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Examining Cognitive Function and Brain Abnormalities in Adults With Sickle Cell Disease
This study has been completed.

First Received on September 10, 2007.   Last Updated on May 12, 2010   History of Changes
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Information provided by: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00528801
  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 and adults without SCD.

212 subjects participated in this cross-sectional study consisting of screening questionnaires, a neuropsychological testing battery, and MRI testing. Enrollment into this study ended in May 2008.


Condition Intervention
Anemia, Sickle Cell
 Behavioral: NP Battery
Procedure: MRI

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Neuropsychological Dysfunction and Neuroimaging Abnormalities in Neurologically Intact Adults With Sickle Cell Disease

Resource links provided by NLM:

Genetics Home Reference related topics: sickle cell disease
MedlinePlus related topics: Anemia Memory Sickle Cell Anemia
U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Wechsler Adult Intelligence Scale (WAIS)-III Performance IQ [ Time Frame: Within 2 months of signing informed consent. ] [ Designated as safety issue: No ]
    Extent of neurocognitive dysfunction in neurologically asymptomatic adult patients with sickle cell disease as measured by WAIS-III performance IQ. This quotient is based on an average of 100, with a standard deviation of 15. The Wechsler intelligence scales are not considered adequate measures of extremely high and low intelligence (IQ scores above 160 and below 40, respectively). The performance IQ is derived from scores on seven subtests: picture completion, picture arrangement, block design, object assembly, digit symbol, matrix reasoning, and symbol search.


Secondary Outcome Measures:
  • Participants With Brain Lacunae as Measured by Clinical MRI [ Time Frame: Within 2 months of informed consent ] [ Designated as safety issue: No ]
    Particpants with imaging abnormalities as measured by MRI (Magnetic Resonance Imaging) specifically brain lacunae. Lacunar infarcts are 3-15 mm in diameter located at the basal ganglia, capsular and thalamic regions. Lesions located at the level of the anterior commisure are considered perivascular spaces unless >5 mm in diameter.

  • Volume of Total Cortical Gray Matter as Measured by Volumetric MRI. [ Time Frame: Within 2 months of informed consent ] [ Designated as safety issue: No ]
    The cortical gray matter is the gray matter of the cerebral cortex only and does not include subcortical gray matter such as hippocampus or basal ganglia.


Enrollment: 212
Study Start Date: December 2004
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Cases (CLOSED)
These are patients diagnosed with sickle cell disease (confirmed by hemoglobin electrophoresis).
 Behavioral: NP Battery
Neuropsych Battery with 7 different tests that evaluate the patients neurological functioning.
Other Names:
  • The Weschler Adult Intelligence Scale - Third Edition
  • The Woodcock Johnson Revised - Test of Achievement
  • The Delis-Kaplan Function System
  • The Wisconsin Card Sorting test
  • The Test of Everday Attention
  • The California Verbal Learning Test
  • The Weschler Memory Scales - Third Edition
Procedure: MRI
The MRI is a standard procedure involving 30 minutes under the machine in order to obtain various images of the patients brain.
Controls (CLOSED)
These are persons that do not have sickle cell disease (confirmed by hemoglobin electrophoresis); matched to cases by age, gender, and education level
 Behavioral: NP Battery
Neuropsych Battery with 7 different tests that evaluate the patients neurological functioning.
Other Names:
  • The Weschler Adult Intelligence Scale - Third Edition
  • The Woodcock Johnson Revised - Test of Achievement
  • The Delis-Kaplan Function System
  • The Wisconsin Card Sorting test
  • The Test of Everday Attention
  • The California Verbal Learning Test
  • The Weschler Memory Scales - Third Edition
Procedure: MRI
The MRI is a standard procedure involving 30 minutes under the machine in order to obtain various images of the patients brain.

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 cognitive dysfunction that could be seen in images of the brain, 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. The purpose of this study is to evaluate the extent of cognitive functioning problems in adults with SCD. The study will also determine if there is a connection between cognitive functioning problems and abnormalities seen on MRI brain images of adults with SCD.

This study is an observational case/control study that will enroll adults with SCD and a control group of healthy adults who do not have SCD. At a study visit on Day 1, participants will undergo blood collection and will complete psychosocial questionnaires. Female participants will provide a urine sample for pregnancy testing. Study researchers will conduct a medical record review, a physical exam, and a neurological exam. They will also interview participants to collect medical history information. On Day 2, participants will undergo either a brain MRI or neuropsychological testing; on Day 3, the other procedure will be completed. On Day 4, study researchers will explain the study procedure results to participants. Participants will be asked if they are willing to take part in a second phase of the study in the future. Enrollment into this study ended in May 2008.

A pilot interventional study follows this study, and is reported separately in ClinicalTrials.gov under NCT 00850018.

  Eligibility

Ages Eligible for Study:   21 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

212 participants, 160 will have sickle cell anemia, 52 will be matched controls based on gender, age, and education level

Criteria

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as cases into the study:

  1. Adult between the ages of 21 and 55
  2. African descent
  3. Proficient/fluent in English
  4. Hemoglobin electrophoresis confirming hemoglobin SS or SB0 (%A <= 15)
  5. Hemoglobin <= 10 g/dL
  6. Capable of giving informed consent for the protocol

Individuals who meet all of the following criteria are eligible for enrollment as community controls into the study:

  1. Adult between the ages of 21 and 55
  2. African descent
  3. Proficient/fluent in English
  4. Capable of giving informed consent for the protocol

Exclusion Criteria:

Individuals who meet any of the following criteria are disqualified from enrollment in the case group of the study:

  1. Overt stroke
  2. Previous evidence of an abnormal MRI or CT other than small peri-ventricular or watershed lesions
  3. History of head injury that resulted in neurological symptoms or medical visit
  4. Abnormal neurologic exam with focal findings
  5. Mini-Mental Status Examination (MMSE) score of < 20
  6. Profile of Mood States (POMS) score on the Depression-Dejection Subscale suggestive of a clinical depression (score > 40)
  7. Alcohol consumption exceeding 14 drinks/week if female, 21 drinks/week if male
  8. Drug abuse, defined as using non-prescribed medication
  9. History of claustrophobia and/or presence of metallic implants such as pacemakers, surgical aneurysm clips, or known metal fragments embedded in the body
  10. Pregnancy
  11. Baseline blood pressure > 140/90 on two repeated measurements. A second measurement is needed only if the first is > 140/90
  12. History of uncontrolled hypertension

  13. Any chronic disorder that may result in neurocognitive or brain dysfunction that is not secondary to SCD including:

    1. Inflammatory arterial disorders (lupus, polyarteritis)
    2. History of cancer requiring chemotherapy and/or radiation
    3. Untreated hyperlipidemia
    4. Diabetes
    5. Ongoing active infection such as HIV, tuberculosis, sarcoidosis
    6. History of chronic transfusion
    7. Chronic renal failure/Dialysis
    8. Chronic lung disease characterized by need for oxygen
    9. Morbid obesity (weight >115 kg)
    10. Heart disease: history of congestive heart failure, history of severe coronary artery disease characterized by angioplasty or surgery, or history of angina
    11. Active hepatitis or liver failure
    12. Acquired or congenital immune deficiency
    13. History of psychoses (delusions, hallucinations) and/or schizophrenia
    14. Neurodegenerative disorders
    15. Genetic disorder associated with neurocognitive dysfunction such as Down Syndrome
    16. Other chronic illness or disorder other than SCD that will adversely affect the subject's performance in the study
  14. Currently on Procrit or related drug that stimulates red blood cell production

Individuals who meet any of the following criteria are disqualified from enrollment as community controls in to the study:

  1. Hb electrophoresis other than AA
  2. Abnormal Hb (females: < 12 g/dL; males: < 13.5 g/dL)
  3. Overt stroke
  4. Previous abnormal MRI or CT
  5. History of head injury that resulted in neurological symptoms or medical visit
  6. Abnormal neurologic exam with focal findings
  7. Mini-Mental Status Examination (MMSE) score of < 20
  8. Profile of Mood States (POMS) score on the Depression-Dejection Subscale suggestive of a clinical depression (score > 40)
  9. Alcohol consumption exceeding 14 drinks/week if female, 21 drinks/week if male
  10. Drug abuse, defined as using non-prescribed medication
  11. History of claustrophobia and/or presence of metallic implants such as pacemakers, surgical aneurysm clips, or known metal fragments embedded in the body
  12. Pregnancy
  13. Baseline blood pressure > 140/90 on two repeated measurements. A second measurement is needed only if the first is > 140/90
  14. History of uncontrolled hypertension

  15. Any chronic disorder that may result in neurocognitive or brain dysfunction including:

    1. Inflammatory arterial disorders (lupus, polyarteritis)
    2. History of cancer requiring chemotherapy and/or radiation
    3. Untreated hyperlipidemia
    4. Diabetes
    5. Ongoing active infection such as HIV, tuberculosis, sarcoidosis
    6. History of chronic transfusion
    7. Chronic renal failure/Dialysis
    8. Chronic lung disease characterized by need for oxygen
    9. Morbid obesity (weight > 115 kg)
    10. Heart disease: history of congestive heart failure, history of severe coronary artery disease characterized by angioplasty or surgery, or history of angina
    11. Active hepatitis or liver failure
    12. Acquired or congenital immune deficiency
    13. History of psychoses (delusions, hallucinations) and/or schizophrenia
    14. Neurodegenerative disorders
    15. Genetic disorder associated with neurocognitive dysfunction such as Down Syndrome
    16. Other chronic illness or disorder that will adversely affect the subject's performance in the study
  16. Currently on Procrit or related drug that stimulates red blood cell production
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00528801

Locations
United States, California
University of Southern California
Los Angeles, California, United States, 90033
Children's Hospital & Research Center at Oakland
Oakland, California, United States, 94609
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, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
University of Cincinnati Medical Center
Cincinnati, Ohio, United States, 45267
United States, Texas
Children's Medical Center at Dallas
Dallas, Texas, United States, 75390
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 Northern California CSCC (Children's Hospital Oakland)
  More Information

No publications provided

Responsible Party: Elliott Vichinsky, Children's Hospital of Oakland and Research Institute
ClinicalTrials.gov Identifier: NCT00528801     History of Changes
Other Study ID Numbers: 480, U54 HL070587-04
Study First Received: September 10, 2007
Results First Received: August 28, 2009
Last Updated: May 12, 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 February 09, 2012



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