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Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension Clinical Trials Information presented on Clinical Trials Search isn't intended to be a substitute for proven healthcare advice, trips or treatment using a real physician. We are not docs. Always confer with your mD on Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension conditions. Clinical Trials Search.org is a site dedicated to listing clinical research studies in human subjects. Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension Clinical research trials and Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension medical trials take place in hundreds of localities across the U.S.. A clinical trial or clinical study is a research project with human volunteer subjects. Clinical drug trials and pharmaceutical clinical trials usually measure the effectiveness of new drugs. The intention of the studies / projects is to resolve certain human health questions. Clinical trials are a popular means for physicians, government agencies, and private sector corporations to detect remedies for all forms of circumstances, like Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension. Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension Clinical Trials and other clinical trials allow for volunteers to undergo healthcare treatment options before they are available to the masses. Most times the participants receive treatment for free, and every now and again they are paid for their time. Occasionally there is a cost for a Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension clinical trial. Subjects typically recieve the finest healthcare available for their Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension condition. Hazards are a reality, nonetheless, and might include more or frequent mD trips, health risks (potentially life-endangering), and/or the treatment being ineffective. Trials are federally regulated with stern guidelines to protect clinical trials subjects.
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Home > "I" Clinical Trials Conditions > Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension  Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension
Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension
For Condition: Pulmonary Hypertension,Sickle Cell Anemia
Status: Recruiting
Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) ,
Synopsis: This study will test whether inhaling nitric oxide gas mixed with room air can improve pulmonary hypertension (high blood pressure in the lungs) in patients with sickle cell anemia. It is estimated that 20 to 30 percent of patients with sickle cell anemia have moderate to severe pulmonary hypertension, a disease complication associated with higher rates of illness and death. Patients with sickle cell disease 18 years of age or older may be eligible to participate in one or more parts of this three-stage study. Candidates will be screened with a medical history, physical examination, electrocardiogram, echocardiogram and blood tests. Those enrolled will undergo the following tests and procedures: Stage 1: Patients will be tested to determine the cause of pulmonary hypertension. They will have an echocardiogram (ultrasound study of the heart); a test for asthma, with measurement of arterial blood oxygen levels; oxygen breathing study with measurement of arterial blood oxygen levels; chest X-ray; computed tomography (CT) scans of the lung with and without contrast material; magnetic resonance imaging (MRI) of the heart; 6-minute walk to measure the distance covered in that time at a comfortable pace; night-hawks oxygen measurement while sleeping; blood tests for HIV, hepatitis virus, lupus and arthritis and pregnancy; pulmonary ventilation/perfusion scan with evaluation of shunt fraction to the brain and kidney; and exercise studies will be performed to determine oxygen and carbon dioxide consumption and production and to measure the anaerobic threshold. Stage 2: Patients who proceed with stage 2 will have a detailed MRI evaluation of the heart and will be admitted to the Clinical Center intensive care unit for the following procedure: A small intravenous (IV) catheter (plastic tube) is placed in the patient arm and a longer tube, called a central line, in a deeper neck or leg vein. A long thin tube is then inserted through the vein into the heart and the lung artery to measure all blood pressures in the heart and lungs directly. Following baseline measurements the following medications will be delivered for two hours each, separated by a 30 minute wash-out period. The patients is then given oxygen to breathe for 2 hours, followed by infusion of prostacyclin, a blood pressure-lowering drug, for 2 hours; and finally inhaled nitric oxide for 2 hours. A small blood sample (3 tablespoons) of blood is drawn during the nitric oxide administration. Stage 3: For patients who complete stage II or III and do not respond to NO gas as determined by a decrease in mean or systolic pulmonary artery pressure of greater than 10% from baseline or a 10% increase in 6 minute walk distance, or are unable to receive it due to technical, regulatory (no free standing home structure for storage of NO gas, etc.) or personal lifestyle issues (some patient do not want to carry two tanks of gas - oxygen and NO - or have difficulty learning how to use the NO gas system), we will offer regular exchange transfusions and home oxygen for three months with a goal of maintaining hemoglobin levels of 8-10 and hemoglobin S levels of less than 40%. The monitoring of patients receiving exchange transfusions will be the same as for the patients receiving NO gas: Measurements will include pulmonary artery pressure measured by repeat right heart catheterization, other hemodynamic parameters, exercise tolerance by 6-minute walk, plasma adhesion molecule levels, neutrophil and monocyte mRNA gene profiles, and circulating erythroid progenitor cell a/a hemoglobin message and protein levels. This portion of the study is to be undertaken as an outpatient. Clinical follow-up will involve bi-weekly clinic visits with the principal investigator, associate investigators, or study nurse. At these clinic visits venous blood will be obtained for hemoglobin electrophoresis (including hemoglobin F and A2), CBC, ESR, C-reactive protein and standard chemistries. Research blood, for plasma and erythrocyte reactive nitrogen species and plasma adhesion molecule levels, will be collected with total blood drawn per day not to exceed 30 mL. Protocol nurse or principal investigator will record total weekly symptoms, emergency room visits, hospital admissions, and narcotic use. Echocardiograms and 6-minute walk will be repeated at two-week intervals. 32 mL of blood will be drawn prior to the exchange transfusion and a 4 and 8 weeks for neutrophil and monocyte mRNA expression chip profiling. Patients who develop any complication of their disease (i.e. vaso-occlusive crisis, acute chest syndrome, let ulcers, priapism, avascular necrosis of the femoral hip, asthma, etc.) will be strongly encouraged to directly come to the Clinical Center's 10D ICU for evaluation and direct admission by the 10D ICU physician on-call. If they are very ill they will be instructed to either call and ambulance or go to the nearest emergency room. If they are relatively stable, patients will be instructed to call the 10D ICU and speak with the physician on-call. We will follow patients according to the NO protocol with right heart catheterization at 3 months of therapy and serial echocardiograms. The effects of exchange transfusion will be statistically analyzed separately but in a similar fashion as delineated for NO treatment. All patients will complete Stage I and II of the study prior to entering into Exchange Transfusion therapy. Patients with greater than a 10% increase in six-minute walk distance or a 10% reduction in mean or systolic pulmonary artery pressures, who want to continue Exchange Transfusion therapy will have the option of continuing therapy. In these cases, blood draws and clinical follow-up will be reduced to bi-monthly intervals and when clinically indicated. The Clinical Center will continue to pay for these clinic visits and urgent care at the Clinical Center. The Transfusion Therapy and the Clinical Center care will continue until the study has terminated (anticipated three year study duration). Our physicians and social workers will work with patients to help them obtain appropriate insurance to cover Exchange Transfusion therapy. However, it is possible that circumstances may arise that prevent the patient from continuing this therapy after the study is terminated. Alternative Therapies Patients who have enrolled in the NO or transfusion treatment arm of the study who do not respond to the treatment (defined by a 10% reduction in mean or systolic pulmonary artery pressure measured by right heart catheterization or a 10% increase in 6-minute walk distance) will be eligible to receive the alternative therapy (NO or transfusion) or other FDA approved medications. These medications may include oxygen, prostacyclin (flolan or remodulin), L-arginine, bosentan or sidenafil. We will limit the number of patients who are treated with medication other than NO or exchange transfusion to 10 subjects. Such patients will be managed at the NIH, in collaboration with their primary medical providers, according to accepted current standards of care using only FDA approved medication. The effect of such treatments on estimated pulmonary artery pressures, measured by echocardiogram, and on 6-minute walk distance will be assessed at regular intervals (every 1-3 months while on protocol) and all adverse events reported to the IRB and DSMB as defined by the current protocol. Patients maintained on alternative therapies will not have research bloods drawn, all laboratory testing will be obtained only for clinical indications. Such patients may be managed on this protocol until the protocol is terminated, the medication used becomes FDA approved specifically for use in sickle cell disease, the patient wishes to end participation, or the patient wishes to enroll in another study for treatment of pulmonary hypertension.
Details: 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. Inhaled nitric oxide (NO) has been proposed as a possible therapy for both primary and secondary pulmonary hypertension. Furthermore, a number of recent studies have suggested that NO may have a favorable impact on sickle red cells at the molecular level and could improve the abnormal microvascular perfusion that is characteristic of sickle cell anemia. This clinical trial is designed (1) to determine the pathophysiologic processes that are associated with and potentially contribute to secondary pulmonary hypertension in adult patients with sickle cell anemia (2) to determine the relative acute vasodilatory effects of oxygen, intravenous prostacyclin, and inhaled nitric oxide on pulmonary artery pressures and other hemodynamic parameters in patients with secondary pulmonary hypertension and sickle cell anemia, and (3) to determine the effects of two months of inhaled nitric oxide on pulmonary artery pressures, other hemodynamic parameters, exercise tolerance, and symptoms in this patient population.
Eligibility:
Study Type: Interventional, Treatment, Safety
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA For Stage I for Pulmonary Hypertension Subjects: Male or female, 18 years of age or older. Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S beta-halassemia genotype is required). Hematocrit greater than 18% (with an absolute reticulocyte count greater than 100,000/ml if hematocrit is 18-24%). Mild to severe pulmonary hypertension with systolic pulmonary artery pressures greater than or equal to 30 mm Hg (tricuspid regurgitant velocity greater than 2.5 m/sec, assuming right atrial pressure greater than 5 cm H20) or right ventricular enlargement. We will compare these studies to a control group of sickle cell patients that do not have pulmonary hypertension. For Stage I Controls: Males or females, 18 years of age or older. Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S beta-halassemia genotype is required). Hematocrit greater than 18% (with an absolute reticulocyte count greater than 100,000/ml if hematocrit is 18-24%). Tricuspid regurgitant velocity less than or equal to 2.4 m/sec, matched for age, gender, hydroxyurea therapy status and fetal hemoglobin levels with the pulmonary hypertension subjects. For Stage II: Male or female, 18 years of age or older. Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S beta-thalassemia genotype is required). Hematocrit greater than 18% (with an absolute reticulocyte count greater than 100,000/ml if hematocrit is 18-24%). Mild to severe pulmonary hypertension with systolic pulmonary artery pressures greater than or equal to 30 mm Hg (tricuspid regurgitant velocity greater than 2.5 m/sec, assuming right atrial pressure greater than 5 cm H20) or right ventricular enlargement. For Stage III: Male or female, 18 years of age or older. Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S beta-thalassemia genotype is required). Hematocrit greater than 18 % (with an absolute reticulocyte count greater than 100,000/ml if hematocrit is 18-24%). Able to walk at least 100 m in six minutes at baseline. Mild to severe pulmonary hypertension with mean pulmonary artery pressures greater than or equal to 25 mm Hg, measured by pulmonary artery catheterization. Pulmonary artery wedge pressure or left ventricular end-diastolic pressure less than or equal to 18 mm Hg or echocardiographic criteria to exclude left ventricular dysfunction. EXCLUSION CRITERIA For Stage I Current pregnancy or lactation For Stage II Current pregnancy or lactation Any of the following medical conditions: Significant renal insufficiency (patient on hemodialysis or estimated creatinine clearance less than 30%of normal; Stroke within the last six weeks; New diagnosis of pulmonary embolism within the last three months; History of retinal detachment. Hematocrit less than 18 % will not be eligble for the study; may return for evaluation at a later date. Patients taking prostacyclin (inhaled or intravenous) will be excluded from the study. Patients taking calcium channel blockers will be allowed to participate provided they are on a stable dose for greater than one month. For Stage III Current pregnancy or lactation Any of the following medical conditions: Significant renal insufficiency (patient on hemodialysis or estimated creatinine clearance less than 30%of normal; Stroke within the last six weeks; Left ventricular end-diastolic pressure greater than or equal to 18 mm Hg (determined by the pulmonary artery occlusion pressure) or echocardiographic criteria for left ventricular dysfunction; New diagnosis of pulmonary embolism within the last three months; History of retinal detachment; Hematocrit less than 18 % will not be eligble for the study; may return for evaluation at a later date. Patients taking prostacyclin (inhaled or intravenous) will be excluded from the study. Patients taking calcium channel blockers will be allowed to participate provided they are on a stable dose for greater than one month. Patients who are in other research studies for the treatment of pulmonary hypertension or who are on treatment specific for pulmonary hypertension will be excluded from stage III of this study.
Total Enrollment: 300
Location and Contact Information:
National Heart, Lung and Blood Institute (NHLBI) *Recruiting*
Bethesda, Maryland, 20892
United States
Recruiting Patient and Public Liaison Office 1-800-411-1222
Additional Information:
Study ID Numbers: 010223; 01-H-0223
Study Start Date: July 27, 2001
Record last reviewed: June 19, 2003
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00023296
Other Sickle Cell Anemia Studies:
1. Study of Clotrimazole and Hydroxyurea in Patients With Sickle Cell Syndromes
2. Study of Allogeneic Bone Marrow Transplantation Using Matched, Related Donors in Patients With Nonmalignant Hematologic Disorders
3. Bone Marrow transplant from related donor for patients with high risk hemoglobinopathies
4. Collection and Storage of Umbilical Cord Stem Cells for Treatment of Sickle Cell Disease
5. Hydroxyurea for the Treatment of Patients with Sickle Cell Anemia
Related Studies:
Other Sickle Cell Anemia Clinical Trials
Other Maryland Clinical Trials
Other Bethesda Clinical Trials
Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension
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