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Parkinson's Disease | Cholinesterase Inhibitors to Slow Progression of Visual Hallucinations in Parkinsons Disease

Parkinson's Disease research study

What is the primary objective of this study?

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.

Who is eligible to participate?

Inclusion Criteria: - idiopathic PD with bradykinesia and at least two of the following signs; resting tremor, rigidity, and asymmetry (in accordance with clinical diagnostic criteria of the UK PD Society Brain Bank); - the presence of minor VH for at least 4 weeks, defined by a score of 1 or 2 on the hallucinations item of the Unified Parkinson's Disease rating Scale (UPDRS)1-MDS; - age 40 years and over. Exclusion Criteria: - Parkinson's Disease Psychosis, defined as the need for antipsychotic drug treatment in the opinion of the treating neurologist; - Parkinson's Disease Dementia, defined by a score < 24 on the Mini Mental State Examination (MMSE); - current delirium (caused by infection or metabolic disturbance); - current treatment with amantadine (Symmetrel) or anti-cholinergics, such as trihexyfenidyl (Artane) or biperideen (Akineton); - current or recent (<6 months) treatment with Cholinesterase inhibitor, such as rivastigmine (Exelon) or galantamine (Reminyl); - recent (<1 month) change in dopaminergic therapy; - history of psychosis or severe ophtalmologic disease (e.g. Charles Bonnet syndrome); - permanent stay in a nursing home; - no informed consent.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Parkinson's Disease

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:RivastigmineCapsule. Dose 3,0 - 6,0 mg BID

Drug:Placebo (for rivastigmine)Capsule. Dose 3,0 - 6,0 mg BID

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Placeboplacebo capsule for oral use 6,0 mg BID during 24 months of follow-up

Rivastigminerivastigmine capsule for oral use 6,0 mg BID during 24 months of follow-up

Study Status

Recruiting

Start Date: November 2013

Completed Date: December 2022

Phase: Phase 4

Type: Interventional

Design:

Primary Outcome: time to start with antipsychotic treatment for visual hallucinations

Secondary Outcome: motor control

Study sponsors, principal investigator, and references

Principal Investigator: Elisabeth Foncke, Dr.

Lead Sponsor: VU University Medical Center

Collaborator: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

More information:https://clinicaltrials.gov/show/NCT01856738

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