Clinical trial NCT02702076: Apomorphine in Parkinson's Disease Patients With Visual Hallucinations
Official title: Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Continuous Subcutaneous Infusion in Parkinson's Disease Patients With Refractory Visual Hallucinations
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Parkinson's Disease
Hallucinations, Visual
Keywords: Apomorphine
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2016-03-08
Enrollment: 35
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Global Impression of Severity
timeFrame: Four weeks
Secondary outcomes:
measure: Clinical Global Impression of Improvement
timeFrame: Four weeks
measure: Cognition
timeFrame: Four weeks
measure: Depression
timeFrame: Four weeks
measure: Anxiety
timeFrame: Four weeks
measure: Motor symptoms
timeFrame: Four weeks
measure: Motor complications
timeFrame: Four weeks
measure: Sleeping problems
timeFrame: Four weeks
measure: Neuropsychiatric symptoms
timeFrame: Four weeks
measure: Visual Hallucinations
timeFrame: Four weeks
measure: Attention
timeFrame: Four weeks
measure: Visual perception
timeFrame: Four weeks
measure: Apathy
timeFrame: Four weeks
measure: Quality of Life
timeFrame: Four weeks
Other outcomes:
measure: Blood pressure
timeFrame: Four weeks
measure: Occurrence of adverse events
timeFrame: Four weeks
Locations:
city: Groningen
country: Netherlands
facility: Department of Neurology
Study officials:
affiliation: University Medical Center Groningen
name: Teus van Laar, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Laar T, Postma AG, Drent M. Continuous subcutaneous infusion of apomorphine can be used safely in patients with Parkinson's disease and pre-existing visual hallucinations. Parkinsonism Relat Disord. 2010 Jan;16(1):71-2. doi: 10.1016/j.parkreldis.2009.05.006. Epub 2009 Jun 12. No abstract available.
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citation: Borgemeester RW, Drent M, van Laar T. Motor and non-motor outcomes of continuous apomorphine infusion in 125 Parkinson's disease patients. Parkinsonism Relat Disord. 2016 Feb;23:17-22. doi: 10.1016/j.parkreldis.2015.11.013. Epub 2015 Nov 22.
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