Transcranial Doppler (TCD) Ultrasound of Subjects Enrolled in BABY HUG - Ancillary to BABY HUG
Condition: Blood Disease; Anemia, Sickle Cell; Cerebrovascular Disorders; Cerebral Embolism and Thrombosis
MeSH terms: Cerebrovascular Disorders; Intracranial Embolism; Intracranial Embolism and Thrombosis; Thrombosis; Embolism; Embolism and Thrombosis; Anemia, Sickle Cell; Hematologic Diseases
Study type: Observational

Summary: 
      To use transcranial Doppler (TCD) ultrasound to detect stroke risk in children with sickle
      cell disease.
    

Detailed description: 
      BACKGROUND:

      Cerebral vasculopathy and stroke are among the most serious complications of sickle cell
      disease. Not every patient will develop central nervous system disease but most children have
      some evidence of cognitive impairment and about 10% will have overt stroke if this is not
      forestalled by transcranial Doppler (TCD) screening, identification of individuals at
      greatest risk by estimating maximal cerebral blood flow and commencing prophylactic
      transfusion. The basis of these recommendations is studies in children over age 2-years where
      stroke is most prevalent. Transfusion is not without its own serious and considerable risks
      so that other measures for delaying or preventing cerebral vasculopathy would be valuable.
      Hydroxyurea (HU) can reduce both morbidity and mortality of sickle cell anemia in adults;
      most likely the same pertains in children. Unknown are the effects of HU in infants and the
      youngest children and whether its successful use can reduce the risks of sickle
      cerebrovascular disease. If HU is associated with reduced TCD velocity, and if it is safe in
      infants, the medical implications would be high.

      Baby TCD is an ancillary study to the initial phase of BABY HUG, a multicenter clinical trial
      funded by the NHLBI. In BABY HUG, infants (12-17 months old) with sickle cell disease (SCD)
      will be randomized to either hydroxyurea (HU) or placebo and followed for 24 months. There is
      broad interest in the effect of hydroxyurea on the central nervous system in the children
      being studied. Stroke occurs after age 1 year and there is evidence that the process of
      cerebrovascular disease starts very early in some patients. The Cooperative Study of Sickle
      Cell Disease documented a high risk of incident stroke in the 2-6 year age group. The study
      is in response to an initiative on Ancillary Studies in Heart, Lung, and Blood Disease Trials
      released in June, 2000.

      DESIGN NARRATIVE:

      The study will perform TCD on the 40 children in BABY HUG at baseline and at the end of
      study. TCD has proven very useful in estimation of stroke risk in children with SCD ages 2-16
      years, and is at the center of a paradigm of primary stroke prevention recommended by the
      National Heart, Lung, and Blood Institute based on the STOP study. If stroke risk could be
      detected at an earlier stage (i.e., younger than the 2-16 year-old subjects in STOP), then
      physicians would be able to provide preventive treatment at an earlier stage of the disease.
      TCD will be performed before and after 24 months of treatment. TCD performance and reading
      will be centrally controlled and STOP-consistent. The investigators have experience in TCD of
      infants, the age targeted by the parent study. TCD will be compared between HU and control
      groups, before and after treatment. In addition, the investigators have access to data from
      over 400 children in the 2-4 year age range from the STOP screening program performed in the
      mid- to late 1990s. Since these patients were not on HU or transfusion this dataset will be
      used to give an estimate of the prevalence of high stroke risk without HU treatment, and can
      be compared to the HU group in Baby HUG, adding another important comparative dimension to
      the analyses. Although the sample size is purposely small as designed by the parent study,
      large differences in the prevalence of high-risk patients at the end of treatment could be
      detected by Baby TCD.
    

Study population: 
        The BABY HUG Follow-up Study I was an observational study to provide structured monitoring
        of the subjects enrolled in the BABY HUG Treatment Study, to initiate characterization of
        the long-term toxicities and unexpected risks (if any) associated with treatment with
        hydroxyurea at an early age, and any potential benefits of therapy.