Anemia, Sickle CellNCT00528801
Examining Cognitive Function and Brain Abnormalities in Adults With Sickle Cell Disease
An observational study of Anemia, Sickle Cell, run by UCSF Benioff Children's Hospital Oakland at 12 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Anemia, Sickle Cell
- What is being tested?
- NP Battery and MRI
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- How many people
- 212 participants
- Where
- 12 sitesUnited States
- Study dates
- Dec 2004to May 2008
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: 212 participants, 160 will have sickle cell anemia, 52 will be matched controls based on gender, age, and education level
Who may be able to join
- Individuals who meet all of the following criteria are eligible for enrollment as cases into the study:
- Adult between the ages of 21 and 55
- African descent
- Proficient/fluent in English
- Hemoglobin electrophoresis confirming hemoglobin SS or SB0 (%A <= 15)
- Hemoglobin <= 10 g/dL
Show all 12Show fewer
- 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:
- Adult between the ages of 21 and 55
- African descent
- Proficient/fluent in English
- Capable of giving informed consent for the protocol
Who cannot join
- Individuals who meet any of the following criteria are disqualified from enrollment in the case group of the study:
- Overt stroke
- Previous evidence of an abnormal MRI or CT other than small peri-ventricular or watershed lesions
- History of head injury that resulted in neurological symptoms or medical visit
- Abnormal neurologic exam with focal findings
- Mini-Mental Status Examination (MMSE) score of < 20
Show all 64Show fewer
- Profile of Mood States (POMS) score on the Depression-Dejection Subscale suggestive of a clinical depression (score > 40)
- Alcohol consumption exceeding 14 drinks/week if female, 21 drinks/week if male
- Drug abuse, 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
- Pregnancy
- Baseline blood pressure > 140/90 on two repeated measurements. A second measurement is needed only if the first is > 140/90
- History of uncontrolled hypertension
- Any chronic disorder that may result in neurocognitive or brain dysfunction that is not secondary to SCD including:
- Inflammatory arterial disorders (lupus, polyarteritis)
- History of cancer requiring chemotherapy and/or radiation
- Untreated hyperlipidemia
- Diabetes
- Ongoing active infection such as HIV, tuberculosis, sarcoidosis
- History of chronic transfusion
- Chronic renal failure/Dialysis
- Chronic lung disease characterized by need for oxygen
- Morbid obesity (weight >115 kg)
- Heart disease: 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 (delusions, hallucinations) and/or schizophrenia
- Neurodegenerative disorders
- Genetic disorder associated with neurocognitive dysfunction such as Down Syndrome
- Other chronic illness or disorder other than SCD that will adversely affect the subject's performance in the study
- 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:
- Hb electrophoresis other than AA
- Abnormal Hb (females: < 12 g/dL; males: < 13.5 g/dL)
- Overt stroke
- Previous abnormal MRI or CT
- History of head injury that resulted in neurological symptoms or medical visit
- Abnormal neurologic exam with focal findings
- Mini-Mental Status Examination (MMSE) score of < 20
- Profile of Mood States (POMS) score on the Depression-Dejection Subscale suggestive of a clinical depression (score > 40)
- Alcohol consumption exceeding 14 drinks/week if female, 21 drinks/week if male
- Drug abuse, 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
- Pregnancy
- Baseline blood pressure > 140/90 on two repeated measurements. A second measurement is needed only if the first is > 140/90
- History of uncontrolled hypertension
- Any chronic disorder that may result in neurocognitive or brain dysfunction including:
- Inflammatory arterial disorders (lupus, polyarteritis)
- History of cancer requiring chemotherapy and/or radiation
- Untreated hyperlipidemia
- Diabetes
- Ongoing active infection such as HIV, tuberculosis, sarcoidosis
- History of chronic transfusion
- Chronic renal failure/Dialysis
- Chronic lung disease characterized by need for oxygen
- Morbid obesity (weight > 115 kg)
- Heart disease: 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 (delusions, hallucinations) and/or schizophrenia
- Neurodegenerative disorders
- Genetic disorder associated with neurocognitive dysfunction such as Down Syndrome
- Other chronic illness or disorder that will adversely affect the subject's performance in the study
- Currently on Procrit or related drug that stimulates red blood cell production
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Medical College of Georgia
Augusta, Georgia, 30912
Boston Medical Center
Boston, Massachusetts, 02118
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267
Children's Medical Center at Dallas
Dallas, Texas, 75390
Duke University Medical Center
Durham, North Carolina, 27705
University of Texas Medical Branch
Galveston, Texas, 77555
Memorial Cancer Institute
Hollywood, Florida, 33021
University of Southern California
Los Angeles, California, 90033
University of Miami Miller School of Medicine
Miami, Florida, 33136
Children's Hospital & Research Center at Oakland
Oakland, California, 94609
About this study
Official title: Neuropsychological Dysfunction and Neuroimaging Abnormalities in Neurologically Intact Adults With Sickle Cell Disease
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.
Read the 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.
- Conditions
- Anemia, Sickle Cell
- Being tested
- NP Battery, MRI
- Keywords
- Sickle Cell Disease, Sickle Cell Anemia, Hemoglobin SS, Hemoglobin SB0
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NP BatteryBehavioural
Also called The Weschler Adult Intelligence Scale - Third Edition, The Woodcock Johnson Revised - Test of Achievement, The Delis-Kaplan Function System, The Wisconsin Card Sorting test
Neuropsych Battery with 7 different tests that evaluate the patients neurological functioning.
MRIProcedure or surgery
The MRI is a standard procedure involving 30 minutes under the machine in order to obtain various images of the patients brain.
| Study group | Role | What they receive |
|---|---|---|
| Cases (CLOSED) | These are patients diagnosed with sickle cell disease (confirmed by hemoglobin electrophoresis). Receives: Behavioral: NP Battery; Procedure: MRI | |
| 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 Receives: Behavioral: NP Battery; Procedure: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wechsler Adult Intelligence Scale (WAIS)-III Performance IQ
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.
Measured: Within 2 months of signing informed consent.
Secondary outcomes (2)
Participants With Brain Lacunae as Measured by Clinical MRI
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.
Measured: Within 2 months of informed consent
Volume of Total Cortical Gray Matter as Measured by Volumetric MRI.
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.
Measured: Within 2 months of informed consent
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2007 (estimated)
- Study startDec 2004
- Primary completionMay 2008
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Anemia, Sickle CellStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 212 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCSF Benioff Children's Hospital Oakland
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Investigators
- Elliott Vichinsky, MD, Principal investigator, Northern California CSCC (Children's Hospital Oakland)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00528801
- Sponsor's protocol ID
- 480
- Other IDs
- U54HL070587, U54HL070587-04
- Status last verified
- Feb 2017
- First submitted
- 10 Sep 2007
- Last updated
- 21 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuropsychological Dysfunction and Neuroimaging Abnormalities in Neurologically Intact Adults With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT00528801
- Acronym / sponsor ID
- 480
- Conditions
- Anemia, Sickle Cell
- Keywords
- Sickle Cell Disease, Sickle Cell Anemia, Hemoglobin SS, Hemoglobin SB0
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 212 participants (actual)
- Lead sponsor
- UCSF Benioff Children's Hospital OaklandUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Dec 2004
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 12 Sep 2007 (estimated)
- Results
- Posted 26 Nov 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cases (CLOSED) | – | Behavioral: NP Battery, Procedure: MRIThese are patients diagnosed with sickle cell disease (confirmed by hemoglobin electrophoresis). |
| Controls (CLOSED) | – | Behavioral: NP Battery, Procedure: MRIThese are persons that do not have sickle cell disease (confirmed by hemoglobin electrophoresis); matched to cases by age, gender, and education level |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- 212 participants, 160 will have sickle cell anemia, 52 will be matched controls based on gender, age, and education level
Key inclusion criteria (12 listed)
- Individuals who meet all of the following criteria are eligible for enrollment as cases into the study:
- Adult between the ages of 21 and 55
- African descent
- Proficient/fluent in English
- Hemoglobin electrophoresis confirming hemoglobin SS or SB0 (%A <= 15)
Key exclusion criteria (64 listed)
- Individuals who meet any of the following criteria are disqualified from enrollment in the case group of the study:
- Overt stroke
- Previous evidence of an abnormal MRI or CT other than small peri-ventricular or watershed lesions
- History of head injury that resulted in neurological symptoms or medical visit
- Abnormal neurologic exam with focal findings
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NP BatteryAlso: The Weschler Adult Intelligence Scale - Third Edition, The Woodcock Johnson Revised - Test of Achievement, The Delis-Kaplan Function System, The Wisconsin Card Sorting testNeuropsych Battery with 7 different tests that evaluate the patients neurological functioning. | Behavioural | Cases (CLOSED), Controls (CLOSED) |
| MRIThe MRI is a standard procedure involving 30 minutes under the machine in order to obtain various images of the patients brain. | Procedure or surgery | Cases (CLOSED), Controls (CLOSED) |
Primary outcome
Wechsler Adult Intelligence Scale (WAIS)-III Performance IQ
Time frame: Within 2 months of signing informed consent.
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.
2 secondary outcomes
Participants With Brain Lacunae as Measured by Clinical MRI
Time frame: Within 2 months of informed consent
Volume of Total Cortical Gray Matter as Measured by Volumetric MRI.
Time frame: Within 2 months of informed consent
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elliott Vichinsky, MD principal investigator
Northern California CSCC (Children's Hospital Oakland)
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anemia, Sickle Cell, run by UCSF Benioff Children's Hospital Oakland at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 64 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Nov 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Wechsler Adult Intelligence Scale (WAIS)-III Performance IQ (time frame: Within 2 months of signing informed consent.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2017.