Apomorphine in Parkinson's Disease Patients With Visual Hallucinations

Parkinson's Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02702076
• Other study ID #: NL55949
• Status: Recruiting
• Phase: Phase 2
• First received: March 2, 2016
• Last updated: May 1, 2017
• Start date: May 2017
• Est. completion date: December 2017

Study information

• Verified date: May 2017
• Source: University Medical Center Groningen
• Contact: Robbert Borgemeester, MD
• Phone: +31 50 3611519
• Email: r.w.k.borgemeester[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hallucinations
• Hallucinations, Visual
• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Apomorphine
Continuous subcutaneous infusion of apomorphine during waking day
• Placebo
Continuous subcutaneous infusion of placebo during waking day

Locations

Country	Name	City	State
Netherlands	Department of Neurology	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

References & Publications (10)

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. — View Citation

Ellis C, Lemmens G, Parkes JD, Abbott RJ, Pye IF, Leigh PN, Chaudhuri KR. Use of apomorphine in parkinsonian patients with neuropsychiatric complications to oral treatment. Parkinsonism Relat Disord. 1997 Apr;3(2):103-7. — View Citation

Fénelon G, Alves G. Epidemiology of psychosis in Parkinson's disease. J Neurol Sci. 2010 Feb 15;289(1-2):12-7. doi: 10.1016/j.jns.2009.08.014. Epub 2009 Sep 8. Review. — View Citation

Gallagher DA, Parkkinen L, O'Sullivan SS, Spratt A, Shah A, Davey CC, Bremner FD, Revesz T, Williams DR, Lees AJ, Schrag A. Testing an aetiological model of visual hallucinations in Parkinson's disease. Brain. 2011 Nov;134(Pt 11):3299-309. doi: 10.1093/br — View Citation

García Ruiz PJ, Sesar Ignacio A, Ares Pensado B, Castro García A, Alonso Frech F, Alvarez López M, Arbelo González J, Baiges Octavio J, Burguera Hernández JA, Calopa Garriga M, Campos Blanco D, Castaño García B, Carballo Cordero M, Chacón Peña J, Espino I — View Citation

Goetz CG, Ouyang B, Negron A, Stebbins GT. Hallucinations and sleep disorders in PD: ten-year prospective longitudinal study. Neurology. 2010 Nov 16;75(20):1773-9. doi: 10.1212/WNL.0b013e3181fd6158. Epub 2010 Oct 20. — View Citation

Martinez-Martin P, Reddy P, Antonini A, Henriksen T, Katzenschlager R, Odin P, Todorova A, Naidu Y, Tluk S, Chandiramani C, Martin A, Chaudhuri KR. Chronic subcutaneous infusion therapy with apomorphine in advanced Parkinson's disease compared to conventi — View Citation

Martinez-Martin P, Reddy P, Katzenschlager R, Antonini A, Todorova A, Odin P, Henriksen T, Martin A, Calandrella D, Rizos A, Bryndum N, Glad A, Dafsari HS, Timmermann L, Ebersbach G, Kramberger MG, Samuel M, Wenzel K, Tomantschger V, Storch A, Reichmann H — View Citation

Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015 Oct — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood pressure	Orthostatic blood pressure measurement	Four weeks
Other	Occurrence of adverse events	Occurrence of adverse events	Four weeks
Primary	Clinical Global Impression of Severity	Clinical Global Impression of Severity questionnaire	Four weeks
Secondary	Clinical Global Impression of Improvement	Clinical Global Impression of Improvement questionnaire	Four weeks
Secondary	Cognition	Montreal Cognitive Assessment	Four weeks
Secondary	Depression	Hamilton Anxiety and Depression Scale	Four weeks
Secondary	Anxiety	Hamilton Anxiety and Depression Scale	Four weeks
Secondary	Motor symptoms	Part III of Movement Disorders Society - Unified Parkinson's Disease Rating Scale	Four weeks
Secondary	Motor complications	Part IV of Movement Disorders Society - Unified Parkinson's Disease Rating Scale	Four weeks
Secondary	Sleeping problems	Parkinson's Disease Sleep Scale	Four weeks
Secondary	Neuropsychiatric symptoms	Neuropsychiatric Inventory - Questionnaire	Four weeks
Secondary	Visual Hallucinations	Dutch Visual Hallucinations Questionnaire	Four weeks
Secondary	Attention	Reaction Time Task	Four weeks
Secondary	Visual perception	Visual Object and Space Perception battery	Four weeks
Secondary	Apathy	Apathy Scale	Four weeks
Secondary	Quality of Life	Parkinson's Disease Questionnaire (shortened version)	Four weeks