Apomorphine in Parkinson's Disease Patients With Visual Hallucinations

NCT ID: NCT02702076

Last Updated: 2017-05-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-31
• Study Completion Date: 2017-12-31

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.

Conditions

Parkinson's Disease; Hallucinations, Visual

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Apomorphine

Intervention Type: DRUG

Continuous subcutaneous infusion of apomorphine during waking day

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Continuous subcutaneous infusion of placebo during waking day

Interventions

Apomorphine

Continuous subcutaneous infusion of apomorphine during waking day

Intervention Type: DRUG

Placebo

Continuous subcutaneous infusion of placebo during waking day

Intervention Type: DRUG

Other Intervention Names

APO-go; N04BC07

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.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Teus van Laar

MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Teus van Laar, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

Department of Neurology

Groningen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Robbert Borgemeester, MD

Role: CONTACT

r.w.k.borgemeester@umcg.nl

+31 50 3611519

Facility Contacts

Robbert Borgemeester, MD

Role: primary

r.w.k.borgemeester@umcg.nl

+31 (0) 50-3611519

References

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.

Reference Type: RESULT

PMID: 19524477 (View on PubMed)

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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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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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Other Identifiers

NL55949

Identifier Type: -

Identifier Source: org_study_id