Hallucinations, Visual, Parkinson's Disease
Conditions
Keywords
Apomorphine
Brief summary
This randomised, double-blind, placebo-controlled trial will evaluate the efficacy of continuous apomorphine infusion compared to placebo in PD patients with visual hallucinations, inadequately controlled with clozapine and cholinesterase inhibitors.
Detailed description
Introduction Visual hallucinations occur frequently in Parkinson's disease (PD). The prevalence of visual hallucinations ranges from 22 to 38%, increasing after long-term follow-up to more than 60%. Risk factors for visual hallucinations are age, disease duration, and cognitive impairment. The treatment of visual hallucinations is cumbersome and options are limited. Only clozapine has been proven to be efficacious without deteriorating the motor symptoms of PD. Instead of oral dopamine agonists and rotigotine, continuous infusion of apomorphine is well-tolerated in PD patients with cognitive impairments and/or visual hallucinations. Even beneficial effect of apomorphine on visual hallucinations are suggested, however there is lack of a randomized controlled trial. The purpose of this randomised, double-blind, placebo-controlled trial is to evaluate the efficacy of continuous apomorphine infusion compared to placebo in PD patients with visual hallucinations, inadequately controlled with clozapine and cholinesterase inhibitors.
Interventions
DRUGApomorphine
Continuous subcutaneous infusion of apomorphine during waking day
DRUGPlacebo
Continuous subcutaneous infusion of placebo during waking day
Sponsors
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female and male subjects aged ≥30; * Diagnosis of established PD, defined by the Movement Disorders Society PD criteria (Postuma et al., 2015); * Presence of visual severe hallucinations defined as more than 3 times a week (van Laar et al., 2010); * Visual hallucinations must have developed after PD diagnosis; * Visual hallucinations must have been optimally treated with reduction of dopamine agonists if possible, and prescription of clozapine and/or cholinesterase inhibitors if needed; * Female subjects must complaint with a highly effective contraceptive method (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method) during the study, if sexually active; * Subjects should be able and capable of adhering to the protocol, visit schedules, and medication intake according to the judgement of the investigator.
Exclusion criteria
* Symptomatic, clinically relevant and medically uncontrolled orthostatic hypotension; * Patients with a prolonged QT interval corrected for heart rate according to Bazett's formula (QTc) of \>450 ms for male and \>470 ms for female at screening, or history of a long QT syndrome; * PD medication change (i.e., dopamine-agonists, amantadine, monoamine oxidase (MAO)-B inhibitors, anticholinergics and cholinesterase inhibitors) in last month prior to initiation (van Laar et al., 2010); * Active psychosis or a history of significant psychosis; * Any medical condition that is likely to interfere with an adequate participation in the study including e.g. current diagnosis of unstable epilepsy, clinically relevant cardiac dysfunction and/or myocardial infarction or stroke within the last 12 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Severity | Four weeks | Clinical Global Impression of Severity questionnaire |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Improvement | Four weeks | Clinical Global Impression of Improvement questionnaire |
| Cognition | Four weeks | Montreal Cognitive Assessment |
| Depression | Four weeks | Hamilton Anxiety and Depression Scale |
| Anxiety | Four weeks | Hamilton Anxiety and Depression Scale |
| Motor symptoms | Four weeks | Part III of Movement Disorders Society - Unified Parkinson's Disease Rating Scale |
| Motor complications | Four weeks | Part IV of Movement Disorders Society - Unified Parkinson's Disease Rating Scale |
| Sleeping problems | Four weeks | Parkinson's Disease Sleep Scale |
| Apathy | Four weeks | Apathy Scale |
| Quality of Life | Four weeks | Parkinson's Disease Questionnaire (shortened version) |
| Neuropsychiatric symptoms | Four weeks | Neuropsychiatric Inventory - Questionnaire |
| Visual Hallucinations | Four weeks | Dutch Visual Hallucinations Questionnaire |
| Attention | Four weeks | Reaction Time Task |
| Visual perception | Four weeks | Visual Object and Space Perception battery |
Other
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure | Four weeks | Orthostatic blood pressure measurement |
| Occurrence of adverse events | Four weeks | Occurrence of adverse events |
Countries
Netherlands
Contacts
Primary ContactRobbert Borgemeester, MD
Outcome results
None listed