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

Ambroxol as a Novel Disease Modifying Treatment for Lewy Body Dementia

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04405596
Recruitment Status : Not yet recruiting
First Posted : May 28, 2020
Last Update Posted : May 29, 2020
Sponsor:
Information provided by (Responsible Party):
Stephen Pasternak, Lawson Health Research Institute

Brief Summary:

This is a randomized, placebo-controlled, double-blind study investigating whether the medication Ambroxol is safe,effectiveness and well tolerated for the treatment of Lewy Body Dementia (LBD). Currently the main treatments for patients with LBD target symptom management. However, none of the medications treat the underlying cause of the disease, which includes the accumulation of protein in the brain. Therefore, even if patients respond well to symptomatic treatment, they continue to deteriorate. Therefore, the purpose of the current study is to make sure Ambroxol is safe to take long term and to test the effects of Ambroxol in treating the cognitive impairments associated with LBD by modifying the underlying causes of the disease.

There will be a total of 15 people participating this this study, which will last 52 weeks. Over the study period patients will undergo clinical, neuropsychological and neuroimaging assessment to assess changes.


Condition or disease Intervention/treatment Phase
Lewy Body Disease Drug: Ambroxol Hydrochloride Other: Placebo Phase 1 Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 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 Lewy Body Dementia
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ambroxol
Participants randomized to the 1350 mg/day group will begin with a dose of 450 mg, increasing bi-weekly to a dose of 1350 mg/day.
Drug: Ambroxol Hydrochloride
The treatment regimen consists of a titration phase and a maintenance phase. Participants begin the titration phase (Weeks 1 and 2) taking 6 capsules a day (450mg or 0 mg) divided BID (3 capsules in the morning and 3 capsules in the evening). The first medication dose will be taken at the end of Baseline visit and in the presence of the study Neurologist. Possible side effects will be observed for 30 minutes. Medication dose will increase bi-weekly to 12 capsules on Weeks 3 and 4, and 18 capsules on Weeks 5 and 6 divided BID. At the end of titration (Week 5) participants will have reached a maximum of 1350mg or 0mg per day, depending on group allocation. In the maintenance phase, participants will remain in their maximum dose (1350mg or 0mg) from Week 5 to Week 52 (End of Trial).
Other Name: Mucosolvan

Placebo Comparator: Placebo
Participants receive capsules visually identical to the experimental groups but without active ingredients.
Other: Placebo
The treatment regimen consists of a titration phase and a maintenance phase. Participants begin the titration phase (Weeks 1 and 2) taking 6 capsules a day (450mg or 0 mg) divided BID (3 capsules in the morning and 3 capsules in the evening). The first medication dose will be taken at the end of Baseline visit and in the presence of the study Neurologist. Possible side effects will be observed for 30 minutes. Medication dose will increase bi-weekly to 12 capsules on Weeks 3 and 4, and 18 capsules on Weeks 5 and 6 divided BID. At the end of titration (Week 5) participants will have reached a maximum of 1350mg or 0mg per day, depending on group allocation. In the maintenance phase, participants will remain in their maximum dose (1350mg or 0mg) from Week 5 to Week 52 (End of Trial).




Primary Outcome Measures :
  1. Change in Mini Mental State Examination score from baseline over time [ Time Frame: Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52 ]
    Monitor safety using frequent cognitive evaluations using the mini mental state examination. Lower scores are indicative of worsening cognitive impairment [score range: 0-30]

  2. Change in the incidence, nature and severity of AE's and SAE's from baseline [ Time Frame: Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52 ]
    Change in the number of participants with AE's and SAE's

  3. Change in the number of participants with treatment discontinuations and study discontinuation due to AEs from baseline [ Time Frame: Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52 ]
    Change from baseline in the number of participants with treatment and/or study discontinuation will be used to demonstrate safety and tolerability

  4. Change in the number of participants with electrocardiogram (ECG) abnormalities [ Time Frame: Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52 ]
    Change from baseline in the number of participants with clinically significant ECG abnormalities (QT interval) to demonstrate safety

  5. Change from baseline the number of participants with abnormal changes in hemodynamic values while seated [ Time Frame: Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52 ]
    Changes in hemodynamic values from baseline over time to demonstrate safety

  6. Change from baseline the number of participants with abnormal changes in hemodynamic values while standing [ Time Frame: Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52 ]
    Changes in hemodynamic values from baseline over time to demonstrate safety

  7. Change in blood analyses from baseline over time [ Time Frame: Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52 ]
    Change from baseline in number of participants with abnormal changes in clinical laboratory blood tests from baseline over time for safety

  8. Change in urine analyses from baseline over time [ Time Frame: Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52 ]
    Change from baseline in number of participants with abnormal changes in clinical laboratory urine tests from baseline over time for safety

  9. Change from baseline in plasma concentrations of Ambroxol from blood sample [ Time Frame: Baseline, week 4, week 10, week 26, week 52 ]
    Change in plasma Ambroxol concentrations from blood sample from baseline

  10. Change from baseline in cerebrospinal fluid (CSF) concentrations of Ambroxol at specified time points [ Time Frame: Baseline, week 10, week 52 ]
    Change in Ambroxol concentrations from cerebrospinal fluid sample from baseline

  11. Change from baseline in enzyme β-Glucocerebrosidase (GCase) concentration levels in CSF [ Time Frame: Baseline, week 10, week 52 ]
    Change in GCase concentration in the CSF from baseline

  12. Change from baseline in enzyme β-Glucocerebrosidase (GCase) concentration levels in white blood cells [ Time Frame: Baseline, week 4, week 10, week 26, week 52 ]
    Change in white blood cell GCase concentrations from baseline


Secondary Outcome Measures :
  1. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: Baseline, week 26, and week 52 ]
    Demonstrate the efficacy of Ambroxol in improving, or slowing the progression of cognitive deficits. Lower scores are indicative of worsening cognitive function [score range: 40-160]

  2. Clinician's Global Impression of Change (CGIC) [ Time Frame: Baseline, week 26, and week 52 ]
    Demonstrate the efficacy of Ambroxol in improving, or slowing the progression of cognitive deficits. Patients are assessed as: no change, minimal, moderate and marked worsening, minimal, moderate and marked improvement

  3. Montreal Cognitive Assessment (MoCA) [ Time Frame: Baseline, week 26, and week 52 ]
    Demonstrate the efficacy of Ambroxol in improving, or slowing the progression of cognitive deficits. Lower scores are indicative of worsening cognitive impairment [score range: 0-30]

  4. Trail making test A and B to assess cognitive function [ Time Frame: Baseline, week 26, and week 52 ]
    Demonstrate the efficacy of Ambroxol in improving, or slowing the progression of cognitive deficits: Higher times to complete are indicative of worsening cognitive function [Max time: 300 seconds]

  5. Parkinson's disease - Cognitive rating scale to assess cognitive function [ Time Frame: Baseline, week 26, and week 52 ]
    Demonstrate the efficacy of Ambroxol in improving, or slowing the progression of cognitive deficits. Lower scores are indicative of higher cognitive dysfunction [Score range: 0-134]

  6. Change in regional brain magnetic resonance imaging atrophy measures [ Time Frame: Baseline, week 52 ]
    Change in hippocampal atrophy (cm3)

  7. Change in global brain magnetic resonance imaging atrophy measures [ Time Frame: Baseline, week 52 ]
    Change in brain ventricle volume (cm3)

  8. Change in plasma biomarkers [ Time Frame: Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52 ]
    Change in levels of plasma biomarkers: α-synuclein (pg/ml), Tau (pg/ml), phospho-Tau (pg/ml) and beta amyloid-42 (pg/ml) in plasma

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

  10. Neuropsychological Inventory (NPI) [ Time Frame: Baseline, week 26, and week 52 ]
    Demonstrate change or slowed progression in standard tests of mood and neuropsychiatric symptoms. Assesses frequency and severity of neuropsychological symptoms with higher scores indicative of more symptoms, higher frequency and more severe. [Score range: 0-144]

  11. Geriatric Depression Scale [ Time Frame: Baseline, week 26, and week 52 ]
    Demonstrate change or slowed progression in standard tests of mood and neuropsychiatric symptoms: Higher scores indicate more severe depression [score range: 0-15]

  12. The Motor subscale of Unified Parkinson's Disease Rating Scale (UPDRS-III) [ Time Frame: Baseline, week 26, and week 52 ]
    Demonstrate change or slowed progression in tests of motor function/Parkinsonism: Higher scores indicate more dysfunction [score range: 0-108]

  13. Timed Up and Go [ Time Frame: Baseline, week 26, and week 52 ]
    Demonstrate change or slowed progression in tests of motor function/Parkinsonism. Higher times indicate slower movement and more motor impairment



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

Inclusion Criteria:

  1. Probable diagnosis of Lewy Body Dementia
  2. Age greater than 50 years old
  3. Montreal Cognitive Assessment (MoCA) score: 24-18
  4. Patients must have a responsible caregiver = 4days/week
  5. Must be on a stable dose of medications for parkinsonism (levodopa, dopaminergic agonist) and cognition (cholinesterase inhibitors) and psychiatric (i.e. antidepressants, antipsychotic) for at least 3 months prior to the study

Exclusion Criteria:

  1. Evidence of stroke or other neurological condition
  2. Any other serious underlying condition or brain disorder that can account in part of in full for the clinical presentation (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 (pacemakers, neurostimulators).
  4. Unable to undergo DAT-scan
  5. Depression that is, in the opinion of the investigator, significant enough to interfere with neuropsychology and safety assessments
  6. Females who are pregnant or breastfeeding, or planning to conceive within the study period
  7. Concurrent treatment with oral anticoagulants (including Vitamin K agonists and Novel Oral Anticoagulants (NOACs)) within 4 weeks of screening or anticipated during the 52 week double-blind and open label periods. Specifically, Apixaban, Dabigatran, Edoxaban, Fondaparinux, Rivaroxaban, and Warfarin are prohibited concomitant medications. Exceptions: antiplatelet agents such as Aspirin, Clopidogrel, and Aggrenox.

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): NCT04405596


Contacts
Layout table for location contacts
Contact: Stephen Pasternak, MD, PhD 519-646-6000 ext 66032 spasternak@robarts.cs
Contact: Carolina Silveira, PhD 519-646-6100 ext 42367 Carolina.Silveira@sjhc.london.ca

Locations
Layout table for location information
Canada, Ontario
Parkwood Institute
London, Ontario, Canada, N6C0A7
Contact: Carolina Silveira, PhD    519-646-6100 ext 42367    Carolina.Silveira@sjhc.london.ca   
Sponsors and Collaborators
Lawson Health Research Institute
Publications:
Nalls MA, Duran R, Lopez G, Kurzawa-Akanbi M, McKeith IG, Chinnery PF, Morris CM, Theuns J, Crosiers D, Cras P, Engelborghs S, De Deyn PP, Van Broeckhoven C, Mann DM, Snowden J, Pickering-Brown S, Halliwell N, Davidson Y, Gibbons L, Harris J, Sheerin UM, Bras J, Hardy J, Clark L, Marder K, Honig LS, Berg D, Maetzler W, Brockmann K, Gasser T, Novellino F, Quattrone A, Annesi G, De Marco EV, Rogaeva E, Masellis M, Black SE, Bilbao JM, Foroud T, Ghetti B, Nichols WC, Pankratz N, Halliday G, Lesage S, Klebe S, Durr A, Duyckaerts C, Brice A, Giasson BI, Trojanowski JQ, Hurtig HI, Tayebi N, Landazabal C, Knight MA, Keller M, Singleton AB, Wolfsberg TG, Sidransky E. A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies. JAMA Neurol. 2013 Jun;70(6):727-35. doi: 10.1001/jamaneurol.2013.1925.
Low, P., & Benarroch, E. (2008). Clinical Autonomic Disorders. (P. Low & E. Benarroch, Eds.) (Third). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins
Narita, A., Zhou, L., Higaki, K., Togawa, M., Maegaki, Y., Nanba, E., … Ohno, K. (2012). Chemical chaperone therapy for neuropathic Gaucher disease. In 12th International Child Neurology Congress and the 11th Asian and Oceanian Congress of Child Neurology Brisbane (pp. 50-5)

Layout table for additonal information
Responsible Party: Stephen Pasternak, Neurologist, Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT04405596    
Other Study ID Numbers: REB:115252
First Posted: May 28, 2020    Key Record Dates
Last Update Posted: May 29, 2020
Last Verified: May 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Stephen Pasternak, Lawson Health Research Institute:
Lewy Body Disease
Ambroxol
Cognition
Dementia
Additional relevant MeSH terms:
Layout table for MeSH terms
Dementia
Lewy Body Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Movement Disorders
Neurodegenerative Diseases
Ambroxol
Expectorants
Respiratory System Agents