A Randomized, Single-blind Trial on the Efficacy and Safety of L-dopa Monotherapy Versus Dopamine Agonists Monotherapy After Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease

Background Information Deep Brain Stimulation (DBS) of the Subthalamic nucleus (STN) is an established treatment for patients with advanced Parkinson's disease (PD). STN DBS improves dopaminergic drug-sensitive motor symptoms, thus allowing a reduction in post-operative drug dose. The reduction of antiparkinsonian therapy in turn alleviates L-dopa-induced motor fluctuations and dyskinesias. However, a considerable variation in the extent of dopaminergic drug reduction has been reported, with values ranging from 20% to 100%. To date the management of antiparkinsonian medication after STN DBS mainly rely on neurologist's personal experience or patient's preference, as no evidence-based guidelines have been provided so far, with the exception of some pragmatic recommendation on postoperative issues promoted by the Movement Disorders Society in 2006.

Rationale for the study, potential risks and benefit In the immediate postoperative period following STN DBS, simplification of the medication regimen is advised, given the complexity of the interactions between stimulation and medication. Both L-dopa and DAs can be used, however, there are no formal studies examining which type of antiparkinsonian medication may be more effective and/or better tolerated following STN DBS. In spite of the need of simplification of the medication regimen after STN DBS in PD, to date there are no clinical trials specifically designed to compare the efficacy (in terms of motor and non-motor outcomes) and safety of L-dopa monotherapy versus DAs monotherapy following STN DBS.

Description of the population to be studied Patients with Parkinson's disease in advanced stage who undergo STN DBS. After one months since surgery, during the first programming visit, patients will be randomized in two groups receiving either L-dopa monotherapy or DAs monotherapy (either with pramipexole or ropirinole) for 2 months.

Study objectives and hypothesis Aim of our study is to compare the efficacy and the safety of L-dopa monotherapy versus DAs monotherapy after STN DBS over a 3-month follow up period. The hypothesis is that DAs may be more efficacious than L-dopa in treating non-motor symptoms after surgery, thus further improving quality of life following surgery. On the other hand, in comparison with L-dopa, DAs might be associated with more side effects (in particular impulse control disorders) and less effective motor control.

Study design This study is a prospective, single blind trial with a randomized-pairs design comparing L-dopa monotherapy and DAs monotherapy after STN DBS. The trial will be a single-center pilot study, conducted at Toronto Western Hospital, Toronto, Canada. The protocol meets the Ethical Conduct for Research Involving Humans. All patients will provide written informed consent. A total of 40 patients is estimated to be enrolled (20 patients for each treatment group). Duration of the study is 15 months. Enrollment will last for 12 months. The center will enroll patients in pairs, with one patient randomly assigned to L-dopa monotherapy and the other to DAs monotherapy after STN DBS. Randomization will be performed generating a random sequence of number through block randomization. Treatment assignment will be unmasked for the patient but will be blinded for the neurologist programming DBS and evaluating the patient. Another neurologist will be in charge of medication adjustments. Randomization, monitoring, and data management and analysis will be performed at the Toronto Western Hospital.