CINCINNATI—An intestinal gel delivered via a surgically implanted tube works better for Parkinson’s disease patients than similar medication taken orally, according to the results of a recently concluded clinical trial whose sites included Cincinnati.
Use of the levodopa-carbidopa intestinal gel (LCIG) was found to reduce "off” time in patients with advanced Parkinson’s disease who participated in the phase-3 randomized, double-blind clinical trial. "Off” time occurs when Parkinson’s symptoms such as tremor, slowness, stiffness and walking difficulty return as the beneficial effects of oral treatments wear off.
Cincinnati was one of 11 U.S. sites that participated in the trial, supported by Abbott. (Three sites in New Zealand also participated.) The study co-author and principal investigator at the Cincinnati site was Alberto Espay, MD, an associate professor in the University of Cincinnati (UC) Department of Neurology and a UC Health neurologist with the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the UC Neuroscience Institute.
Results of the trial will be among the works Espay is presenting Thursday, April 26, in the Scientific Highlights in the Field of Movement Disorders session at the American Academy of Neurology’s (AAN) 64th annual meeting in New Orleans. Study results will also be presented as part of the Emerging Science program.
"The results of the LCIG clinical trial are robustly positive,” says Espay. "They provide encouraging data for its regulatory review and the framework for eventually implementing it as a therapy, with the potential to dramatically improve the quality of life in individuals with Parkinson’s disease disabled by severe motor complications.”
Parkinson’s disease is a chronic, degenerative neurological disorder in which certain dopamine-producing cells in a region of the brain begin to die. When these cells die, neurons in the brain fire erratically, leaving patients less able to direct or control their movements.
The delivery system used in the clinical trial feeds the commonly prescribed Parkinson’s drugs levodopa (the precursor of dopamine) and carbidopa into the upper intestine via a small tube inserted directly into the first part of the small bowel. The medication is suspended as a stable gel from a cassette worn outside the body. A programmable pump allows the patient or physician to adjust the delivery of medication.
"With other medications, the stimulus of dopamine receptors is given, then taken away, in multiple cycles,” says Espay. "But with this system, we’re basically bathing the patient’s brain in dopamine at all times. This gives patients the continuity of stimulation of dopamine receptors, and therefore more stability of function, that they can’t get with any other means. Our patients are also released from the shackles of having to take medication at certain times throughout the day.”
In Cincinnati, the tube was implanted at UC Health University Hospital by Nathan Schmulewitz, MD, who worked in cooperation with Espay on the clinical trial. Schmulewitz is an associate professor in the division of digestive diseases.
In the clinical trial, which lasted three months, 71 participants were randomized to receive either the continuous infusion of LCIG and dummy pills or a dummy intestinal gel and pills that contained levodopa and carbidopa. At the start of the study, the average person had Parkinson’s disease for about 11 years and experienced 6.6 hours of "off” time per day.
The study found that the continuous LCIG reduced "off” time by an average of nearly two extra hours per day and improved "on” time without troublesome movements by an average of two hours per day compared to people taking standard levodopa-carbidopa.
"Less ‘off’ time for people with Parkinson’s means more time during the day in which they can enjoy the benefits of levodopa-carbidopa therapy and experience improved quality of life,” says lead study author C. Warren Olanow, MD, professor of neurology and neuroscience at the Mount Sinai School of Medicine in New York and an AAN Fellow.
The most common side effects associated with LCIG treatment involved complications due to inserting the device, abdominal pain, pain during the procedure and nausea.
With the conclusion of the phase 3 trial, LCIG will undergo further study and review required before approval by the U.S. Food and Drug Administration. It is already approved in 40 countries outside the U.S.
Espay reports that he has received research support for the clinical trial and has received compensation from Solvay Pharmaceuticals (now Abbott) and Abbott for serving as a consultant and scientific advisory board member.