Anemia, Sickle CellPhase 1NCT00850018
Examining Cognitive Function and Brain Abnormalities in Adults With Sickle Cell Disease - Pilot Intervention Study
A Phase 1 study testing Monthly blood transfusion regimen in people with Anemia, Sickle Cell, run by UCSF Benioff Children's Hospital Oakland at 14 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?
- Monthly blood transfusion regimen
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 14 sitesUnited States
- Study dates
- Dec 2004to Dec 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Medical College of Georgia
Augusta, Georgia, 30912
Johns Hopkins
Baltimore, Maryland, 94117
Boston Medical Center
Boston, Massachusetts, 02118
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229-3039
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267
Karmanos Cancer Institute at Wayne State University
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27710
University of Texas Medical Branch
Galveston, Texas, 77555
Memorial Cancer Institute
Hollywood, Florida, 33021
University of Miami Miller School of Medicine
Miami, Florida, 33136
Children's Hospital & Research Center at Oakland
Oakland, California, 94609
Washington University
St Louis, Missouri, 63110
Howard University
Washington D.C., District of Columbia, 20001
About this study
Official title: Neuropsychological Dysfunction and Neuroimaging Abnormalities in Neurologically Intact Adults With Sickle Cell Disease - A Pilot Intervention Study
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.
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 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.
- Conditions
- Anemia, Sickle Cell
- Being tested
- Monthly blood transfusion regimen, Usual care
- 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.
Monthly blood transfusion regimenProcedure or surgery
Also called Chronic transfusion therapy
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.
Usual careBehavioural
Also called Standard care alone, guided by disease symptoms.
Participants will receive usual care for the treatment of SCD.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive monthly blood transfusions. Receives: Procedure: Monthly blood transfusion regimen |
| 2 | Active comparator | Participants will receive usual care. Receives: Behavioral: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive function
Measured: Measured at Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2009 (estimated)
- Study startDec 2004
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
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, UCSF Benioff Children's Hospital Oakland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00850018
- Sponsor's protocol ID
- 633
- Other IDs
- U54HL070587, 2U54HL070587
- Status last verified
- Feb 2017
- First submitted
- 20 Feb 2009
- Last updated
- 15 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 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 - A Pilot Intervention Study
- ClinicalTrials.gov ID
- NCT00850018
- Acronym / sponsor ID
- 633
- Conditions
- Anemia, Sickle Cell
- Keywords
- Sickle Cell Disease, Sickle Cell Anemia, Hemoglobin SS, Hemoglobin SB0
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (estimated)
- 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
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 24 Feb 2009 (estimated)
- Results
- Not posted in the source record
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 who are treated for anemia with monthly blood transfusions for 6 months versus adults with SCD who receive usual care for 6 months.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Procedure: Monthly blood transfusion regimenParticipants will receive monthly blood transfusions. |
| 2 | Active comparator | Behavioral: Usual careParticipants will receive usual care. |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (43 listed)
- 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
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 |
|---|---|---|
| Monthly blood transfusion regimenAlso: Chronic transfusion therapyParticipants 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. | Procedure or surgery | 1 |
| Usual careAlso: Standard care alone, guided by disease symptoms.Participants will receive usual care for the treatment of SCD. | Behavioural | 2 |
Primary outcome
Cognitive function
Time frame: Measured at Month 6
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2017.
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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
UCSF Benioff Children's Hospital Oakland
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Monthly blood transfusion regimen in people with Anemia, Sickle Cell, run by UCSF Benioff Children's Hospital Oakland at 14 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 13 inclusion and 43 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 15 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cognitive function (time frame: Measured at Month 6). 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 15 Feb 2017.