Trial record 1 of 4 for:    Lexiscan AND sickle
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Microvascular Blood Flow in Sickle Cell Anemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by Blood Center of Wisconsin
Sponsor:
Collaborators:
Medical College of Wisconsin
La Jolla Institute for Allergy & Immunology
University of Illinois at Chicago
Oregon Health and Science University
Information provided by (Responsible Party):
Joshua Field, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01566890
First received: March 28, 2012
Last updated: November 30, 2012
Last verified: November 2012
  Purpose

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.

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


Condition Intervention
Sickle Cell Disease
Sickle Cell Anemia
Drug: regadenoson infusion with contrast-enhanced ultrasound
Procedure: contrast-enhanced ultrasound

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Effect of Adenosine 2A Receptor Agonist Regadenoson on Microvascular Blood Flow in Sickle Cell Anemia

Resource links provided by NLM:


Further study details as provided by Blood Center of Wisconsin:

Primary Outcome Measures:
  • Microvascular Blood Flow in Sickle Cell Anemia with Regadenoson Use [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    To determine changes in microvascular blood flow using contrast-enhanced ultrasound in adults with sickle cell anemia before, during and after a 24 hour infusion of regadenoson


Secondary Outcome Measures:
  • Microvascular Blood Flow in Sickle Cell Anemia with Hydroxyurea Use [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To determine changes in microvascular blood flow using contrast-enhanced ultrasound in sickle cell anemia subjects before, during and after 3 months of hydroxyurea therapy

  • Changes in Microvascular Blood Flow in Subjects with Sickle Cell Anemia During a Pain Crisis [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To examine differences in microvascular blood flow using contrast-enhanced ultrasound in adults with sickle cell anemia at a baseline state compared to contrast-enhanced ultrasound measurements during a pain crisis

  • Microvascular Blood Flow in Sickle Cell Anemia Subjects Versus Control Subjects [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 103
Study Start Date: July 2012
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regadenoson ARM
Adult subjects with sickle cell anemia
Drug: regadenoson infusion with contrast-enhanced ultrasound
Subjects who are not having a pain crisis receive a 24-hour infusion of regadenoson. Contrast-enhanced ultrasound will be performed four times during the 24 hour regadenoson infusion
Other Name: Lexiscan
Hydroxyurea ARM
Adult subjects with sickle cell anemia
Procedure: contrast-enhanced ultrasound
Subjects will take oral hydroxyurea for 3 months and contrast-enhanced ultrasound will be performed three times during this 90 day period
Sickle Cell Anemia ARM
Adults subjects with sickle cell anemia
Procedure: contrast-enhanced ultrasound
Contrast-enhanced ultrasound will be performed on adults with sickle cell anemia at baseline who are not having a pain crisis and performed again during a pain crisis
Control ARM
Healthy African American control subjects without sickle cell anemia
Procedure: contrast-enhanced ultrasound
Contrast-enhanced ultrasound will be performed on healthy control subjects at baseline, on the first day of the study and 30 days later
No Intervention: Technique Optimization Controls
Healthy volunteers will undergo contrast-enhanced ultrasound.

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 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 the sickle cell therapies regadenoson and hydroxyurea will be examined. Contrast-enhanced ultrasounds will also be performed in individuals who are not having a sickle cell crisis and compared to CEU's from the same person while they are having a sickle cell crisis. 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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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

Hydroxyurea 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
  • Clinical indication for the initiation of hydroxyurea therapy per the treating physician
  • Successful completion of 70% of the hydroxyurea diary

Sickle Cell ARM Inclusion Criteria:

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

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 Definity a contrast agent

Hydroxyurea Treatment Exclusion Criteria:

  • Greater than 15% hemoglobin A1
  • Known or suspected right to left sided cardiac shunts
  • Chronic transfusion therapy
  • Receiving other investigational study agents, or have received a study agent within the last 30 days
  • Pregnant or breastfeeding
  • Subjects who have a HIV infection
  • Subjects who have had a hematopoietic stem cell transplant
  • Prior hypersensitivity reactions to Definity a contrast agent

Sickle Cell ARM Exclusion Criteria:

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

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 including
  • Pregnant or breastfeeding women
  • Subjects who have a HIV infection
  • Prior hypersensitivity reactions to Definity a contrast agent

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 Definity a contrast agent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01566890

Contacts
Contact: Joshua Field, MD, MS 414-937-6896 joshua.field@bcw.edu
Contact: Jillian Dargatz, RN 414-937-3859 jillian.dargatz@bcw.edu

Locations
United States, Illinois
The University of Illinois Recruiting
Chicago, Illinois, United States, 60607
Contact: Robert F. Machado, MD       machador@uic.edu   
Contact: Nancy G Casanova, MD    (312) 355-5934    ngcasan@uic.edu   
Principal Investigator: Roberto F. Michado, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Principal Investigator: Joshua Field, MD, MS         
Principal Investigator: Jonathon Lindner, MD         
Sponsors and Collaborators
Blood Center of Wisconsin
Medical College of Wisconsin
La Jolla Institute for Allergy & Immunology
University of Illinois at Chicago
Oregon Health and Science University
Investigators
Principal Investigator: Joshua Field, MD, MS Medical College of Wisconsin
Principal Investigator: Jonathon Lindner, MD Oregon Health and Sciences University
  More Information

Publications:
Responsible Party: Joshua Field, Principal Investigator, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01566890     History of Changes
Other Study ID Numbers: DD2011101
Study First Received: March 28, 2012
Last Updated: November 30, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Blood Center of Wisconsin:
sickle cell
sickle cell crisis
sickle cell pain crisis
sickle cell anemia
sickle cell disease
Lexiscan
Regadenoson
vaso-occlusive crisis
vaso-occlusion
genetic diseases
adenosine 2A Receptor Agonists
contrast-enhanced ultrasound
Hydroxyurea

Additional relevant MeSH terms:
Anemia, Sickle Cell
Regadenoson
Anemia
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Hydroxyurea
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antisickling Agents
Hematologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Adenosine A2 Receptor Antagonists
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014