Amphetamines, Coupled with Physical Therapy, May Improve Functional Abilities of Stroke Patients
DURHAM, N.C. -- While much attention has focused on preventing stroke and much research has focused on limiting damage immediately after stroke, a Duke University Medical Center neurologist believes that not enough effort has been spent on improving recovery after stroke, a disorder that strikes more than 760,000 Americans each year.
Based on the positive results of animal studies and small clinical studies conducted at Duke and elsewhere during the past 10 years, Dr. Larry Goldstein believes that a new approach may improve patients' recovery after stroke -- adding small doses of amphetamines to a customized physical therapy program.
Because of the encouraging results of these earlier studies, Goldstein has organized a larger, five-center clinical trial to better understand and refine this new approach. The National Institute of Neurologic Disorders and Stroke (NINDS), a part of the National Institutes of Health, has granted the Goldstein-led group $1.1 million to conduct the trial.
"If the current study supports earlier, preliminary findings, this would open up a whole new avenue of therapy with the potential to improve the recovery of patients after stroke," Goldstein said."Not only might we be able to improve their functional abilities, but we might be able to decrease the huge costs associated with their long-term care.
"This is one of the first large, multi-center, randomized controlled trials aimed at a pharmacologic approach to post-stroke recovery," he said. "If positive, the study could lead to treatments having a major impact in improving the quality of life for stroke patients."
Goldstein is the principal investigator of the group that will enroll patients at Duke University Hospital, Wake Forest University Medical Center in Winston-Salem, N.C., Washington University in St. Louis and New York's Burke Rehabilitation Center and Helen Hayes Hospital. Patients will be enrolled in the study within 30 days of their stroke. All will receive personalized physical therapy tailored to their specific physical deficits. Half of the patients also will receive small doses of amphetamines and half will receive a placebo. Researchers, therapists and patients will not know until after the trial which patients received the active drug.
To be eligible for the trial, patients must have suffered an ischemic stroke, which occurs when blockages in blood vessels cut off blood supply to portions of the brain, causing damage or death to brain cells. These types of stroke represent 85 percent of all strokes, with the rest of the cases due to bleeding within the brain.
It is known that physical therapy within the first 60 days after a stroke can improve such functional abilities as walking, as well as arm and hand movements, Goldstein said. The researchers believe that the addition of amphetamines to the physical therapy regimen can "boost" the beneficial effects of the physical therapy. The researchers plan to time the ingestion of the amphetamines so that peak levels of the drug will be circulating through the bloodstream during the actual physical therapy.
"While we don't know exactly why it works, it appears that the amphetamines actually intensify the positive effects of the physical therapy on recovery," Goldstein said. "Somehow, the amphetamines seem to help in the relearning process. The brain is not a static organ -- it responds to injuries. While brain cells generally do not regenerate in adults, they are very dynamic and under the right conditions are subject to changes in performance."
Amphetamines are a class of drugs that stimulate the central and peripheral nervous systems. It is known that amphetamines stimulate the brain to release several chemicals called neurotransmitters, including norepinephrine, that can aid the passage of information between nerve cells.
"We believe that increasing the release of norepinephrine can lend further plasticity to brain, in effect helping the brain recover from the injury," Goldstein explained.
The trial will have two phases. If little improvement is seen in the first phase, the second phase will involve adjusting the dosage of amphetamines and the duration of the physical therapy. However, if clear improvement is seen during the first phase, the second phase will involve changing the timing of physical therapy sessions to see if the benefits can be achieved more quickly.
Researchers plan to enroll 65 patients into each phase of the trial.
Running concurrently will be an adjunct trial involving the use of amphetamines and physical therapy for patients whose stroke occurred between one month and six months previously. The goal, according to Goldstein, is to see if this new approach has any beneficial effects long past the initial stroke. This second trial is only being conducted at Duke, will involve 50 patients and is also supported by the NINDS.