Apomorphine in Parkinson's Disease Patients With Visual Hallucinations
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Apomorphine
Continuous subcutaneous infusion of apomorphine during waking day
Other Names:
|
| Placebo Comparator: 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. |
Drug: Placebo
Continuous subcutaneous infusion of placebo during waking day
|
Outcome Measures
Primary Outcome Measures
- Clinical Global Impression of Severity [Four weeks]
Clinical Global Impression of Severity questionnaire
Secondary Outcome Measures
- 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
- 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
- Apathy [Four weeks]
Apathy Scale
- Quality of Life [Four weeks]
Parkinson's Disease Questionnaire (shortened version)
Other Outcome Measures
- Blood pressure [Four weeks]
Orthostatic blood pressure measurement
- Occurrence of adverse events [Four weeks]
Occurrence of adverse events
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Neurology | Groningen | Netherlands | 9713GZ |
Sponsors and Collaborators
- University Medical Center Groningen
Investigators
- Principal Investigator: Teus van Laar, MD PhD, University Medical Center Groningen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NL55949