Cholinesterase Inhibitors to Slow Progression of Visual Hallucinations in Parkinson&Apos;s Disease
Status:
Terminated
Trial end date:
2018-09-01
Target enrollment:
Participant gender:
Summary
Rationale: Visual hallucinations (VH) are the most common non-motor symptoms in Parkinson's
disease (PD). As an independent predictor for cognitive decline and nursing home placement
they form an important disability milestone in the course of PD. According to current
clinical guidelines minor VH do not require treatment per se. But as minor VH precede the
stage of major VH without insight and PD associated psychosis (PDP) they offer an opportunity
for early intervention. Neuroleptic drugs delay the transition into PDP but are unsuitable
for early treatment of VH due to their side effects. We hypothesize that cholinesterase
inhibitors (ChEI) are a well-tolerated alternative for the early treatment of minor VH to
delay the progression to PDP, and that brain network analysis is suitable to predict
treatment response.
Objective: Investigate whether early treatment with ChEI delays the progression of minor VH
to major VH without insight or PDP. In addition, we will measure motor control, psychotic
symptoms, cognitive impairment, mood disorders, daytime sleepiness, adverse events and
compliance, disability, caregiver burden and care use. We assess the cost-effectiveness of
early chronic treatment of VH with ChEI. Finally, we analyse changes of functional brain
networks before and during treatment.
Study design: A randomized, double blind, placebo-controlled, multi-center trial with an
economic evaluation.
Study population: 168 patients with PD and VH after fulfilling the in-and exclusion criteria.
Intervention: Rivastigmine capsule 6 mg BID or placebo BID for 24 months.
Main study parameters/endpoints: The primary outcome measure is the median time until PD
patients with minor VH progress to major VH without insight. The clinical endpoint is defined
as the start with antipsychotic treatment. Secondary outcome measures are changes in motor
control, psychotic symptoms, cognitive impairment, mood disorders, daytime sleepiness,
cholinergic deficiency, the number of adverse events, compliance, disability and caregiver
burden. The median time until PD patients with minor VH progress to PD dementia is measured
by means of changes in cognitive function. The secondary neurophysiological outcome measures
are peak frequency, functional connectivity, topological network organisation and the
direction of information flow. All relevant costs will be measured and valued.
Nature and extent of the burden and risks associated with participation, benefit and group
relatedness: The burden of participation consists of a total of 5 clinical visits (every 6
months), 5 telephone interviews on adverse events during the escalation phase and 9
questionnaires on health related costs (every 3 months). In a subgroup 3 additional visits
for EEG recording are needed. There is a risk for adverse reactions with rivastigmine
treatment; the most common are nausea and vomiting.
Phase:
Phase 4
Details
Lead Sponsor:
VU University Medical Center
Collaborators:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Atrium Medical Center International Parkinson Fonds Germany GmbH Leiden University Medical Center University Medical Center Groningen University Medical Center Nijmegen ZonMw: The Netherlands Organisation for Health Research and Development