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Ambroxol as a Treatment for Parkinson's Disease Dementia

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ClinicalTrials.gov Identifier: NCT02914366
Recruitment Status : Recruiting
First Posted : September 26, 2016
Last Update Posted : March 7, 2017
Sponsor:
Collaborators:
The Weston A. Price Foundation
University of Western Ontario, Canada
London Health Sciences Centre
Information provided by (Responsible Party):
Stephen Pasternak, University of Western Ontario, Canada

Study Description
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Brief Summary:
The present study will test the hypothesis that the medication Ambroxol is safe and well tolerated and will improve cognitive and motor symptoms of Parkinson's Disease Dementia (PDD). Ambroxol has been shown to raise the levels of the enzyme beta-glucocerebrosidase resulting in lower the levels of the protein alpha-synuclein, both of which have been shown to improve cognition in mouse models. This will be a 52 week trial of Ambroxol in 75 patients with PDD. Patients will undergo clinical, neuropsychological and neuroimaging assessment throughout the study to assess changes.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Dementia Drug: Ambroxol Other: Placebo Phase 2

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ambroxol as a Novel Disease Modifying Treatment for Parkinson's Disease Dementia
Study Start Date : November 2015
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Ambroxol high dose (1050 mg)
Participants randomized to the 1050 mg/day group will begin with a dose of 225mg (3 mg/kg/day), increasing bi-weekly by ~3mg/kg to a dose of 1050 mg/day (~l5 mg/kg/day).
 Drug: Ambroxol
Other Name: Mucosolvon
Experimental: Ambroxol low dose (525 mg)
Participants randomized to the 525 mg/day group will begin with a dose of 150 mg/day increasing biweekly by ~1.5mg/kg to a dose of 525 mg/day.
 Drug: Ambroxol
Other Name: Mucosolvon
Placebo Comparator: Placebo
Participants receive capsules visually identical to the experimental groups but without active ingredients.
 Other: Placebo


Outcome Measures
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Primary Outcome Measures :
  1. Changes in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) [ Time Frame: baseline, week 26, and week 52 ]
    This 70-point test examines language, recall, word finding, comprehension, naming, drawing, praxis, orientation, and word recognition. Although designed for Alzheimer's disease where it is considered a gold standard, the ADAS-Cog has been used effectively in many clinical trials of PDD including large randomized trials. This scale has been recommended for the assessment of Parkinson's dementia in "Diagnostic Procedures for Parkinson's Disease Dementia: Recommendations from the Movement Disorder Society Task Force"

  2. Changes in the ADCS-Clinician's Global Impression of Change (CGIC) [ Time Frame: baseline, week 26, and week 52 ]
    This is a 7-point scale for rating patient function in cognition behavior and activities of daily living, and this test is standard in clinical trials in Alzheimer's disease and has been useful in trials with PDD.


Secondary Outcome Measures :
  1. Changes in the Montreal Cognitive Assessment [ Time Frame: baseline, week 26, and week 52 ]
  2. Changes in the Clinical Dementia Rating Scale (CDR) [ Time Frame: baseline, week 26, and week 52 ]
  3. Changes in the Trail Making Test (TRAILS) [ Time Frame: baseline, week 26, and week 52 ]
  4. Changes in the Parkinson's Disease-Cognitive Rating Scale (PD-CRS) [ Time Frame: baseline, week 26, and week 52 ]
  5. Changes in the Stroop Test [ Time Frame: baseline, week 26, and week 52 ]
  6. Changes in the Unified Parkinson's disease Rating Scale motor subsection (UPDRS-III) [ Time Frame: baseline, week 26, and week 52 ]
  7. Changes in the Purdue Pegboard [ Time Frame: baseline, week 26, and week 52 ]
  8. Changes in the Timed Up and Go [ Time Frame: baseline, week 26, and week 52 ]
  9. Change in Quantitative Movement Testing [ Time Frame: baseline, week 26, and week 52 ]
    gait assessment on electronic mat (Zeno Walkway System)

  10. Changes in Cerebrospinal Fluid (CSF) biomarkers [ Time Frame: baseline, week 12, and week 52 ]
    levels of α-synuclein (pg/ml), Tau (pg/ml), phospho-Tau (pg/ml) and beta amyloid-42 (pg/ml)

  11. Changes in Magnetic Resonance Imaging (MRI) [ Time Frame: baseline and week 52 ]
    brain ventricle volume (cm3) and hippocampal atrophy (cm3)

  12. Changes in the Mini-Mental State Examination [ Time Frame: screening, baseline, week 4, week 6, week 12, week 18, week 26, week 34, week 42, week 52 ]
  13. Changes in GCAse in lymphocytes [ Time Frame: baseline, week 2, week 4, week 6, week 8, week 12, week 18, week 26, week 34, week 42, week 52 ]
    from blood sample

  14. Changes in Plasma Ambroxol levels [ Time Frame: baseline, week 2, week 4, week 6, week 8, week 12, week 18, week 26, week 34, week 42, week 52 ]
    from blood sample


Eligibility Criteria
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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >50,
  2. Mild to Moderate Dementia (established by an upper cut off of a Montreal Cognitive Assessment score of 24 or below, and the lower bound by a Mini Mental State Exam of 16 or greater),
  3. Parkinson's Disease (Hoehn & Yahr stage 2 - 3.5) clearly established more than 1 year before the onset of dementia
  4. Patients must have a responsible caregiver = 4 days/wk
  5. Must be on stable doses of medications for Parkinson's disease mood and cognition (Cholinesterase Inhibitor) for at least 3 months prior to the study.

Exclusion Criteria:

  1. Evidence of clinically significant stroke or other neurological condition
  2. any other serious underlying condition (i.e. cancer or unstable cardiac disease etc.
  3. contraindication to MRI (e.g. presence of metal fragments in head or eye, implanted electrical devices), or conductive implants, or devices (e.g. pacemakers, neurostimulators) or participant unwilling .
Contacts and Locations
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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): NCT02914366


Contacts
Contact: Stephen Pasternak, M.D., Ph.D. +1 519-646-6000 ext 66032 spasternak@robarts.ca
Contact: Carolina Silveira, Ph.D +1 519-656-6100 ext 42367 Carolina.Silveira@sjhc.london.ca

Locations
Canada, Ontario
Parkwood Institute Recruiting
London, Ontario, Canada, N6C 0A7
Contact: Carolina Silveira, Ph.D    519-646-6100 ext 42367    Carolina.Silveira@sjhc.london.on.ca   
Contact: Tommy Li, MSc    519-646-6100 ext 42711    Zhonghan.Li@sjhc.london.on.ca   
Sponsors and Collaborators
Lawson Health Research Institute
The Weston A. Price Foundation
University of Western Ontario, Canada
London Health Sciences Centre
More Information
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Publications:
Narita A, Kubota N, Takayama R, Takahashi Y, Maegaki Y, Suzuki Y, & Ohno K. Chaperone therapy for neuronopathic Gaucher disease. Molecular Genetics and Metabolism, 108(2): S69, 2013.
Narita A, Zhuo L, Higaki K, Togawa M, Maegaki Y, Nanba E, Suzuko Y, Ohno K: Chemical chaperone therapy for neuropathic Gaucher disease. In 12th International Child Neurology Congress and the 11th Asian and Oceanian Congress of Child Neurology Brisbane. QLD Australia: Developmental Medicine and Child Neurology (54): 50-51, 2012.

Responsible Party: Stephen Pasternak, M.D., Ph.D., University of Western Ontario, Canada
ClinicalTrials.gov Identifier: NCT02914366     History of Changes
Other Study ID Numbers: R15-006
105234 ( Other Identifier: Western University Health Science Research Ethics Board (HSREB) )
181033 ( Other Identifier: Health Canada )
First Posted: September 26, 2016    Key Record Dates
Last Update Posted: March 7, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Peer reviewed publication | Presentation

Keywords provided by Stephen Pasternak, University of Western Ontario, Canada:
Ambroxol
Dementia
Parkinson's disease
 Disease modifying treatment
Pharmacological Chaperone
GBA1

Additional relevant MeSH terms:
Parkinson Disease
Dementia
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Movement Disorders
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Ambroxol
Expectorants
Respiratory System Agents