Novo Nordisk Opens Observational Study of How Hemophilia Affects the Brain in Young People

Novo Nordisk is inviting children and young adults with hemophilia A and B to take part in its observational study of how this disease affects brain development, thinking, and behavior.

Results will help researchers better understand how advances in hemophilia treatment, like routine prophylaxis, impact the brain by establishing “a hemophilia normative dataset for neurologic, neurocognitive, and neurobehavioral function and development.”

Findings may also help in identifying children and adolescents at risk of cognitive and behavioral problems.

The trial’s observational (no treatment) design, along with a review of previous studies focused on brain development in these patients, were published in the journal Pediatric Blood & Cancer in the article “Neuropsychological function in children with hemophilia: A review of the Hemophilia Growth and Development Study and introduction of the current eTHINK study.”

Hemophilia is a genetic bleeding disorder most common to males, estimated to affect 20,000 people in the U.S. It is caused by a deficiency of either clotting factor VIII (hemophilia A, 80%) or factor IX (hemophilia B, 20%).

Many patients are treated at hemophilia centers, which offer specialized care. Incorporation of routine prophylatic, or preventive, factor replacement therapy has improved life for many with bleeding disorders.

“However, despite the more widespread use of factor replacement therapy to limit symptoms of physical disability in children with severe hemophilia, little is known about the impact of the disease on their cognitive development,” the researchers wrote.

Most of what is known about brain development and function in these patients comes from the Hemophilia Growth and Development Study (HGDS) conducted in the early 1990s, a time when treatment regimens and comorbidities — other conditions or diseases occurring simultaneously — differed significantly from those of today.

HGDS was a four-year observational study initiated in 1988 to understand the impact of hemophilia and HIV (a common comorbidity at the time) on brain development in 333 male children and adolescents with moderate to severe hemophilia in the U.S.

Results showed that hemophilia was associated with substantial brain dysfunction, represented not only by problems with coordination and motor function, but also lower intelligence, academic and adaptive skills, and more behavioral/emotional problems compared to published norms.

The data also highlighted an association between greater difficulties in performance skills, academic achievement, language, and nonverbal intelligence and memory in people with an impaired immune system linked to HIV infection.

Other studies in boys and men with hemophilia, conducted around the same era as HGDS, suggested they are at a greater risk of developing attention‐deficit/hyperactivity disorder (ADHD)-related problems, and more emotional, behavioral, and family difficulties. Also, intracranial hemorrhage (bleeding inside the skull) and a high number of overall bleeding events were independently associated with poorer cognitive function and worse school performance.

“In the [HIV] and pre-prophylaxis era, the HGDS and other studies demonstrated that hemophilia has an impact on the cognitive performance, behavior, and attention of affected males,” the team wrote.

To evaluate whether advances in hemophilia therapies have lessened the risk of cognitive and behavioral problems in these patients, Novo Nordisk designed the Evolving Treatment of Hemophilia’s Impact on Neurodevelopment, Intelligence, and Other Cognitive Functions (eTHINK) study (NCT03660774).

The company expects to enroll about 510 boys and young adults (1 to 21 years old) with hemophilia A and B across severity levels and therapy regimens, treated at hemophilia centers in the U.S.

Researchers will conduct a comprehensive examination of participants’ brain function, including an assessment of intelligence, emotional behavior, adaptive behavior, executive function, and attention and processing speed, with standardized tests and questionnaires (completed by patients or their parents/caregivers).

“The cross‐sectional eTHINK study will provide an updated [brain function] assessment across the spectrum of hemophilia severity and potentially point to predictors of risk for children with hemophilia,” the researchers stated.

They also noted that predictors of cognitive and behavior problems may be used to implement screening programs, and that results of the eTHINK study may identify treatment regimens with a potential impact on brain function and development in young people with bleeding disorders.