Examining Cognitive Function and Brain Abnormalities in Adults With Sickle Cell Disease - Pilot Intervention Study - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00850018

Purpose

Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease that can cause intense pain episodes and may lead to organ failure. Preliminary studies have shown that adults with SCD may have brain abnormalities that contribute to problems with cognitive functioning, including attention and memory difficulties. This study will use brain magnetic resonance imaging (MRI) and neuropsychological testing to examine the differences in cognitive functioning in adults with SCD who are treated for anemia with monthly blood transfusions for 6 months versus adults with SCD who receive usual care for 6 months.

Condition	Intervention	Phase
Anemia, Sickle Cell	Procedure: Monthly blood transfusion regimen Behavioral: Usual care	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Neuropsychological Dysfunction and Neuroimaging Abnormalities in Neurologically Intact Adults With Sickle Cell Disease - A Pilot Intervention Study

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 National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Cognitive function [ Time Frame: Measured at Month 6 ] [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	December 2004
Study Completion Date:	December 2010
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Participants will receive monthly blood transfusions.	Procedure: Monthly blood transfusion regimen Participants will receive blood transfusions at 3- to 4-week intervals for 6 months for the treatment of SCD-related anemia; the total number of transfusions that participants will receive will vary between six and eight. Other Name: Chronic transfusion therapy
Active Comparator: 2 Participants will receive usual care.	Behavioral: Usual care Participants will receive usual care for the treatment of SCD. Other Name: Standard care alone, guided by disease symptoms.

Detailed Description:

SCD is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and intense episodes of pain, which are called "sickle cell crises." In the past, SCD was considered a fatal disease, and many people with SCD died at a young age. Due to advances in medical care, people with SCD are now living longer lives; however, they often experience a deterioration in quality of life due to progressive organ failure. Past research has suggested that children with SCD commonly have frontal lobe dysfunction syndrome, which is a brain disorder that can affect cognitive functioning in areas such as attention, concentration, information processing, and decision making. Often times, however, neurocognitive and brain disorders are not diagnosed or treated in people with SCD. In preliminary brain imaging studies, at least half of adult participants with SCD had visible cognitive dysfunction, while participants without SCD rarely had visible changes in the brain. Brain dysfunction may be one of the most important and least-studied problems affecting adults with SCD.

Most people with SCD have anemia, or low levels of red blood cells, which are the cells that carry oxygen to the body's tissues, especially the brain. Research has shown that in people with anemia who do not have SCD, memory and attention problems have decreased after receiving treatment for anemia. The purpose of this study is to determine whether people with SCD who receive monthly blood transfusions to treat their anemia experience greater cognitive functioning than adults with SCD who receive usual care.

The first phase of this study was an observational study that enrolled adults with SCD and a control group of healthy adults who did not have SCD. Study procedures included questionnaires, neuropsychological testing, and MRI testing. At the end of the first phase, participants were asked if they were willing to take part in a second phase of the overall study in the future. Enrollment into the first phase ended in February 2008.

This current pilot study is the second phase of the overall study. In this study, participants will begin by completing questionnaires, a medical history review, a physical exam, a neurological exam, and a blood collection. Women will provide a urine sample for a pregnancy test. An MRI and neuropsychological testing will also occur. Participants will then be randomly assigned to receive either blood transfusions or usual care for 6 months. Participants assigned to blood transfusions will receive the transfusions every 3 to 4 weeks for 6 months. Before each transfusion, participants will undergo blood collection and a review of medical history and medication history. Participants assigned to usual care will receive a telephone call from study researchers at Months 1, 2, 4, and 5, at which time medical and medication history will be reviewed. At study visits at Months 3 and 6, these participants will also undergo a blood collection. At Month 6, all participants will complete health and quality of life questionnaires, neuropsychological testing, and an MRI.

Eligibility

Ages Eligible for Study:	21 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Completion of all components of the Phase 1 study (NCT00528801)
Wechsler Adult Intelligence Scale (WAIS) III-Performance IQ (PIQ) score less than or equal to 90
Hemoglobin less than or equal to 9.0 g/dL

People who did not complete Phase I of the study are eligible for enrollment in this study if they meet all of the following criteria:

Capable of giving informed consent for the study
Willing to undergo transfusion therapy for 6 months
African descent
Proficient/fluent in English
Hemoglobin electrophoresis confirming hemoglobin SS or SB0 (less than or equal to 15%)
WAIS III-PIQ score less than or equal to 90
Hemoglobin less than or equal to 9.0 g/dL
Mini-Mental Status Examination (MMSE) score of greater than or equal to 20
Profile of Mood States (POMS) score on the Depression-Dejection Subscale less than or equal to 40

Exclusion Criteria:

People who meet any of the following criteria are disqualified from enrollment in this study:

History of life threatening or serious transfusion complications
Lack of venous access
Current enrollment in the Arginine study (NCT00513617)
Pregnant
Refusal of transfusion
History of unexplained severe hemolytic transfusion reaction
History of serious allergic, pulmonary transfusion reaction requiring hospitalization
Positive auto-immune hemolytic anemia (direct Coombs test with IgG and complement)
Multiple (three or more) clinically significant allo-antibodies, due to common antigens (e.g., EC, Kel)
Uncommon, clinically significant antibody that results in difficulty in finding matched units (e.g., anti-JKB)
Currently taking Hydroxyurea and not on a stable dose in the 6 months before study entry
Creatinine level greater than 1.7 mg/dL
Ferritin level greater than 1,500 ng/mL or quantitative liver iron level greater than 7 mg/g dry weight and not currently on iron chelation therapy. (This is a pilot transfusion in which only 6 months of transfusion will be utilized. The likelihood of iron overload induced toxicity from the transfusions over the 6 months is very small. Furthermore, ferritin is disproportionately elevated in SCD and overestimates the iron burden. Therefore, a quantitative liver iron and/or ferritin level has been included as criteria for exclusion.)
Major infarct identified on Phase I MRI
Currently on Procrit or related drug that stimulates red blood cell production

In addition to the exclusion criteria listed above, people who did not complete Phase I (or who completed Phase I more than 1 year prior to enrollment into this study) are disqualified for enrollment in this study if they meet any of the following criteria:

Overt stroke
Previous evidence of an abnormal MRI or computed axial tomography (CT) scan other than small periventricular or watershed lesions
History of head injury that resulted in neurological symptoms or medical visit
Abnormal neurological exam with focal findings
Alcohol consumption exceeding 14 drinks/week if female or 21 drinks/week if male
Drug abuse, as defined as using non-prescribed medication
History of claustrophobia and/or presence of metallic implants such as pacemakers, surgical aneurysm clips, or known metal fragments embedded in the body
Baseline blood pressure greater than 140/90 mm Hg on two repeated measurements. A second measurement is needed only if the first is greater than 140/90 mm Hg.
History of uncontrolled hypertension
Any long-term disorder that may result in neurocognitive or brain dysfunction that is not secondary to SCD, including any of the following:
- Inflammatory arterial disorders (e.g., lupus, polyarteritis)
- History of cancer requiring chemotherapy and/or radiation
- Untreated hyperlipidemia
- Diabetes
- Ongoing active infection such as HIV, tuberculosis, or sarcoidosis
- History of long-term blood transfusion
- Long-term kidney failure/dialysis
- Long-term lung disease characterized by a need for oxygen
- Morbid obesity (i.e., weight greater than 115 kg)
- Heart disease, including a history of congestive heart failure, history of severe coronary artery disease characterized by angioplasty or surgery, or history of angina
- Active hepatitis or liver failure
- Acquired or congenital immune deficiency
- History of psychoses (e.g., delusions, hallucinations) and/or schizophrenia
- Neurodegenerative disorder
- Genetic disorder associated with neurocognitive dysfunction such as Down Syndrome
- Other long-term illness or disorder other than SCD that will adversely affect the person's performance in the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00850018

Locations

United States, California
Children's Hospital & Research Center at Oakland
Oakland, California, United States, 94609
United States, District of Columbia
Howard University
Washington, District of Columbia, United States, 20001
United States, Florida
Memorial Cancer Institute
Hollywood, Florida, United States, 33021
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 94117
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Karmanos Cancer Institute at Wayne State University
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27514
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229-3039
University of Cincinnati Medical Center
Cincinnati, Ohio, United States, 45267
United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

Elliott Vichinsky, MD

Children's Hospital & Research Center Oakland

More Information

No publications provided

Responsible Party:	Elliott Vichinsky, MD, Children's Hospital of Oakland and Research Institute
ClinicalTrials.gov Identifier:	NCT00850018 History of Changes
Other Study ID Numbers:	633, 2 U54 HL070587
Study First Received:	February 20, 2009
Last Updated:	December 17, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Sickle Cell Disease
Sickle Cell Anemia
Hemoglobin SS
Hemoglobin SB0

Additional relevant MeSH terms:

Congenital Abnormalities
Anemia
Anemia, Sickle Cell
Hematologic Diseases

Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on May 24, 2012