Microvascular Blood Flow in Sickle Cell Anemia

Sickle cell disease (SCD) is an inherited blood disorder that causes the red blood cells to change their shape from a round shape to a half-moon/crescent or sickled shape. Sickle-shaped cells can cause problems by getting stuck in blood vessels, blocking blood flow, and can cause inflammation and injury to important body parts. There are no specific treatments that improve this condition and promote blood flow hindered by sickle cell blockages. Another big challenge in managing sickle cell disease is that there are no good measures to determine changes and improvements in blood flow.

Contrast-enhanced ultrasound is a technique currently used to detect blood flow in the heart, muscles, and other organs. It is extremely sensitive and can detect blood flow in the smallest of blood vessels. It would be very useful in helping healthcare providers know whether treatment strategies are improving blood flow during sickle cell blockages.

The hypothesis is that contrast-enhanced ultrasound will be a feasible tool for determining changes in blood flow of subjects with sickle cell disease.

Sickle cell disease is an inherited blood disorder that affects one of every 400 African-Americans newborns in the United States. Sickle cell disease causes the red blood cells to change their shape from a round shape to a half-moon sickle shape. Individuals who have sickle cell disease have a different type of protein that carries oxygen in the blood (hemoglobin) than individuals without sickle cell disease. This different type of hemoglobin makes the red blood cell change into a crescent shape under certain conditions. Sickle shaped cells are a problem because the often get stuck on blood vessels blocking the flow of blood, and cause inflammation and injury to important areas of the body. These symptoms can lead to a painful occurrence called a "sickle cell crisis". Many individuals have to be admitted into the hospital because of the pain caused by a sickle cell crisis.

Regadenoson is a drug that may help prevent inflammation and injury caused by the sickle shaped cells. This drug is approved by the FDA to be used as a bolus during a heart stress test in people unable to exercise enough to put stress on the heart by making it beat faster. In a recent Phase I study, a safe dose for regadenoson was determined for adults with sickle cell disease. This dose was given by a slow IV infusion for a 24-48 hour period.

Hydroxyurea is the only FDA approved drug for the treatment of sickle cell disease. Hydroxyurea is a pill taken orally and works well but is not useful during a severe sickle cell crisis.

In this study researchers will use a new method, contrast-enhanced ultrasound (CEU), to visualize tiny blood vessels in cardiac and skeletal muscle. Changes in CEU measurements before, during and after administration of regadenoson will be examined. Contrast-enhanced ultrasounds will also be performed in individuals who are not having a sickle cell crisis. Some of those individuals will also undergo CEU while they are having a sickle cell crisis to compare those measurements . Lastly CEU results will be compared between individuals with sickle cell anemia and healthy African-Americans. These CEU's will be used to determine if there are changes in the blood flow of tiny blood vessels in certain conditions.

This study wants to know if this new method of contrast-enhanced ultrasound will be a useful tool for physicians to use in individuals with sickle cell anemia. The researchers also want to determine if this new method of CEU can be used to reveal if some treatments for sickle cell anemia work better than others.

Eligibility Criteria:
Inclusion Criteria:

Regadenoson ARM Inclusion Criteria:

* Diagnosis of sickle cell anemia confirmed by hemoglobin analysis
* Ages 18 to 70 years
* Subjects must have laboratory indices as outlined by the protocol
* Reliable IV access as determined by physician

Sickle Cell Controls ARM Inclusion Criteria:

* Diagnosis of sickle cell anemia confirmed by hemoglobin analysis
* Ages 18 to 70 years

Sickle Cell CEU ARM Inclusion Criteria:

* Diagnosis of sickle cell anemia, confirmed by hemoglobin analysis
* Males and females age 18-70 years

Healthy Control ARM Inclusion Criteria:

* African American
* Ages 18 to 70 years

Technique Optimization Control ARM Inclusion Criteria:

-Ages 18 to 70 years

Exclusion Criteria:

Regadenoson ARM Exclusion Criteria

* Hospitalization, emergency department visit or self-reported crisis within last 2 weeks for any reason or 4 weeks from acute chest syndrome
* Current physician diagnosis of active asthma (within last 12 months) or current use of asthma medications
* Second or third degree AV block or sinus node dysfunction
* Known or suspected right to left sided cardiac shunts
* History of a bleeding diathesis
* History of clinically overt stroke
* History of severe hypertension not adequately controlled with anti-hypertensive medications
* Receiving chronic anti-coagulation or anti-platelet therapy
* History of metastatic cancer
* Receiving other investigational study agents, or have received a study agent in the last 30 days
* Uncontrolled intercurrent illness
* Pregnant or breastfeeding women
* Subjects who have a HIV infection
* Subjects who have had a hematopoietic stem cell transplant
* Subjects who are taking medications that may interact with the investigational agent
* Prior hypersensitivity reactions to either regadenoson or ultrasound contrast agents

Sickle Cell Controls Exclusion Criteria:

* Hospitalization, emergency department visit or self-reported crisis within last 2 weeks for any reason or 4 weeks from acute chest syndrome
* Known pregnancy
* Known history of HIV
* Known or suspected right to left sided cardiac shunts
* Receiving other investigational study agents, or have received a study agent within the last 30 days
* Subjects who have had a hematopoietic stem cell transplant
* Prior hypersensitivity reactions to ultrasound contrast agents
* History of severe hypertension not adequately controlled with anti-hypertensive medications
* Uncontrolled intercurrent illness

Sickle Cell CEU ARM Exclusion Criteria:

* Pregnant women
* Subjects who have a HIV infection
* History of stem cell transplant
* Current involvement in a therapeutic clinical trial
* Known or suspected right to left sided cardiac shunts
* Prior hypersensitivity reactions to ultrasound contrast agents
* History of severe hypertension not adequately controlled with anti-hypertensive medications
* Uncontrolled intercurrent illness

Healthy Control ARM Exclusion Criteria:

* Sickle cell disease or sickle cell trait
* Known or suspected right to left sided cardiac shunts
* Diagnosis of type 1 or type 2 diabetes mellitus
* Hypertension
* History or current diagnosis of dyslipidemia or taking lipid lowering drugs
* Diagnosis of coronary artery disease or peripheral vascular disease
* Body weight greater than 10% of ideal weight
* Uncontrolled intercurrent illness
* Pregnant or breastfeeding women
* Subjects who have a HIV infection
* Prior hypersensitivity reactions to ultrasound contrast agents

Technique Optimization Control ARM Exclusion Criteria:

* Known sickle cell disease or sickle cell trait
* Known or suspected right to left sided cardiac shunts
* Uncontrolled intercurrent illness
* Known pregnant or breastfeeding women
* Prior hypersensitivity reactions to ultrasound contrast agents