Microvascular Blood Flow in Sickle Cell Anemia

Not Applicable

Completed

Conditions: Sickle Cell Disease
Sickle Cell Anemia

Interventions: Procedure: contrast-enhanced ultrasound
Drug: regadenoson infusion with contrast-enhanced ultrasound

Registration Number: NCT01566890

Lead Sponsor: Versiti

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 91

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Technique Optimization Controls	contrast-enhanced ultrasound	Healthy volunteers will undergo contrast-enhanced ultrasound.
Regadenoson ARM	regadenoson infusion with contrast-enhanced ultrasound	Adult subjects with sickle cell anemia will receive a regadenoson infusion with contrast-enhanced ultrasound
Sickle Cell CEU ARM	contrast-enhanced ultrasound	Adults subjects with sickle cell anemia will receive contrast-enhanced ultrasound
Healthy Control ARM	contrast-enhanced ultrasound	Healthy African American control subjects without sickle cell anemia will receive contrast-enhanced ultrasound
Sickle Cell Controls ARM	contrast-enhanced ultrasound	Adult subjects with sickle cell anemia will receive contrast-enhanced ultrasound

Primary Outcome Measures

Name	Time	Method
Microvascular Blood Flow Rate Change	Between baseline and 24 hours	Primary outcome measure will be a 40% increase in skeletal muscle microvascular blood flow when 24 hour measurements are compared to baseline in subjects receiving Regadenoson. We took measurements in patients who received Regadenoson, as well as Sickle Cell controls. Both arms had microvascular blood flow (volume x velocity) measured at baseline and 24-hours, and those values were compared. A change ratio of \>1 means that the flow rate increased at 24 hours and a change ratio of \<1 means that the flow rate decreased at 24 hours.

Secondary Outcome Measures

Name	Time	Method
Microvascular Blood Flow in Sickle Cell Anemia Subjects Versus Control Subjects	5 years	Examine microvascular blood flow using contrast-enhanced ultrasounds in adult subjects with sickle cell anemia compared to microvascular blood flow of healthy African-American adults
MVBF Ratio of Change During a Pain Crisis	Between baseline and between 7-30 days after pain crisis, if feasible	We planned to examine differences in microvascular blood flow using contrast-enhanced ultrasound (CEU) in adults with sickle cell anemia age 18 and older at baseline state compared to a pain crisis. We were measuring changes in microvascular blood flow in subjects with sickle cell anemia during a pain crisis by examining differences in microvascular blood flow using contrast-enhanced ultrasound at a baseline state, and comparing those measurements to contrast-enhanced ultrasound measurements during a pain crisis. A change ratio of \>1 means that the flow rate increased during a pain crisis and a change ratio of \<1 means that the flow rate decreased during a pain crisis.