Cholinesterase Inhibitors to Slow Progression of Visual Hallucinations in Parkinson&Apos;s Disease

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.

Conditions

• Parkinson's Disease

Interventions

DRUG

Rivastigmine

Capsule. Dose 3,0 - 6,0 mg BID

DRUG

Placebo (for rivastigmine)

Capsule. Dose 3,0 - 6,0 mg BID

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  collaborator OTHER

• Atrium Medical Center

  collaborator OTHER

• University Medical Center Groningen

  collaborator OTHER

• Leiden University Medical Center

  collaborator OTHER

• University Medical Center Nijmegen

  collaborator OTHER

• International Parkinson Fonds Germany GmbH

  collaborator INDUSTRY

• ZonMw: The Netherlands Organisation for Health Research and Development

  collaborator OTHER

• Amsterdam UMC, location VUmc

  lead OTHER

Principal Investigators

• Elisabeth Foncke, Dr. · Amsterdam UMC, location VUmc

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

SINGLE_GROUP

Eligibility

Min Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-11-30

Primary Completion

2018-09-30

Completion

2018-09-30

Countries

• Netherlands

Study Locations