Treatment in advanced Parkinson*s disease: continuous intrajejunal levodopa infusion versus deep brain stimulation; a feasibility study

Neurologists and patients tend to choose more often for Continuous intrajejunal
Levodopa Infusion (CLI) than Deep Brain Stimulation (DBS) for the treatment of
advanced Parkinson*s disease (PD), although the efficacy of CLI is not
convincingly demonstrated. Without direct comparative data, this situation will
continue. A comparative study would provide a scientific basis for the
treatment choice in advanced PD. We submitted an application with The
Netherlands Organization for Health Research and Development (ZonMw) for
funding of a larger comparative study of CLI and DBS. Although the committee
considered the study design as good and the research question as relevant, the
request was declined with the argument that strong patient preferences
regarding the fairly invasive procedures would affect inclusion negatively, to
such an extent that the study would be not feasible. Since the influence of
patient preference in this context is unknown, we propose a pilot trial to
evaluate feasibility. This will give a strong argument as to whether a
randomized comparative trial would be feasible.

The primary objective of the proposed feasibility study is to determine the
willingness of patients to be randomized to CLI or DBS. Furthermore it will
serve as a pilot trial for a future larger randomized controlled trial. For
this larger trial, that will only be carried out if feasibility has been
confirmed, the objective is to determine whether CLI or DBS is a better therapy
in advanced PD. The pilot-trial will give a detailled insight in the
implementation of a possibile research protocol for the future larger study,
including possible outcome measures.

The feasibility study will consist of two elements: a cross-sectional study
assessing the willingness for randomization to CLI or DBS and a prospective,
randomized, open label multicenter pilot-trial including the patients that are
willing to be randomized. In the pilot-trial, patients will be randomized to
CLI or DBS. For CLI treatment, a tube will be placed in the jejunum via a
percutaneous endoscopic gastrostomy (PEG). This tube is connected to an
external pump that delivers the levodopa-gel. For DBS treatment, 2 electrodes
will be implanted in the brain. The electrodes are connected to an implanted
pulse generator, which will be placed subcutaneously in the subclavian area.

For CLI treatment, a tube will be placed in the jejunum via a percutaneous
endoscopic gastrostomy (PEG). This tube is connected to an external pump that
delivers the levodopa-gel. For DBS treatment, 2 electrodes will be implanted in
the brain. The electrodes are connected to an implanted pulse generator, which
will be placed subcutaneously in the subclavian area.

The study investigates the feasibility of a future larger study comparing CLI
and DBS. Both treatments are currently available for advanced PD and both have
a small risk of serious side effects.

Patients that are included in the cross-sectional study and do not want to
participate in the pilot trail will be asked to complete a questionnaire on
their motives to decline randomization. This is estimated to take 15 minutes.

For included patients that agree with randomization, the surplus in burden of
study participation compared to the regular treatment consists of both more and
more detailed assessment procedures. We estimate these extra procedures *
consisting of filling in questionnaires and performing motor function
assessments * take approximately 10 hours, including time to travel. This is a
negligible risk according to the NFU (Nederlandse Federatie van Universitaire
Medische Centra) criteria for human research.