Apomorphine in Parkinson's Disease Patients With Visual Hallucinations

NCT02702076 | Unknown Phase 2

• 1 other identifier: NL55949
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease; Hallucinations, Visual

Keywords

Apomorphine

Outcome Measures

Primary Outcomes (1)

• Clinical Global Impression of Severity

  Clinical Global Impression of Severity questionnaire

  Four weeks

Secondary Outcomes (13)

• Clinical Global Impression of Improvement

  Four weeks

• Cognition

  Four weeks

• Depression

  Four weeks

• Anxiety

  Four weeks

• Motor symptoms

  Four weeks

Other Outcomes (2)

• Blood pressure

  Four weeks

• Occurrence of adverse events

  Four weeks

Study Arms (2)

Apomorphine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Apomorphine DRUG

Continuous subcutaneous infusion of apomorphine during waking day

Also known as: APO-go, N04BC07

Apomorphine

Placebo DRUG

Continuous subcutaneous infusion of placebo during waking day

Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

Department of Neurology

Groningen, 9713GZ, Netherlands

RECRUITING

Related Publications (10)

• 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.

  PMID: 19524477 RESULT

• 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;30(12):1591-601. doi: 10.1002/mds.26424.

  PMID: 26474316 RESULT

• Fenelon 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.

  PMID: 19740486 RESULT

• 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.

  PMID: 20962287 RESULT

• 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/brain/awr225. Epub 2011 Sep 15.

  PMID: 21921019 RESULT

• 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.

  PMID: 26709292 RESULT

• Garcia Ruiz PJ, Sesar Ignacio A, Ares Pensado B, Castro Garcia A, Alonso Frech F, Alvarez Lopez M, Arbelo Gonzalez J, Baiges Octavio J, Burguera Hernandez JA, Calopa Garriga M, Campos Blanco D, Castano Garcia B, Carballo Cordero M, Chacon Pena J, Espino Ibanez A, Gorospe Onisalde A, Gimenez-Roldan S, Granes Ibanez P, Hernandez Vara J, Ibanez Alonso R, Jimenez Jimenez FJ, Krupinski J, Kulisevsky Bojarsky J, Legarda Ramirez I, Lezcano Garcia E, Martinez-Castrillo JC, Mateo Gonzalez D, Miquel Rodriguez F, Mir P, Munoz Fargas E, Obeso Inchausti J, Olivares Romero J, Olive Plana J, Otermin Vallejo P, Pascual Sedano B, Perez de Colosia Rama V, Perez Lopez-Fraile I, Planas Comes A, Puente Periz V, Rodriguez Oroz MC, Sevillano Garcia D, Solis Perez P, Suarez Munoz J, Vaamonde Gamo J, Valero Merino C, Valldeoriola Serra F, Velazquez Perez JM, Yanez Bana R, Zamarbide Capdepon I. Efficacy of long-term continuous subcutaneous apomorphine infusion in advanced Parkinson's disease with motor fluctuations: a multicenter study. Mov Disord. 2008 Jun 15;23(8):1130-6. doi: 10.1002/mds.22063.

  PMID: 18442107 RESULT

• 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 conventional therapy: a real life study of non motor effect. J Parkinsons Dis. 2011;1(2):197-203. doi: 10.3233/JPD-2011-11037.

  PMID: 23934921 RESULT

• 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, Pirtosek Z, Trost M, Svenningsson P, Palhagen S, Volkmann J, Chaudhuri KR. EuroInf: a multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson's disease. Mov Disord. 2015 Apr;30(4):510-6. doi: 10.1002/mds.26067. Epub 2014 Nov 10.

  PMID: 25382161 RESULT

• 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. doi: 10.1016/s1353-8020(97)00009-6.

  PMID: 18591063 RESULT

MeSH Terms

Conditions

Parkinson Disease; Hallucinations

Interventions

Apomorphine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aporphines; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Study Officials

• Teus van Laar, MD PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robbert Borgemeester, MD

CONTACT

+31 50 3611519; r.w.k.borgemeester@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: March 2, 2016
• First Posted: March 8, 2016
• Study Start: May 1, 2017
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: May 3, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)