Nctid:
NCT00001716
Payload:
{"hasResults"=>false, "derivedSection"=>{"miscInfoModule"=>{"versionHolder"=>"2024-09-05"}, "conditionBrowseModule"=>{"meshes"=>[{"id"=>"D000000740", "term"=>"Anemia"}, {"id"=>"D000000755", "term"=>"Anemia, Sickle Cell"}, {"id"=>"D000002637", "term"=>"Chest Pain"}], "ancestors"=>[{"id"=>"D000006402", "term"=>"Hematologic Diseases"}, {"id"=>"D000010146", "term"=>"Pain"}, {"id"=>"D000009461", "term"=>"Neurologic Manifestations"}, {"id"=>"D000000745", "term"=>"Anemia, Hemolytic, Congenital"}, {"id"=>"D000000743", "term"=>"Anemia, Hemolytic"}, {"id"=>"D000006453", "term"=>"Hemoglobinopathies"}, {"id"=>"D000030342", "term"=>"Genetic Diseases, Inborn"}], "browseLeaves"=>[{"id"=>"M4085", "name"=>"Anemia, Sickle Cell", "asFound"=>"Sickle Cell Anemia", "relevance"=>"HIGH"}, {"id"=>"M27137", "name"=>"Respiratory Aspiration", "relevance"=>"LOW"}, {"id"=>"M13066", "name"=>"Pain", "relevance"=>"LOW"}, {"id"=>"M4070", "name"=>"Anemia", "asFound"=>"Anemia", "relevance"=>"HIGH"}, {"id"=>"M5882", "name"=>"Chest Pain", "asFound"=>"Chest Pain", "relevance"=>"HIGH"}, {"id"=>"M9490", "name"=>"Hematologic Diseases", "relevance"=>"LOW"}, {"id"=>"M12404", "name"=>"Neurologic Manifestations", "relevance"=>"LOW"}, {"id"=>"M9547", "name"=>"Hemolysis", "relevance"=>"LOW"}, {"id"=>"M4073", "name"=>"Anemia, Hemolytic", "relevance"=>"LOW"}, {"id"=>"M4075", "name"=>"Anemia, Hemolytic, Congenital", "relevance"=>"LOW"}, {"id"=>"M9539", "name"=>"Hemoglobinopathies", "relevance"=>"LOW"}, {"id"=>"M23686", "name"=>"Genetic Diseases, Inborn", "relevance"=>"LOW"}, {"id"=>"T5229", "name"=>"Sickle Cell Anemia", "asFound"=>"Sickle Cell Anemia", "relevance"=>"HIGH"}], "browseBranches"=>[{"name"=>"Blood and Lymph Conditions", "abbrev"=>"BC15"}, {"name"=>"Diseases and Abnormalities at or Before Birth", "abbrev"=>"BC16"}, {"name"=>"All Conditions", "abbrev"=>"All"}, {"name"=>"Respiratory Tract (Lung and Bronchial) Diseases", "abbrev"=>"BC08"}, {"name"=>"Symptoms and General Pathology", "abbrev"=>"BC23"}, {"name"=>"Nervous System Diseases", "abbrev"=>"BC10"}, {"name"=>"Rare Diseases", "abbrev"=>"Rare"}]}, "interventionBrowseModule"=>{"meshes"=>[{"id"=>"D000009569", "term"=>"Nitric Oxide"}, {"id"=>"D000005996", "term"=>"Nitroglycerin"}], "ancestors"=>[{"id"=>"D000001993", "term"=>"Bronchodilator Agents"}, {"id"=>"D000001337", "term"=>"Autonomic Agents"}, {"id"=>"D000018373", "term"=>"Peripheral Nervous System Agents"}, {"id"=>"D000045505", "term"=>"Physiological Effects of Drugs"}, {"id"=>"D000018927", "term"=>"Anti-Asthmatic Agents"}, {"id"=>"D000019141", "term"=>"Respiratory System Agents"}, {"id"=>"D000016166", "term"=>"Free Radical Scavengers"}, {"id"=>"D000000975", "term"=>"Antioxidants"}, {"id"=>"D000045504", "term"=>"Molecular Mechanisms of Pharmacological Action"}, {"id"=>"D000018377", "term"=>"Neurotransmitter Agents"}, {"id"=>"D000045462", "term"=>"Endothelium-Dependent Relaxing Factors"}, {"id"=>"D000014665", "term"=>"Vasodilator Agents"}, {"id"=>"D000064426", "term"=>"Gasotransmitters"}, {"id"=>"D000020011", "term"=>"Protective Agents"}], "browseLeaves"=>[{"id"=>"M207501", "name"=>"Chrysarobin", "relevance"=>"LOW"}, {"id"=>"M9102", "name"=>"Nitroglycerin", "asFound"=>"Brochure", "relevance"=>"HIGH"}, {"id"=>"M12507", "name"=>"Nitric Oxide", "asFound"=>"Adhesive", "relevance"=>"HIGH"}, {"id"=>"M5269", "name"=>"Bronchodilator Agents", "relevance"=>"LOW"}, {"id"=>"M20963", "name"=>"Anti-Asthmatic Agents", "relevance"=>"LOW"}, {"id"=>"M21137", "name"=>"Respiratory System Agents", "relevance"=>"LOW"}, {"id"=>"M4292", "name"=>"Antioxidants", "relevance"=>"LOW"}, {"id"=>"M20504", "name"=>"Neurotransmitter Agents", "relevance"=>"LOW"}, {"id"=>"M25496", "name"=>"Endothelium-Dependent Relaxing Factors", "relevance"=>"LOW"}, {"id"=>"M17412", "name"=>"Vasodilator Agents", "relevance"=>"LOW"}, {"id"=>"M21869", "name"=>"Protective Agents", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"Anti-Inflammatory Agents", "abbrev"=>"Infl"}, {"name"=>"Antirheumatic Agents", "abbrev"=>"ARhu"}, {"name"=>"Analgesics", "abbrev"=>"Analg"}, {"name"=>"All Drugs and Chemicals", "abbrev"=>"All"}, {"name"=>"Vasodilator Agents", "abbrev"=>"VaDiAg"}, {"name"=>"Respiratory System Agents", "abbrev"=>"Resp"}]}}, "protocolSection"=>{"designModule"=>{"phases"=>["PHASE2"], "studyType"=>"INTERVENTIONAL", "designInfo"=>{"primaryPurpose"=>"TREATMENT"}, "enrollmentInfo"=>{"count"=>58}}, "statusModule"=>{"overallStatus"=>"COMPLETED", "startDateStruct"=>{"date"=>"1998-07"}, "expandedAccessInfo"=>{"hasExpandedAccess"=>false}, "statusVerifiedDate"=>"2003-07", "completionDateStruct"=>{"date"=>"2003-07"}, "lastUpdateSubmitDate"=>"2008-03-03", "studyFirstSubmitDate"=>"1999-11-03", "studyFirstSubmitQcDate"=>"1999-11-03", "lastUpdatePostDateStruct"=>{"date"=>"2008-03-04", "type"=>"ESTIMATED"}, "studyFirstPostDateStruct"=>{"date"=>"1999-11-04", "type"=>"ESTIMATED"}}, "conditionsModule"=>{"keywords"=>["Hemoglobin", "P50", "Microvascular", "Perfusion", "Magnetic Resonance Imaging", "Sickle Cell Anemia"], "conditions"=>["Chest Pain", "Sickle Cell Anemia"]}, "referencesModule"=>{"references"=>[{"pmid"=>"9287233", "type"=>"BACKGROUND", "citation"=>"Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997 Sep 11;337(11):762-9. doi: 10.1056/NEJM199709113371107. No abstract available."}, {"pmid"=>"9276736", "type"=>"BACKGROUND", "citation"=>"Head CA, Brugnara C, Martinez-Ruiz R, Kacmarek RM, Bridges KR, Kuter D, Bloch KD, Zapol WM. Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo. J Clin Invest. 1997 Sep 1;100(5):1193-8. doi: 10.1172/JCI119631."}, {"pmid"=>"9428761", "type"=>"BACKGROUND", "citation"=>"Gow AJ, Stamler JS. Reactions between nitric oxide and haemoglobin under physiological conditions. Nature. 1998 Jan 8;391(6663):169-73. doi: 10.1038/34402."}]}, "descriptionModule"=>{"briefSummary"=>"Sickle cell anemia is the most common genetic disease affecting African-Americans. About 1 in every 1000 African-Americans has the disease and 1 in every 12 carry the genes that could be passed on to their children. People with sickle cell anemia have abnormal hemoglobin, the molecules responsible for carrying oxygen in the blood. The abnormal hemoglobin can cause damage to the red blood cells. The damaged red blood cell may then stick in the blood vessels and cause pain and injury to organs. Some of the complications caused by the sticking of blood cells are called acute pain crisis and acute chest syndrome (ACS).\n\nNitric oxide (NO) is a gas that has been proposed as a possible therapy for the ACS complication of sickle cell anemia. Studies have shown that NO may favorably affect sickle cell hemoglobin molecules, thereby improving blood flow through small vessels.\n\nThis study is designed to evaluate the effects of NO, when taken in combination with a drug called nitroglycerin on patients with sickle cell anemia and normal volunteers. The effects of these two drugs only last while the patient is receiving them. Researchers hope the information learned from this study will help to develop new therapies for sickle cell anemia.", "detailedDescription"=>"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 and acute chest syndrome (ACS) are common complications of sickle cell anemia. Inhaled nitric oxide (NO) has been proposed as a possible therapy for the ACS. Anecdotally, NO has been described to rapidly improve the hypoxemia and the clinical course of the ACS. Furthermore, a number of recent studies have suggested that NO may have a favorable impact on sickle hemoglobin at the molecular level and could improve the abnormal microvascular perfusion that is characteristic of sickle cell anemia.\n\nThis clinical trial is designed to evaluate the physiologic and molecular effects of inhaled NO and a currently available, safe, FDA-approved medication, nitroglycerin, that is a nitric oxide donor (i.e., a source of NO after metabolism in the body), in study subjects with and without sickle cell anemia. Whole blood will be analyzed to characterize the metabolism of NO and NO donors, the molecular interactions between hemoglobin and NO, the duration of effect of these therapies on hemoglobin oxygen affinity and other properties of the erythrocyte and intracellular hemoglobin (including the solubility of deoxy sickle hemoglobin).\n\nWe also plan to characterize the effect of NO delivery on microvascular perfusion in study subjects with and without sickle cell anemia. Measurements in study subjects will be made prior to and while receiving either NO, nitroglycerin, or placebo. These perfusion measurements will occur at rest and during concentric dorsiflexion exercise. Magnetic resonance imaging (MRI) of lower extremity skeletal muscle enhancement during first passage of intravenously injected gadolinium contrast will be used to evaluate regional skeletal muscle perfusion. Perfusion measurements will be paired with a \\[31\\]Phosphorus Magnetic Resonance Spectroscopy (\\[31\\]P-MRS) study of the concentration of muscle high energy phosphate compounds. Changes in their levels reflect the energy state of muscle and are dependent on the adequacy of blood flow.\n\nThis study will allow three major assessments: firstly, the characterization of the microvascular perfusion at rest and during exercise in study subjects with sickle cell anemia. Secondly, the effects of NO on red cell and hemoglobin function and skeletal muscle perfusion in normal study subjects (without sickle cell anemia), and finally, the effects of NO on red cell and hemoglobin function and skeletal muscle perfusion in study subjects with sickle cell anemia. Our hypothesis is that one or more of these effects could be of potential therapeutic benefit to sickle cell anemia patients."}, "eligibilityModule"=>{"sex"=>"ALL", "stdAges"=>["CHILD", "ADULT", "OLDER_ADULT"], "healthyVolunteers"=>true, "eligibilityCriteria"=>"INCLUSION CRITERIA:\n\nMales or females 18 to 65 years of age.\n\nDiagnosis of sickle cell disease (electrophoretic documentation of SS homozygosity is required) or identification as a normal volunteer.\n\nHematocrit greater than 18% (with an absolute reticulocyte count greater than 100,000/ml).\n\nHematocrit 18-21% (with an absolute reticulocyte count greater than 100,000/ml): Only 100 ml of blood may be drawn. The study subject may be re-entered in the study after four weeks (with repeat full screening labs).\n\nEXCLUSION CRITERIA:\n\nClinically unstable sickle cell anemia defined by the following:\n\nHaving greater than two acute pain crises in the last two months; on hydroxyurea or butyrate therapy any time in the last 12 months; or blood transfusion within last three months, or % hemoglobin A greater than 20%.\n\nAge less than 18 years or greater than 65 years.\n\nCurrent pregnancy or lactation.\n\nInability to exercise the anterior tibialis muscle.\n\nActive cigarette smoker-defined as the inhalation of smoke from any tobacco product in the last one month.\n\nMedical conditions: diabetes mellitus; coronary artery disease; peripheral vascular disease; migraine headaches in the last 12 months; history of previous CVA or stroke; or creatinine greater than 1.0 mg/dL.\n\nMRI Exclusions: cardiac pacemaker or implantable defibrillator; aneurysm clip; neural stimulator (e.g. TENS-Unit); any type of ear implant; or metal in the eye (e.g. from machining); any implanted device (e.g. insulin pump, drug infusion device); or any metallic foreign body, shrapnel, or bullet.\n\nHematocrit less than or equal to 18 percent: will not be eligible for the study; may return for evaluation at a later date.\n\nNo aspirin or non-steroidal anti-inflammatory drugs (no NSAIDS and caffeine the day of the study.) Patients on opiates and acetaminophen will not be excluded.\n\nPatients taking Viagra will be excluded from the study."}, "identificationModule"=>{"nctId"=>"NCT00001716", "briefTitle"=>"Effects of Nitric Oxide and Nitroglycerin in Patients With Sickle Cell Anemia", "organization"=>{"class"=>"NIH", "fullName"=>"National Institutes of Health Clinical Center (CC)"}, "officialTitle"=>"Physiologic Effects of Inhaled Nitric Oxide, Nitroglycerin, and Placebo in Study Subjects With Sickle Cell Anemia", "orgStudyIdInfo"=>{"id"=>"980129"}, "secondaryIdInfos"=>[{"id"=>"98-CC-0129"}]}, "armsInterventionsModule"=>{"interventions"=>[{"name"=>"Nitric Oxide", "type"=>"DRUG"}, {"name"=>"Nitroglycerin", "type"=>"DRUG"}]}, "contactsLocationsModule"=>{"locations"=>[{"zip"=>"20892", "city"=>"Bethesda", "state"=>"Maryland", "country"=>"United States", "facility"=>"Warren G. Magnuson Clinical Center (CC)", "geoPoint"=>{"lat"=>38.98067, "lon"=>-77.10026}}]}, "sponsorCollaboratorsModule"=>{"leadSponsor"=>{"name"=>"National Institutes of Health Clinical Center (CC)", "class"=>"NIH"}}}}
