Children across the world with sickle cell disease will benefit from an $18.5 million National Institutes of Health (NIH) grant awarded to School of Medicine researchers to determine the effectiveness of blood transfusion therapy as a treatment for preventing silent strokes.
Silent strokes, which frequently go unrecognized, are one of the most serious afflictions associated with sickle cell disease. They can cause declines in school performance, increased forgetfulness and a diminished ability to follow even simple instructions.
“Regardless of the outcome of the study, our results will change the standard of care for children with sickle cell disease throughout the world,” said lead investigator Michael R. DeBaun, M.D., associate professor of pediatrics and of biostatistics. “At the end of the study, we will know whether blood transfusion therapy will prevent silent strokes in children with sickle cell disease.
“If there is a significant benefit, the standard of care will be changed for these vulnerable patients. And even if no benefit is detected, then patients will not be subject to unnecessary therapy.”
The grant — the most ever awarded to a pediatrician at the medical school — will fund a six-year international clinical trial at 22 sites, including ones in France, Canada and England.
DeBaun’s preliminary research at St. Louis Children’s Hospital over the past decade has revealed that silent strokes seriously affect children’s educational attainment and can lead to further neurological damage. His team recently completed a pilot trial showing that blood transfusion therapy is a safe and potentially effective therapy for children with silent strokes.
Sickle cell disease, an inherited disorder of the red blood cells, is the most common genetic disorder in African-Americans. The disease affects one in 400 African-American infants — and 20 percent of those children will suffer a silent stroke before they finish high school.
In sickle cell disease, red blood cells change to a curved, or sickle-shaped, instead of the normal, round shape. Sickle cells become stuck in blood vessels, causing damage to tissues and organs, which can be extremely painful.
In addition to pain, the most common afflictions associated with sickle cell disease are silent and overt strokes, kidney and spleen dysfunction, chronic anemia and increased risk of bacterial infection.
The only way to detect a silent stroke is to take pictures of the brain by using magnetic resonance imaging (MRI). Until now, there has been no systematic strategy to identify or treat children with silent strokes.
“It is crucial to recognize and treat children with silent strokes, because kids who have them are at a 24 percent risk over the next three years for further silent and overt strokes, which leave marked physical defects and cognitive deficits,” DeBaun said.
The standard treatment for overt strokes in children with sickle cell disease is blood transfusion therapy. The NIH grant will allow DeBaun and his international team of researchers to investigate whether blood transfusion therapy will also prevent silent strokes.
For three years, DeBaun’s group will randomly allocate blood transfusion therapy to 50 percent of the study participants, and the other half will be observed.
“If blood transfusion therapy is effective, the magnitude of this benefit for children with silent strokes will be tremendous,” DeBaun said.
The groundbreaking trial will enroll 1,880 children from around the world. All the children will have an MRI performed on their brains to detect silent strokes.
In addition, a blood sample will be collected to establish the world’s largest DNA repository for children with sickle cell disease — which will allow future genetic research to explore the genetic basis for stroke and other sickle cell-related diseases.
Patients receiving the preventive blood transfusion therapy will be transfused at three-to-four week intervals as needed to maintain healthy hemoglobin levels. MRIs will also be performed to detect new strokes and the progression of brain lesions at the beginning of the study, again at 12 months to 18 months and at the study’s completion.
“We have a once-in-a-lifetime opportunity to not only improve the quality of life for children currently afflicted with this disease,” DeBaun said, “but to also change the treatment and understanding of the disease for future generations of both patients and pediatricians.”