Apomorphine in Parkinson's Disease Patients With Visual Hallucinations

Phase 2

• Conditions: Parkinson's Disease; Hallucinations, Visual
• Interventions: Drug: Apomorphine; Drug: Placebo

• Registration Number: NCT02702076
• Lead Sponsor: University Medical Center Groningen

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.

Study Timeline

• Study First Submitted: 2016-03-02
• Study First Submitted QC: 2016-03-02
• Study First Posted: 2016-03-08
• Status Verified: 2017-05
• Study Start: 2017-05
• Last Update Submitted: 2017-05-01
• Last Update Posted: 2017-05-03
• Primary Completion: 2017-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 35

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Apomorphine	Apomorphine	This arm will be treated with continuous subcutaneous infusion of apomorphine. The infusion will start with 1 mg/hr during the waking day (approximately 16 hours). The flow rate will be adjusted on a weekly basis, and may be increased with 0.5 to 1.0 mg/hr per discretion of the investigator, aiming at the disappearance of visual hallucinations. The duration of treatment is 4 weeks.
Placebo	Placebo	This arm will be treated with continuous subcutaneous infusion of placebo. The infusion will start with 1 mg/hr during the waking day (approximately 16 hours). The flow rate will be adjusted on a weekly basis, and may be increased with 0.5 to 1.0 mg/hr per discretion of the investigator aiming at the disappearance of visual hallucinations. The duration of treatment is 4 weeks.

Primary Outcome Measures

Name	Time	Method
Clinical Global Impression of Severity	Four weeks	Clinical Global Impression of Severity questionnaire

Secondary Outcome Measures

Name	Time	Method
Clinical Global Impression of Improvement	Four weeks	Clinical Global Impression of Improvement questionnaire
Apathy	Four weeks	Apathy 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
Neuropsychiatric symptoms	Four weeks	Neuropsychiatric Inventory - Questionnaire
Visual perception	Four weeks	Visual Object and Space Perception battery
Cognition	Four weeks	Montreal Cognitive Assessment
Anxiety	Four weeks	Hamilton Anxiety and Depression Scale
Visual Hallucinations	Four weeks	Dutch Visual Hallucinations Questionnaire
Quality of Life	Four weeks	Parkinson's Disease Questionnaire (shortened version)
Depression	Four weeks	Hamilton Anxiety and Depression Scale
Motor symptoms	Four weeks	Part III of Movement Disorders Society - Unified Parkinson's Disease Rating Scale
Attention	Four weeks	Reaction Time Task

Trial Locations

Locations (1)

Department of Neurology; 🇳🇱 Groningen, Netherlands