BY PEGGY O'FARRELL
Every morning, from about 8:30 to 10, Dan Truesdale froze up.
His muscles grew rigid, locked in place because of Parkinson's disease, until the medication finally kicked in, allowing to him get up, move around, live his life.
That changed last year when Truesdale, 47, became the first patient in Ohio to receive an experimental drug delivery system that gives his body a continual dose of the medication that lets him control his muscle movements.
His "frozen" muscles have thawed, Truesdale said.
"It's the best thing that's happened to me since I discovered I had Parkinson's," he said.
Researchers at the University of Cincinnati's Neuroscience Institute at University Hospital are recruiting more patients like Truesdale to test the system as part of a national phase 3 clinical trial.
Phase 3 trials are large-scale tests of new drugs or devices and the final step before federal health regulators decide to allow manufacturers to put new therapies on the market. Earlier phases test safety and effectiveness of new therapies on smaller scales.
Parkinson's disease is a chronic brain disorder in which brain cells that make the chemical dopamine die off. It usually strikes people over 50, and men are about 50 percent more likely to get it than women.
Without dopamine, adults lose control of muscle movements and balance. Symptoms get worse over time, said Alberto Espay, the neurologist heading up UC's arm of the trial, and Parkinson's patients may eventually lose the ability to speak, feed themselves, swallow or chew.
Replacing the lost dopamine helps patients regain muscle control, but standard treatments give dopamine in oral medications taken in several doses throughout the day.
That means the brain gets the dopamine it needs in interrupted allotments, so patients have periods throughout the day where they either can't move at all or they can't stop their bodies from moving involuntarily.
The drug delivery system Espay is testing aims to change that.
Abbott Pharmaceuticals' Levodopa-Carbidopa Intestinal Gel treatment system feeds the medication levodopa, which in the body becomes dopamine, into the upper intestine via a small tube surgically placed directly into the duodenum, or the very tip of the small intestine. The drug is fed through the tube from a cassette worn on the patient's body. A programmable pump lets the patient or doctor adjust the rate at which the medication is delivered.
"With this system, we're basically bathing the patient in dopamine at all times," Espay said.
Truesdale of Maineville used to be able to set his watch by his symptoms. The pump has changed all that. "I don't notice the passing of the hours because my symptoms have been reduced so drastically," he said.
He was diagnosed with Parkinson's in 2000, and has been on disability for the last four years. He recently began studying to become a minister.
The pump system is designed for patients like Truesdale with severe symptoms that are no longer controlled by standard medications, Espay said.
"People who've withdrawn from social and intellectual activities, they can resume them. We've seen people take up new activities after they've gone on the pump," he said.
Thursday, August 12, 2010
Parkinson's Disease Placebo Response Increases with Expectations
Individuals with Parkinson's disease were more likely to have a neurochemical response to a placebo medication if they were told they had higher odds of receiving an active drug.
Chicago, IL - infoZine - "The promise of symptom improvement that is elicited by a placebo is a powerful modulator of brain neurochemistry," the authors write as background information to a report in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals. "Understanding the factors that modify the strength of the placebo effect is of major clinical as well as fundamental scientific significance." In patients with Parkinson's disease, the expectation of symptom improvement is associated with the release of the neurotransmitter dopamine, and the manipulation of this expectation has been shown to affect the motor performance of patients with the condition.
Sarah C. Lidstone, Ph.D., of Pacific Parkinson's Research Centre at Vancouver Coastal Health and the University of British Columbia, Vancouver, Canada, and colleagues studied 35 patients with mild to moderate Parkinson's disease undergoing treatment with the medication levodopa. On the first day of the study, a baseline positron emission tomographic (PET) scan was performed, participants were given levodopa and a second scan was performed one hour later to assess dopamine response. On the second day, patients were randomly assigned to one of four groups, during which they were told they had either a 25-percent, 50-percent, 75-percent or 100-percent chance of receiving active medication before the third scan; however, all patients were given placebo.
Patients who were told they had a 75-percent chance of receiving active medication demonstrated a significant release of dopamine in response to the placebo, whereas those in the other groups did not.
Patients' reactions to the active medication before the first scan was also correlated with their response to placebo. "Importantly, whereas prior medication experience (i.e., the dopaminergic response to levodopa) was the major determinant of dopamine release in the dorsal striatum, expectation of clinical improvement (i.e., the probability determined by group allocation) was additionally required to drive dopamine release in the ventral striatum," the authors write. Both areas have been shown to be involved with reward processing; in patients with a chronic debilitating illness who have responded to therapy in the past, expectation of therapeutic benefit in response to placebo has been likened to the expectation of receiving a reward.
"Our findings may have important implications for the design of clinical trials, as we have shown that both the probability of receiving active treatment—which varies in clinical trials depending on the study design and the information provided to the patient—as well as the treatment history of the patient influence dopamine system activity and consequently clinical outcome," the authors conclude. "While our finding of a biochemical placebo response restricted to a 75 percent likelihood of receiving active treatment may not generalize to diseases other than Parkinson's disease, it is extremely likely that both probability and prior experience have similarly profound effects in those conditions."
This study was funded by the Michael Smith Foundation for Health Research, the Canadian Institutes for Health Research and a TRIUMF Life Sciences Grant. Dr. Stoessl is supported by the Canada Research Chairs Program.
Chicago, IL - infoZine - "The promise of symptom improvement that is elicited by a placebo is a powerful modulator of brain neurochemistry," the authors write as background information to a report in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals. "Understanding the factors that modify the strength of the placebo effect is of major clinical as well as fundamental scientific significance." In patients with Parkinson's disease, the expectation of symptom improvement is associated with the release of the neurotransmitter dopamine, and the manipulation of this expectation has been shown to affect the motor performance of patients with the condition.
Sarah C. Lidstone, Ph.D., of Pacific Parkinson's Research Centre at Vancouver Coastal Health and the University of British Columbia, Vancouver, Canada, and colleagues studied 35 patients with mild to moderate Parkinson's disease undergoing treatment with the medication levodopa. On the first day of the study, a baseline positron emission tomographic (PET) scan was performed, participants were given levodopa and a second scan was performed one hour later to assess dopamine response. On the second day, patients were randomly assigned to one of four groups, during which they were told they had either a 25-percent, 50-percent, 75-percent or 100-percent chance of receiving active medication before the third scan; however, all patients were given placebo.
Patients who were told they had a 75-percent chance of receiving active medication demonstrated a significant release of dopamine in response to the placebo, whereas those in the other groups did not.
Patients' reactions to the active medication before the first scan was also correlated with their response to placebo. "Importantly, whereas prior medication experience (i.e., the dopaminergic response to levodopa) was the major determinant of dopamine release in the dorsal striatum, expectation of clinical improvement (i.e., the probability determined by group allocation) was additionally required to drive dopamine release in the ventral striatum," the authors write. Both areas have been shown to be involved with reward processing; in patients with a chronic debilitating illness who have responded to therapy in the past, expectation of therapeutic benefit in response to placebo has been likened to the expectation of receiving a reward.
"Our findings may have important implications for the design of clinical trials, as we have shown that both the probability of receiving active treatment—which varies in clinical trials depending on the study design and the information provided to the patient—as well as the treatment history of the patient influence dopamine system activity and consequently clinical outcome," the authors conclude. "While our finding of a biochemical placebo response restricted to a 75 percent likelihood of receiving active treatment may not generalize to diseases other than Parkinson's disease, it is extremely likely that both probability and prior experience have similarly profound effects in those conditions."
This study was funded by the Michael Smith Foundation for Health Research, the Canadian Institutes for Health Research and a TRIUMF Life Sciences Grant. Dr. Stoessl is supported by the Canada Research Chairs Program.
Subscribe to:
Posts (Atom)
