Trial Information

Summary: Role of Placenta Growth Factor in Sickle Acute Chest Syndrome

What is Acute Chest Syndrome?
Patients with sickle cell disease (SCD) can suddenly develop a pneumonia-like inflammation of the lungs called Acute Chest Syndrome (ACS). Very little is known about the causes of ACS. The presence of an increased number of white blood cells, called inflammation, is associated with ACS. Laboratory tests have shown that some chemicals, such as placenta growth factor, cause this inflammation. These chemicals can produce asthma-like symptoms and can worsen lung function or symptoms of ACS.

What is the purpose of this study?
The goal of this study is to find out which tests (obtained on blood, urine, chest radiography and pulmonary functions) can predict the development of ACS in patients with sickle cell disease that are: 1) at baseline or at steady state 2) at the time of a vaso-occlusive event 3) during development of ACS.

Who will be included in this study?
Patients with sickle cell disease who are aged 7 to 30 and who are diagnosed with HbSS, HbSC, or HBSthal are eligible to participate in this research study.

What is involved?
Patients may be enrolled on the study for a maximum of 18 months.

The following tests will be performed during the baseline measurements. Baseline measurements are a group of measurements/tests that are performed when you are well, meaning that you are not sick or hospitalized.

• Approximately 1.5 tablespoons (21 mL) of blood will be collected for measurement of PlGF, other factors, and to determine the relationship between oxygen and hemoglobin in your blood. These specimens will be drawn at the same time you are having blood drawn for your routine medical care
• Approximately 2 tablespoons (25 mL) of urine will be collected for measurement of molecules that can cause ACS
• Chest X-ray with front and side views
• Echocardiogram testing. Most patients with sickle cell disease have echocardiograms done as part of their routine care. An echo (echocardiogram) is a test that helps doctors evaluate the strength and function of the heart. The test uses sound waves to create a picture of the heart. Before you have the Exercise Stress test (listed below), we will review your latest echo test results. If you have not had an echocardiogram before or if it has been a long time since your last echo, you will have one done as part of standard of care. This test will take about 30 minutes
• Resting pulmonary function test and graded exercise stress test. These tests will take about two hours to perform
  • To perform the pulmonary function tests, you will be asked to breathe in and out of various machines according to specific directions. These tests are not painful or uncomfortable. They involve no medications, injections, blood drawing, or discomfort. Although we are doing these tests for the purpose of this research study and not for your clinical care, these are standard tests that have been used for many years in the diagnosis of patients with lung disease
  • During the lung exercise test, you will be asked to exercise by walking or running on a treadmill for as long as you can. You will breathe in and out through a mouthpiece and have some electrodes taped on your skin. The speed and uphill grade of the treadmill will be increased every minute so that it will be more difficult for you to continue. You will be asked to continue running as long as you can

Repeat Baseline Measures
Because it is so important that your baseline measurements be done when you are well, the baseline measurements will need to be repeated in the following circumstances.

• If within three weeks after you have a baseline measurement, you go on to develop an acute sickle event (ACS, pain crises, fever, stroke, splenic sequestration [enlarged and painful spleen], hemolytic crisis or priapism [painful erection]), the measurements will be repeated during a routine visit when you are well
• If during the course of your participation in this research study, you develop ACS during a monitored hospitalization and it has been greater than one year since your baseline measurements, the baseline measurements will be repeated at least four weeks after your discharge from the hospital for the ACS event. These tests will be performed during your routine follow-up visit with your physician

Measurements During Hospitalization (when you are not well)
If you are hospitalized within the next 18 months, measurements will begin within the first 24 hours of your admission for an acute sickle event and will be done daily for a maximum four days. An acute sickle event is defined as hospitalization for one of the following: vaso-occlusive pain crises, fever with or without a known source of infection, cough/wheezing/chest pain, suspected or impending acute chest syndrome, splenic sequestration (enlarged and painful spleen), or priapism (painful erection). Testing will stop immediately if you develop ACS within the four-day monitoring period. The study will not interfere with the treatment you are being given while you are admitted.

You will be followed during each hospitalization while you are on this study until you have a hospitalization where you develop ACS on day three or later from admission. You will have a routine medical examination when admitted for an acute event. This will consist of a medical history, measurement of height, weight, vital signs (blood pressure, heart rate, and temperature), pulse-oximetry, and palpation of the liver and spleen. Routine labs will be done including complete blood count, reticulocyte count, chemistries, and C-reactive protein. While you are on study, we will collect information from your medical record related to any routine care you receive. All tests except the pulse-oximetry and chest x-rays (if you have lung symptoms) will be done for research purposes only.

The following tests will be performed daily during hospitalization

• Approximately 1.5 tablespoons (21 mL) of blood will be collected for measurement of PlGF, other factors and to determine the relation between oxygen and hemoglobin in your blood. These specimens will be drawn at the same time you are having blood drawn for your routine medical care
• Approximately 2 tablespoons (25 mL) of urine will be collected for measurement of molecules that can cause ACS
• Chest X-ray
• Bedside spirometry and pulse oximetry. Spirometry is a test that can be done while you are in your hospital bed. It measures how quickly your lungs can move air in and out and how much air they can move in and out. For this test, you breathe into the mouthpiece attached to a recording device (spirometer). This test takes about five minutes. Pulse oximetry is a test that measures the amount of oxygen in your blood. This test requires wearing a simple clip on your finger (pulse-ox) and is part of routine hospital care. We will also record the information for this study.

What are the benefits?
You may benefit from the additional medical tests that are a part of this study, such as the pulmonary function tests. The information learned from this research study may benefit other patients with ACS and sickle cell disease in the future.

Will I get all the facts about the study?
Parents interested in having their child participate, as well as adult patients/subjects, will be scheduled with a physician who will thoroughly explain all of the details of the study. The physician will review the consent form with the parent/guardian/adult subject and will be sure that all questions are answered. The consent form goes over all of the procedures, the risks, the benefits, the compensation, who to contact with questions or concerns and more. Study procedures will not begin until a parent/guardian or adult subject has signed this form and, if of age, the child has given at minimum his/her verbal agreement.

What are the risks?
A detailed list of side effects will be provided to those patients interested in knowing more about the study.

For more information,

If you would like to learn more about participating in this study, please send an e-mail message using the form below.