NHLBI TOPMed: Walk-PHaSST Sickle Cell Disease (SCD)

Walk-PHaSST study is a multi-center clinical trial to evaluate the effects of sildenafil on Sickle Cell Disease (SCD) population with low exercise capacity associated with an increased Doppler-estimated pulmonary artery systolic pressure (as assessed by the tricuspid regurgitant velocity (TRV)). It is a double-blind, placebo-controlled trial to assess the safety, tolerability, and efficacy of sildenafil in patients with SCD who had both an elevated TRV and decreased exercise capacity. The screening phase of the study enrolled 720 subjects and 74 of them were randomized for the clinical trial. For the screening cohort, we have collected general demographics and race/ethnicity, hemoglobin genotype, physical examination, laboratory screening, transthoracic Doppler echocardiography, and 6 minute walk test in 9 US and 1 UK site. The walk-PHaSST biorepository have banked samples from 610 of the screening subjects. A total of 592 subjects from the screening phase are included in the TOPMed program for WGS.]]>
TOPMed Whole Genome Sequencing Methods: Freeze 9TOPMed Whole Genome Sequencing Methods: Freeze 10Inclusion Criteria: Males or females, greater than or equal to 12 years of age and less than or equal to 70 years of age. Diagnosis of sickle cell disease (including, but not limited to SS, SC, SD, or S-beta zero thalassemia). Provision of informed consent and, where applicable, assent. Exclusion Criteria: Current pregnancy or lactation. Any one of the following medical conditions: Stroke within the last six weeks. Diagnosis of pulmonary embolism within the last three months. History of retinal detachment or retinal hemorrhage in the last 6 months. Non-arteritic anterior ischemic optic neuropathy (NAION) in one or both eyes. History of sustained priapism requiring medical or surgical treatment, unless currently impotent or on transfusion program within the last two years. Any unstable (chronic or acute) condition that in the opinion of the investigator will prevent completion of the study. Subjects taking nitrate-based vasodilators (including, but not limited to nicorandil [available in the UK only]), prostacyclin (inhaled, subcutaneous or intravenous) or endothelin antagonists. Subjects taking calcium channel blockers will be allowed to participate if they are on a stable dose for greater than or equal to 3 months. Left ventricular ejection fraction (LVEF) less than 40 percent or clinically significant ischemic, valvular or constrictive heart disease: LVEF less than 40 percent or SF less than 22 percent. Subjects in other research studies with investigational drugs (with the exception of hydroxyurea) unless the other trial has been approved by the walk-PHaSST Executive Committee for co-participation. Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements (in particular with 6MWT), e.g., angina pectoris, intermittent claudication, symptomatic hip osteonecrosis. Tonsillectomies for sleep apnea within 3 months prior to randomization. Active therapy for pulmonary hypertension, including prostacyclin analog, endothelin-1 antagonist, or PDE-5 inhibitor. Protease inhibitor therapy for HIV treatment Subjects taking potent CYP3A4 inhibitor therapy (e.g., itraconazole, ritonavir, ketoconazole) Subjects who are anticoagulated and have proliferative retinopathy (unless they have had ophthalmologist recommended intervention (e.g., phototherapy) or have been cleared by the ophthalmologist to participate in the study. Subjects with systolic blood pressure greater than or equal to 140 mmHg OR diastolic blood pressure greater than or equal to 90 mmHg. ]]>
Study Start Date: June 2007 Study Completion Date: October 2009 Results First Submitted: April 28, 2011 ]]>