Continuous Duodenal Levodopa Infusion – The Barcelona Experience © T
Published: November 2008
Parkinson’s disease (PD) is a highly debilitating, progressive disease that responds favourably to therapeutic doses of levodopa, the gold standard treatment for PD. Treatment of PD is largely determined by the phase of the disease the patient is currently experiencing: early, middle or advanced. Initially, there is good response to medication and adjuvant therapeutic strategies, but after six to eight years motor and non-motor complications develop. These are produced in part by erratic gastric emptying leading toirregular absorption and fluctuating plasma levels of levodopa, and hence an unstable response. At this point, clinical fluctuations are progressively more difficult to control and, consequently, the quality of life of patients deteriorates. The development of deep brain stimulation for the treatment of these long-term PD patients has been a major step forward. More recently, a novel gel form of levodopa/carbidopa has enabled infusion through percutaneous endoscopic gastrostomy directly into the duodenum. This system avoids the gastric step, enhancing absorption of the drug and favouring stable plasma levels of levodopa. The advantages of this approach have since been considered in several clinical studies. In order to investigate the clinical effects of intraduodenal levodopa infusions on motor fluctuations and to explore the safety issues, we have conducted a multicentre prospective study in the area of Barcelona (Catalonia, Spain). The preliminary results of this study in 26 patients are presented here and discussed together with the recommended management, from our experience, of the most frequent adverse effects and mechanical complications of the infusion device that we have observed.
Our as-yet quite short experience with continuous levodopa infusion (Duodopa) therapy at the University of Barcelona began 18 months ago. We decided to include patients who fulfilled the following criteria:
- advanced idiopathic Parkinson’s disease (PD);
- absence of associated diseases limiting survival;
- good response to levodopa;
- motor fluctuations;
- all available oral therapy exhaustively tested;
- absence of severe cognitive problems;
- absence of active psychiatric complications; and
- good support from family/care-givers.
Our contraindications, which are in common usage, were:
- glaucoma
- severe hepatic or cardiac insufficiency;
- cardiac arrhythmia;
- stroke;
- treatment with non-selective monoamine oxidase (MAO) inhibitors
or MAO-A inhibitors; and
- phaeochromocytoma, Cushing’s syndrome and/or hyperthyroidism.
Objectives and Methods
The objective of the study was to analyse the efficacy and safety of continuous duodenal levodopa infusion in a subset of patients with advanced PD and severe motor fluctuations not optimally controlled with standard oral therapies. It was an open-label study with no group control and no blinded evaluations. Assessments were performed using the Unified Parkinson Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) staging and patient home diaries at baseline and at three-, sixand 12-month follow-up. At the time of writing, only three patients have data beyond 12 months.
At the start of the trial, patients initially received continuous duodenal levodopa infusion through a nasoduodenal tube in order to test their response. Responders underwent a percutaneous endoscopic gastrostomy (PEG) to have the permanent tube inserted. During the recruitment period we processed 15 suitable candidates who had a nasoduodenal tube inserted. Thirteen of these accepted PEG. Those who did not accept PEG either had superior expectations that were not met by the preliminary infusion or experienced hallucinations during this testing phase (see Figure 1).
Table 1 shows the clinical characteristics of all 15 patients initially recruited into the trial. The age of the cohort is particularly interesting as it is on average slightly higher than would be expected with candidates for deep brain stimulation (DBS), and similarly the disease duration was longer. All patients were already on high doses of levodopa (>800mg/day) and seven patients had received previous surgery: DBS and/or pallidotomy. Off time was prolonged in all but one subject, at more than 50% on average.
levodopa infusion, Parkinson’s disease, phaeochromocytoma
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