First Study of Its Kind Tests Drug for Pulmonary Hypertension in Sickle Cell Disease Patients

Saint Louis University researchers are recruiting volunteers who have both sickle cell disease and pulmonary hypertension to test the safety and effectiveness of a medicine already approved by the FDA to treat pulmonary arterial hypertension alone.

Pulmonary arterial hypertension, which is high blood pressure in the arteries that supply the lungs, is a deadly complication that affects 30 percent of patients who have sickle cell disease. More than 50,000 patients in the U.S. have both conditions. This is the first large multicenter clinical trial to examine a specific treatment for pulmonary hypertension in patients who have sickle cell disease. “Pulmonary hypertension is one of the main causes of death in patients who have sickle cell disease,” says Wilman Ortega, M.D., assistant professor of pulmonary, critical care and sleep medicine at Saint Louis University School of Medicine and principal investigator for the clinical trial. “If left untreated, a lot of patients with both conditions die within two and a half years.” Saint Louis University is one of 24 centers around the world, and the only one in Missouri, to study whether a medication is safe for and improves pulmonary blood pressure and the quality of life in patients who have sickle cell disease. Saint Louis University hopes to recruit 10 patients for the clinical trials, which will involve 236 patients worldwide. Those eligible must be over 18 years of age; have shortness of breath, which is a symptom of pulmonary hypertension; and sickle cell disease. As part of the screening for the study, potential participants will undergo an echocardiogram unless they’ve had the test within the past six months and not during a painful episode. They also will receive a pulmonary function test, which measures how much air they can breathe in and out, and will walk for six minutes to see if they experience breathlessness. Volunteers also will receive a right heart catheterization, unless they’ve had one within the last three months, to diagnose the severity and type of pulmonary hypertension they have. Of those who qualify for the clinical trials, half will receive an oral medication that blocks a hormone called endothelin, which constricts vessels and raises pulmonary artery pressures. The other half will receive a placebo. The oral medication will be given twice a day and the blood work of patients will be monitored every two weeks. If patients taking the active medication are tolerating it well, they will switch to a higher dosage of the drug after four weeks. After 16 weeks, all patients will have the option of receiving the active medication, probably for a year. “In addition to seeing if the medication is safe and effective in treating pulmonary hypertension in patients who have sickle cell disease, we will study if there is a decrease in the number of times these patients are hospitalized due to a sickle cell crisis,” Ortega says. “A sickle cell crisis can be triggered by infection and dehydration, and occurs when patients experience extreme pain in their legs, back, hips and chest because red blood cells become rigid and block blood vessels. We treat the symptoms with pain medications, antibiotics if there’s an infection, possible blood transfusions and fluids. However there is no specific treatment for sickle cell disease itself so far and more research is really needed in this area.” Sickle cell disease is a debilitating and painful genetic blood disorder that is most common among individuals of African ancestry, and also affects those of Mediterranean, Caribbean, South and Central American, Arabian and East Indian descent. Between 1 and 2 percent of those of African parentage have the disease, named for red blood cells that warp into a sickle shape when they are depleted of oxygen. The sickle shape makes it difficult for blood cells to flow through veins and arteries as easily as normal oval shaped blood cells. The blood vessels of patients who have pulmonary hypertension and sickle cell disease become thick and narrow, reducing the amount of blood that can flow through and causing the pressure to increase. This forces the heart to work harder to pump enough blood through the lungs, where it picks up oxygen. Eventually, the heart gives out. Patients who have sickle cell disease may not realize they have pulmonary hypertension if they are in the early stage of the illness before they have symptoms such as fatigue, dizziness and shortness of breath, Ortega says. He urges all patients who have sickle cell disease to be screened for pulmonary hypertension even if they have no breathing problems or other symptoms of the condition. “If they have sickle cell disease, they could easily have pulmonary hypertension. They need to go to their physician and make their doctors aware they should get an echocardiogram, which screens for pulmonary hypertension.”(Source: Saint Louis University: June 2006.)