Jeffrey Glassberg, MD, left, administered a lung-function test to Eric Gay, a participant in the clinical trial.
An inhaled treatment that might improve lung function— and reduce the painful symptoms—of patients with sickle cell disease (SCD) is being studied in a clinical trial funded by a $4 million grant from the National Institutes of Health awarded to researchers at the Icahn School of Medicine at Mount Sinai.
“Inhaled corticosteroids, a well-established treatment for asthma, offer a creative new approach to treating sickle cell disease, with the potential to dramatically improve patient outcomes,” says Jeffrey Glassberg, MD, principal investigator of the study, and Associate Professor of Emergency Medicine, and Medicine (Hematology and Medical Oncology). SCD affects about 100,000 people in the United States and is more prevalent in certain ethnic groups, such as African Americans and Hispanics.
he inherited disease is caused by a mutation in hemoglobin, a protein inside red blood cells that carries oxygen from the lungs to the rest of the body. In SCD, abnormal hemoglobin forms long rods and distorts red blood cells into a sickle shape. The repeated damage to red cells causes the blood to become inflamed and sticky, causing pain, infections, stroke, and potentially, early death. The only organs in the body that can reverse sickling are the lungs, but they are highly inflamed in SCD. That is why researchers have proposed using inhaled steroids as a treatment.
“We hypothesize that if patients take an asthma medicine that reduces inflammation in the lungs, it might improve their ability to put oxygen into their blood and make their sickle cell better,” says Dr. Glassberg, Director of the Comprehensive Program for Sickle Cell Disease at the Icahn School of Medicine. The phase II trial—Inhaled Mometasone to Promote Reduction in Vaso-occlusive Event (IMPROVE 2)—is seeking to recruit 80 patients who have sickle cell disease but do not have asthma. They will be randomized, with one group receiving a placebo and the other receiving an inhaled treatment of the steroid mometasone furoate once a day for 48 weeks. The dose will be low, 220 micrograms, to avoid side effects associated with steroids, such as weight gain or bone disorders.
The primary outcome studied will be the level of a biomarker called soluble vascular cell adhesion molecule (sVCAM). “This is something that you measure in the blood, and it correlates very well with how bad somebody’s sickle cell disease is at the time,” says Dr. Glassberg. “The sVCAM level goes up when they are sick, and it goes back down when they get better.” Patients will also keep a daily diary of their pain and quality of life, and return regularly for tests of lung function.
A prior study, IMPROVE 1, established the feasibility of the current trial, with results published in March 2017 in the American Journal of Hematology. It involved 52 patients, who took the inhaled treatment for 16 weeks. Sickle cell symptoms tend to be seasonal, with some patients reporting more pain in colder months, so Dr. Glassberg says the longer IMPROVE 2 study will provide a broader understanding of the treatment. His group is seeking to enroll 20 people a year and to complete the study in June 2023.
Dr. Glassberg sees a future role for inhaled steroids as part of a drug “cocktail,” along with drugs like hydroxyurea that interfere with sickling. A low-dose inhaled steroid treatment would work in concert with these drugs, improving the flow of oxygenated blood. “This is especially appealing because inhaled steroids are inexpensive, widely available, and do not require sophisticated equipment, so they can be used anywhere in the world,” Dr. Glassberg says. “I think this treatment has the potential for a big health impact.”
For information about enrollment in the clinical trial, call 212-241-3650.