Clinical trial NCT00528801: Examining Cognitive Function and Brain Abnormalities in Adults With Sickle Cell Disease
Official title: Neuropsychological Dysfunction and Neuroimaging Abnormalities in Neurologically Intact Adults With Sickle Cell Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Anemia, Sickle Cell
Keywords: Sickle Cell Disease
Sickle Cell Anemia
Hemoglobin SS
Hemoglobin SB0
Lead sponsor: UCSF Benioff Children's Hospital Oakland
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2007-09-12
Enrollment: 212
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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

Brief summary: 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.

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 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

Primary outcomes:
measure: Wechsler Adult Intelligence Scale (WAIS)-III Performance IQ
timeFrame: Within 2 months of signing informed consent.
Secondary outcomes:
measure: Participants With Brain Lacunae as Measured by Clinical MRI
timeFrame: Within 2 months of informed consent
measure: Volume of Total Cortical Gray Matter as Measured by Volumetric MRI.
timeFrame: Within 2 months of informed consent
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Oakland
country: United States
facility: Children's Hospital & Research Center at Oakland
state: California
city: Hollywood
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Dallas
country: United States
facility: Children's Medical Center at Dallas
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
Study officials:
affiliation: Northern California CSCC (Children's Hospital Oakland)
name: Elliott Vichinsky, MD
role: PRINCIPAL_INVESTIGATOR
References: