Blood Flow and Pain Crises in People With Sickle Cell Disease
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Study type: Observational

Summary: 
      Background:

      - Many people with sickle cell disease have repeated episodes of severe pain that lasts for
      days, requiring hospital care. These episodes, called pain crises, may be caused by changes
      in blood flow. Researchers want to study blood flow in people with sickle cell disease who
      are having a pain crisis and compare it with their blood flow after the pain crisis has
      resolved. They also want to compare these measurements against blood flow in healthy people
      who do not have sickle cell disease.

      Objectives:

      - To study whether changes in blood flow cause pain crises in people with sickle cell
      disease.

      Eligibility:

        -  Individuals at least 18 years of age who have sickle cell disease and are being treated
           for a pain crisis.

        -  Individuals at least 18 years of age who have sickle cell disease and are not
           experiencing a pain crisis.

        -  Healthy volunteers matched by age and gender with the participants who have sickle cell
           disease.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected.

        -  Participants having a sickle cell pain crisis will have two visits, one during the
           crisis and one about 4 weeks after the crisis has resolved.

        -  Participants not having a sickle cell pain crisis will have one or two study visits.
           Blood samples will be collected during at least one of these visits.

        -  Healthy volunteers will have one or two study visits. Blood samples will be collected
           during at least one of these visits.

        -  During each visit for all participants, cameras and blood flow monitoring equipment will
           be used to measure blood flow in the forearm.

      sickle cell disease.
    

Detailed description: 
      Severe recurrent pain is the most common cause of acute morbidity in sickle cell disease1.
      The underlying pathogenesis was initially thought to be ischemia from obstruction of
      capillary beds by stiffened red blood cells; however, there is evidence that other factors
      contribute to the pathogenesis of sickle cell pain crisis, such as inflammation and
      coagulation, ischemia-reperfusion injury, angiogenesis balance, and vasomotor tone processes
      that are regulated by endothelial nitric oxide.

      Recent clinical data suggest that subjects with sickle cell disease suffer from chronically
      impaired nitric oxide bioavailability. This has been attributed to increased consumption of
      nitric oxide by hemoglobin and reactive oxygen species, or decreased production of nitric
      oxide by endothelial cells; however the roles of nitric oxide bioavailability and endothelial
      dysfunction during acute pain crisis are controversial and incompletely understood. Although
      there have been several studies of endothelial function in steady state sickle cell disease,
      there has been no comprehensive study of endothelial function during pain crisis.

      In this study, our primary objective is to measure the reactive hyperemia index (a measure of
      the endothelial response to shear stress) in twenty sickle cell subjects during acute pain
      crisis and to compare it with the reactive hyperemia index measured after recovery from pain
      crisis. This will identify whether there are acute changes in endothelial cell function
      during sickle cell pain crisis. Our secondary objective is to compare the reactive hyperemia
      index of thirty-five sickle cell subjects in steady state versus the reactive hyperemia index
      of thirty-five healthy control subjects. This will identify whether there are chronic
      differences in endothelial function between sickle cell subjects and healthy control
      subjects.

      This study will determine if there are defects in endothelium-dependent vasodilation in
      response to shear stress during sickle cell pain crisis. Moreover, this study provides an
      opportunity to evaluate new physiologic biomarkers of sickle cell pain crisis based on
      measurements of blood flow, temperature, and oxygenation in the skin. These measurements may
      serve as clinical endpoints in future studies of disease pathogenesis or therapeutic
      interventions for sickle cell disease.
    

Time perspective: Prospective
Keywords: Blood Flow; Endothelium; Nitric Oxide; Oximetry; Laser Doppler; Sickle Cell Disease