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Intestinal Gel Eases Parkinson's Symptoms

Thursday September 26, 2013

Cole Petrochko

MedPage Today - Treatment with an intestinal levodopa-carbidopa gel administered through a gastrostomy tube improved patients' Parkinson's symptoms and health-related quality of life, researchers reported here.

At the end of a 54-week open-label trial, the intestinal gel was associated with significant improvements in patient mobility (P<0.001), activities of daily living (P<0.001), emotional well-being (P<0.001), sense of stigma (P<0.001), cognition (P<0.001), communication (P<0.001), and bodily discomfort (P<0.001), according to Alberto Espay, MD, of the University of Cincinnati Academic Health Center in Ohio, and colleagues.

Although the majority of patients experienced adverse events related to tube insertion, these adverse events resolved after 13 to 24 weeks, Espay said at an oral presentation during the World Congress of Neurology meeting.

The drug combination offers relief to Parkinson's disease symptoms, but "chronic treatment with standard formulations of oral levodopa is associated with the development of motor complications that can become disabling for some patients," Espay said, adding that "increasing evidence suggests that motor complications are due to nonphysiologic pulsatile stimulation of striatal dopamine receptors produced by the administration of intermittent doses of standard oral levodopa."

The authors studied whether a continuous levodopa therapy, delivered through a levodopa-carbidopa intestinal gel, would improve functional and health-related quality of life outcomes through a 54-week, open-label study of 317 Parkinson's disease patients with severe motor fluctuations despite optimized medical therapy.

Prior to baseline, patients were trained in keeping a diary and were stabilized on levodopa monotherapy for 28 days. After that screening period, a baseline assessment was taken that recorded disease duration, Mini-Mental State Exam score, daily dose of levodopa, "off" time, "on" time without troublesome dyskinesia, mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort.

For 2 to 14 days, participants had the gel administered via nasojejunal tube to test for tolerability and response to treatment. If successful, patients would have a percutaneous endoscopic gastrojejunostomy tube implanted through which gel was administered and dosing optimized over the next 2 to 14 days. They were then evaluated for up to the next 378 days. Only gel and immediate-release oral levodopa-carbidopa tablets were permitted following tube insertion, though other Parkinson's drugs other than apomorphine could be reintroduced at the researcher's discretion.

The primary endpoint was mean change from baseline in off time as written in the patient's diary. Secondary endpoints included on time without troublesome dyskinesia, on time with troublesome dyskinesia, Unified Parkinson's Disease Rating Scale, and assessments through the 39-item Parkinson's Disease Questionnaire.

Additionally, researchers logged adverse events.

Mean patient age was 64.1. The majority of patients were men (57.1%) and white (92.7%).

They had a mean disease duration at baseline of 12.5 years, a mean mental exam score of 28.4, a mean daily levodopa dose at screening of 1082.89 mg, a mean on time with troublesome dyskinesia of 1.61 hours, and a mean on time without troublesome dyskinesia of 7.65 hours. Mean off time was 6.75 hours.

Over the course of the intervention, on time without troublesome dyskinesia increased significantly (P<0.001) to around 12.4 hours, while off time decreased significantly (P<0.001) to around 2.3 hours. On time with troublesome dyskinesia decreased significantly (P<0.05) to around 1.2 hours.

Scores for motor symptoms, dyskinesia, and activities of daily living decreased significantly from baseline to the end of study (P<0.001 for all), as did patient-rated scores on the 39-item questionnaire (P<0.001).

Among adverse events, 92% experienced any adverse event, the most common of which were complications of device insertion (34.9%), abdominal pain (31.2%), and procedural pain (20.7%), though Espay noted that these procedure-related symptoms resolved commonly around weeks 13 to 24.

Other adverse events included nausea (16.7%), excessive granulation tissue (16%), postoperative wound infection (15.4%), fall (15.1%), constipation (14.5%), insomnia (13.6%), incision site erythema (13%), and urinary tract infection (11.4%). These events resulted in study withdrawal in 7.6% of patients. Two patients contemplated suicide and two committed a suicide.

Eight deaths occurred during the study, though they were not considered to be related to treatment.

"I'm struck by the improvement in the quality of life despite dealing with the inserted tube," remarked session moderator C. Warren Olanow, MD, of Mount Sinai School of Medicine in New York, N.Y.

Olanow, who was a co-investigator on another intestinal gel levodopa study, also noted a suicide risk in study participants. However, Espay could not draw any conclusions if such a risk was related to treatment and said that additional time and research would be needed before he could offer any final word.

Petrochko, C. (26 Sep. 2013). MedPage Today. Intestinal Gel Eases Parkinson's Symptoms. www.medpagetoday.com.

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