Microvascular Blood Flow in Sickle Cell Anemia

NCT01566890 | Completed Results DMC

• 1 other identifier: DD2011101
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 2

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.

Conditions

Sickle Cell Disease; Sickle Cell Anemia

Keywords

sickle cell; sickle cell crisis; sickle cell pain crisis; vaso-occlusive crisis; vaso-occlusion; sickle cell anemia; sickle cell disease; genetic diseases; adenosine 2A Receptor Agonists; Lexiscan; Regadenoson; contrast-enhanced ultrasound; Hydroxyurea

Outcome Measures

Primary Outcomes (1)

• Microvascular Blood Flow Rate Change

  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.

  Between baseline and 24 hours

Secondary Outcomes (2)

• MVBF Ratio of Change During a Pain Crisis

  Between baseline and between 7-30 days after pain crisis, if feasible

• Microvascular Blood Flow in Sickle Cell Anemia Subjects Versus Control Subjects

  5 years

Study Arms (5)

Regadenoson ARM

EXPERIMENTAL

Adult subjects with sickle cell anemia will receive a regadenoson infusion with contrast-enhanced ultrasound

Drug: regadenoson infusion with contrast-enhanced ultrasound

Sickle Cell Controls ARM

OTHER

Adult subjects with sickle cell anemia will receive contrast-enhanced ultrasound

Procedure: contrast-enhanced ultrasound

Sickle Cell CEU ARM

OTHER

Adults subjects with sickle cell anemia will receive contrast-enhanced ultrasound

Procedure: contrast-enhanced ultrasound

Healthy Control ARM

OTHER

Healthy African American control subjects without sickle cell anemia will receive contrast-enhanced ultrasound

Procedure: contrast-enhanced ultrasound

Technique Optimization Controls

OTHER

Healthy volunteers will undergo contrast-enhanced ultrasound.

Procedure: contrast-enhanced ultrasound

Interventions

regadenoson infusion with contrast-enhanced ultrasound DRUG

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

Also known as: Lexiscan, regadenoson

Regadenoson ARM

contrast-enhanced ultrasound PROCEDURE

Subjects who are not having a pain crisis will have contrast-enhanced ultrasound performed up to four times over a two-day period. Time points will resemble the time course used for the Regadenoson Arm, although no investigational drug will be given.

Sickle Cell Controls ARM

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Versiti Blood Health: lead
• Medical College of Wisconsin: collaborator
• La Jolla Institute for Allergy & Immunology: collaborator
• University of Illinois at Chicago: collaborator
• Oregon Health and Science University: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (2)

The University of Illinois

Chicago, Illinois, 60607, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (4)

• Ashley-Koch A, Yang Q, Olney RS. Sickle hemoglobin (HbS) allele and sickle cell disease: a HuGE review. Am J Epidemiol. 2000 May 1;151(9):839-45. doi: 10.1093/oxfordjournals.aje.a010288.

  PMID: 10791557 BACKGROUND

• Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995 May 18;332(20):1317-22. doi: 10.1056/NEJM199505183322001.

  PMID: 7715639 BACKGROUND

• {Field, 2011 #10443}Field, J. J., D. G. Nathan, et al. (2011).

  BACKGROUND

• Belcik JT, Davidson BP, Xie A, Wu MD, Yadava M, Qi Y, Liang S, Chon CR, Ammi AY, Field J, Harmann L, Chilian WM, Linden J, Lindner JR. Augmentation of Muscle Blood Flow by Ultrasound Cavitation Is Mediated by ATP and Purinergic Signaling. Circulation. 2017 Mar 28;135(13):1240-1252. doi: 10.1161/CIRCULATIONAHA.116.024826. Epub 2017 Feb 7.

  PMID: 28174191 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Vaso-Occlusive Crises; Genetic Diseases, Inborn

Interventions

regadenoson

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

As with any study, ours had limitations. The most significant limitation was our small sample size.

Results Point of Contact

• Title: Joshua Field, MD
• Organization: Medical College of Wisconsin Department of Hematology

JField@Versiti.org

414-937-6896

Study Officials

• Joshua J Field, MD, MS

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• Jonathon Lindner, MD

  Oregon Health and Sciences University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 28, 2012
• First Posted: March 29, 2012
• Study Start: July 1, 2012
• Primary Completion: July 5, 2019
• Study Completion: November 16, 2020
• Last Updated: June 26, 2024
• Results First Posted: June 26, 2024

Record last verified: 2024-06

Locations

US (2)