Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Apomorphine in Parkinson's Disease Patients With Visual Hallucinations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02702076
Recruitment Status : Unknown
Verified May 2017 by Teus van Laar, University Medical Center Groningen.
Recruitment status was:  Recruiting
First Posted : March 8, 2016
Last Update Posted : May 3, 2017
Sponsor:
Information provided by (Responsible Party):
Teus van Laar, 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.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Hallucinations, Visual Drug: Apomorphine Drug: Placebo 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Estimated Study Start Date : May 2017
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine


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:
  • APO-go
  • N04BC07

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




Primary Outcome Measures :
  1. Clinical Global Impression of Severity [ Time Frame: Four weeks ]
    Clinical Global Impression of Severity questionnaire


Secondary Outcome Measures :
  1. Clinical Global Impression of Improvement [ Time Frame: Four weeks ]
    Clinical Global Impression of Improvement questionnaire

  2. Cognition [ Time Frame: Four weeks ]
    Montreal Cognitive Assessment

  3. Depression [ Time Frame: Four weeks ]
    Hamilton Anxiety and Depression Scale

  4. Anxiety [ Time Frame: Four weeks ]
    Hamilton Anxiety and Depression Scale

  5. Motor symptoms [ Time Frame: Four weeks ]
    Part III of Movement Disorders Society - Unified Parkinson's Disease Rating Scale

  6. Motor complications [ Time Frame: Four weeks ]
    Part IV of Movement Disorders Society - Unified Parkinson's Disease Rating Scale

  7. Sleeping problems [ Time Frame: Four weeks ]
    Parkinson's Disease Sleep Scale

  8. Neuropsychiatric symptoms [ Time Frame: Four weeks ]
    Neuropsychiatric Inventory - Questionnaire

  9. Visual Hallucinations [ Time Frame: Four weeks ]
    Dutch Visual Hallucinations Questionnaire

  10. Attention [ Time Frame: Four weeks ]
    Reaction Time Task

  11. Visual perception [ Time Frame: Four weeks ]
    Visual Object and Space Perception battery

  12. Apathy [ Time Frame: Four weeks ]
    Apathy Scale

  13. Quality of Life [ Time Frame: Four weeks ]
    Parkinson's Disease Questionnaire (shortened version)


Other Outcome Measures:
  1. Blood pressure [ Time Frame: Four weeks ]
    Orthostatic blood pressure measurement

  2. Occurrence of adverse events [ Time Frame: Four weeks ]
    Occurrence of adverse events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02702076


Contacts
Layout table for location contacts
Contact: Robbert Borgemeester, MD +31 50 3611519 r.w.k.borgemeester@umcg.nl

Locations
Layout table for location information
Netherlands
Department of Neurology Recruiting
Groningen, Netherlands, 9713GZ
Contact: Robbert Borgemeester, MD    +31 (0) 50-3611519    r.w.k.borgemeester@umcg.nl   
Sub-Investigator: Robbert Borgemeester, MD         
Principal Investigator: Teus van Laar, MD PhD         
Sponsors and Collaborators
University Medical Center Groningen
Investigators
Layout table for investigator information
Principal Investigator: Teus van Laar, MD PhD University Medical Center Groningen
Publications of Results:
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 Ibáñez A, Gorospe Onisalde A, Giménez-Roldán S, Granés Ibáñez P, Hernández Vara J, Ibáñez Alonso R, Jiménez Jiménez FJ, Krupinski J, Kulisevsky Bojarsky J, Legarda Ramírez I, Lezcano García E, Martínez-Castrillo JC, Mateo González D, Miquel Rodríguez F, Mir P, Muñoz Fargas E, Obeso Inchausti J, Olivares Romero J, Olivé Plana J, Otermin Vallejo P, Pascual Sedano B, Pérez de Colosía Rama V, Pérez López-Fraile I, Planas Comes A, Puente Periz V, Rodríguez Oroz MC, Sevillano García D, Solís Pérez P, Suárez Muñoz J, Vaamonde Gamo J, Valero Merino C, Valldeoriola Serra F, Velázquez Pérez JM, Yáñez Baña 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.

Layout table for additonal information
Responsible Party: Teus van Laar, MD PhD, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT02702076    
Other Study ID Numbers: NL55949
First Posted: March 8, 2016    Key Record Dates
Last Update Posted: May 3, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Teus van Laar, University Medical Center Groningen:
Apomorphine
Additional relevant MeSH terms:
Layout table for MeSH terms
Parkinson Disease
Hallucinations
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Perceptual Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Apomorphine
Emetics
Physiological Effects of Drugs
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action