Silent Cerebral Infarct Multi-Center Clinical Trial - Full Text View

Sponsor:	Washington University School of Medicine
Collaborator:	National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00072761

Purpose

The goal of this study is to determine the effectiveness of blood transfusion therapy for prevention of silent cerebral infarct (stroke) in children with sickle cell anemia.

Condition	Intervention	Phase
Sickle Cell Anemia Stroke	Procedure: transfusion therapy	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	Silent Cerebral Infarct Multi-Center Clinical Trial

Resource links provided by NLM:

Genetics Home Reference related topics: sickle cell disease

MedlinePlus related topics: Anemia Blood Transfusion and Donation Sickle Cell Anemia

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:

The primary outcome measurement is new or progressive cerebral infarction assessed by MRI of the brain or overt stroke. [ Time Frame: at entry into study and study exit ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	204
Study Start Date:	December 2004
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 blood transfusion therapy every 4-6 weeks for 36 months.	Procedure: transfusion therapy Those in the blood transfusion group will receive at least monthly blood transfusion therapy.
No Intervention: 2 observation group

Detailed Description:

Silent cerebral infarct (stroke) is the most common cause of severe cognitive impairments and related neurological functions in children with sickle cell anemia. Currently there exists no systemic strategy to identify or treat children with silent strokes.

The primary aim of this trial is to determine the effectiveness of blood transfusion therapy for the prevention of silent strokes in children with sickle cell anemia. This trial will also determine if blood transfusion therapy will prevent further cerebral injury and if the measured benefits of the therapy outweigh the risks associated with it.

Participants in this multi-center trial will be randomly assigned to one of 2 groups-the blood transfusion group or the observation group. Those in the blood transfusion group will receive at least monthly blood transfusion therapy. All participants will have history and physical examinations every 3 months, and magnetic resonance imaging (MRI) at the beginning of their entry into the study and at study exit.

Advances in the understanding and treatment of silent strokes will likely lead to a decrease in the burden associated with cerebral injury in children with sickle cell anemia and change the standard care for these children.

Eligibility

Ages Eligible for Study:	5 Years to 14 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION:

Patient must have sickle cell anemia (hemoglobin SS) or sickle beta thalassemia (hemoglobin SB) as confirmed at the local institution.
Participating institutions must submit documentation of the diagnostic hemoglobin analysis to the Statistical and Clinical Coordinating Centers to confirm the diagnosis of sickle cell anemia prior to randomization.
Patient must be 5 through 14 years of age.
Patient must have a cerebral infarct documented by MRI scan as read by the neuroradiology panel.
Informed consent with assent in accordance with the institutional policies (institutional IRB approval) and Federal guidelines (approved by the United States Department of Health and Human Services) must be signed by the patient's legally authorized guardian acknowledging written consent to join the study. When suitable, patients will be requested to give their assent to join the study.

EXCLUSION:

Patient with a history of a focal neurologic event lasting more than 24 hours with medical documentation or a history of prior overt stroke.
Patients with a transcranial doppler (TCD) study with a time-averaged mean velocity greater than 200 cm/sec verified by the study radiologist.
Patients with other neurological problems, such as neurofibromatosis, lead poisoning, or tuberous sclerosis.
Patients with HIV infection.
Pregnancy.
Patients who received treatment with anti-sickling drugs or hydroxyurea within 3 months or anticipate receiving anti-sickling drugs or hydroxyurea during the course of the study.
Abnormal kidney function (creatinine > 2x upper limit of normal).
Patients on chronic blood transfusion therapy for other reasons.
Patients judged not likely to be compliant by his/her hematologist and local nurse coordinator based on previous compliance in clinic appointments and following advice. Specifically, families that have missed at least two appointments without notification within 12 months prior to the trial or parents of potential patients that have been reported for medical or education neglect are not eligible for this trial.
Patients unable to receive blood transfusion because of alloimmunization.
Patients with permanent or semi-permanent metallic (braces on teeth) structures attached to their body. Such patients cannot obtain a MRI of the head to assess the presence of silent cerebral infarcts.
Siblings randomized in the trial.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00072761

Locations

United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:

Michael R. DeBaun, M.D.

Washington University School of Medicine

More Information

Additional Information:

official study website This link exits the ClinicalTrials.gov site

Publications:

Buchanan GR, DeBaun MR, Quinn CT, Steinberg MH. Sickle cell disease. Hematology Am Soc Hematol Educ Program. 2004;:35-47. Review.

Vendt BA, McKinstry RC, Ball WS, Kraut MA, Prior FW, Barton B, Casella JF, Debaun MR. Silent Cerebral Infarct Transfusion (SIT) Trial Imaging Core: Application of Novel Imaging Information Technology for Rapid and Central Review of MRI of the Brain. J Digit Imaging. 2008 Apr 9; [Epub ahead of print]

Casella JF, King AA, Barton B, White DA, Noetzel MJ, Ichord RN, Terrill C, Hirtz D, McKinstry RC, Strouse JJ, Howard TH, Coates TD, Minniti CP, Campbell AD, Vendt BA, Lehmann H, Debaun MR. Design of the silent cerebral infarct transfusion (SIT) trial. Pediatr Hematol Oncol. 2010 Mar;27(2):69-89.

Jordan LC, McKinstry RC 3rd, Kraut MA, Ball WS, Vendt BA, Casella JF, DeBaun MR, Strouse JJ; Silent Infarct Transfusion Trial Investigators. Incidental findings on brain magnetic resonance imaging of children with sickle cell disease. Pediatrics. 2010 Jul;126(1):53-61. Epub 2010 Jun 14.

Bhatnagar P, Purvis S, Barron-Casella E, Debaun MR, Casella JF, Arking DE, Keefer JR. Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients. J Hum Genet. 2011 Feb 17; [Epub ahead of print]

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Savage WJ, Barron-Casella E, Fu Z, Dulloor P, Williams L, Crain BJ, White DA, Jennings JM, Van Eyk JE, Debaun MR, Everett A, Casella JF. Plasma glial fibrillary acidic protein levels in children with sickle cell disease. Am J Hematol. 2011 May;86(5):427-9.

Williams LM, Fu Z, Dulloor P, Yen T, Barron-Casella E, Savage W, Van Eyk JE, Casella JF, Everett A. Hemoglobin depletion from plasma: considerations for proteomic discovery in sickle cell disease and other hemolytic processes. Proteomics Clin Appl. 2010 Dec;4(12):926-30.

Responsible Party:	Michael R. DeBaun, MD, MPH, Professor of Pediatrics, Biostatistics and Neurology, Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00072761 History of Changes
Other Study ID Numbers:	R01NS42804
Study First Received:	November 10, 2003
Last Updated:	March 2, 2011
Health Authority:	United States: Federal Government

Keywords provided by Washington University School of Medicine:

silent cerebral infarct
silent stroke
sickle cell anemia
stroke
transfusion therapy

Additional relevant MeSH terms:

Anemia
Anemia, Sickle Cell
Cerebral Infarction
Stroke
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn

Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on February 09, 2012