the apolipoproteins and arginase I and II enzymes as potential biomarkers or therapeutic targets in sickle cell patients with pulmonary hypertension Our proposal uniquely integrates international clinical epidemiologic and molecular studies to determine the burden of SCD related PAH decipher the mechanism of interactions of PAH and infectious diseases and identify genetic and protein markers and potential therapeutic targets for PAH Our collaboration will provide an opportunity for the rapid transfer of appropriate technology and knowledge relevant to the provision of the highest quality care to sickle cell patients in Nigeria and the world
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 |
|---|---|---|---|
| 06-H-N189 | None | None | None |