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

This is an interventional treatment trial for Anemia, Sickle Cell focused on measuring Sickle Cell Disease, Sickle Cell Anemia, Hemoglobin SS, Hemoglobin SB0 Read More

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