Ambroxol as a Novel Disease Modifying Treatment for Lewy Body Dementia

NCT04405596 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: REB:115252
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Lewy Body Disease

Keywords

Lewy Body Disease; Ambroxol; Cognition; Dementia

Outcome Measures

Primary Outcomes (12)

• Change in Mini Mental State Examination score from baseline over time

  Monitor safety using frequent cognitive evaluations using the mini mental state examination. Lower scores are indicative of worsening cognitive impairment \[score range: 0-30\]

  Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52

• Change in the incidence, nature and severity of AE's and SAE's from baseline

  Change in the number of participants with AE's and SAE's

  Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52

• Change in the number of participants with treatment discontinuations and study discontinuation due to AEs from baseline

  Change from baseline in the number of participants with treatment and/or study discontinuation will be used to demonstrate safety and tolerability

  Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52

• Change in the number of participants with electrocardiogram (ECG) abnormalities

  Change from baseline in the number of participants with clinically significant ECG abnormalities (QT interval) to demonstrate safety

  Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52

• Change from baseline the number of participants with abnormal changes in hemodynamic values while seated

  Changes in hemodynamic values from baseline over time to demonstrate safety

  Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52

• Change from baseline the number of participants with abnormal changes in hemodynamic values while standing

  Changes in hemodynamic values from baseline over time to demonstrate safety

  Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52

• Change in blood analyses from baseline over time

  Change from baseline in number of participants with abnormal changes in clinical laboratory blood tests from baseline over time for safety

  Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52

• Change in urine analyses from baseline over time

  Change from baseline in number of participants with abnormal changes in clinical laboratory urine tests from baseline over time for safety

  Baseline, week 4, week 10, week 18, week 26, week 34, week 42, week 52

• Change from baseline in plasma concentrations of Ambroxol from blood sample

  Change in plasma Ambroxol concentrations from blood sample from baseline

  Baseline, week 4, week 10, week 26, week 52

• Change from baseline in cerebrospinal fluid (CSF) concentrations of Ambroxol at specified time points

  Change in Ambroxol concentrations from cerebrospinal fluid sample from baseline

  Baseline, week 10, week 52

• Change from baseline in enzyme β-Glucocerebrosidase (GCase) concentration levels in CSF

  Change in GCase concentration in the CSF from baseline

  Baseline, week 10, week 52

• Change from baseline in enzyme β-Glucocerebrosidase (GCase) concentration levels in white blood cells

  Change in white blood cell GCase concentrations from baseline

  Baseline, week 4, week 10, week 26, week 52

Secondary Outcomes (13)

• Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

  Baseline, week 26, and week 52

• Clinician's Global Impression of Change (CGIC)

  Baseline, week 26, and week 52

• Montreal Cognitive Assessment (MoCA)

  Baseline, week 26, and week 52

• Trail making test A and B to assess cognitive function

  Baseline, week 26, and week 52

• Parkinson's disease - Cognitive rating scale to assess cognitive function

  Baseline, week 26, and week 52

Study Arms (2)

Ambroxol

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Participants receive capsules visually identical to the experimental groups but without active ingredients.

Other: Placebo

Interventions

Ambroxol Hydrochloride DRUG

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).

Also known as: Mucosolvan

Ambroxol

Placebo OTHER

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).

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Probable diagnosis of Lewy Body Dementia
• Age greater than 50 years old
• Montreal Cognitive Assessment (MoCA) score: 24-18
• Patients must have a responsible caregiver = 4days/week
• 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

You may not qualify if:

• Evidence of stroke or other neurological condition
• 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.)
• Contraindication to MRI e.g. presence of metal fragments in head or eye, implanted electrical devices or conductive implants or devices (pacemakers, neurostimulators).
• Unable to undergo DAT-scan
• Depression that is, in the opinion of the investigator, significant enough to interfere with neuropsychology and safety assessments
• Females who are pregnant or breastfeeding, or planning to conceive within the study period
• 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.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

Parkwood Institute

London, Ontario, N6C0A7, Canada

Location

Related Publications (22)

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  BACKGROUND

MeSH Terms

Conditions

Lewy Body Disease; Dementia

Interventions

Ambroxol

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Bromhexine; Aniline Compounds; Amines; Organic Chemicals; Cyclohexylamines

Central Study Contacts

Stephen Pasternak, MD, PhD

CONTACT

519-646-6000; spasternak@robarts.ca

Carolina Silveira, PhD

CONTACT

519-646-6100; Carolina.Silveira@sjhc.london.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurologist

Study Record Dates

• First Submitted: April 29, 2020
• First Posted: May 28, 2020
• Study Start: January 1, 2025
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 13, 2023

Record last verified: 2023-12

Locations

CA (1)