Clinical trial

Ambroxol as a Novel Disease Modifying Treatment for Lewy Body Dementia

ID

Name

REB:115252

Description

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.

Trial arms

Trial start

2025-01-01

Estimated PCD

2026-01-01

Trial end

2027-01-01

Status

Not yet recruiting

Phase

Early phase I

Treatment

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).

Arms:

Ambroxol

Other names:

Mucosolvan

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).

Arms:

Placebo

Size

15

Primary endpoint

Change in Mini Mental State Examination score from baseline over time

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

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

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

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

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

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

Change in blood analyses from baseline over time

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

Change in urine analyses from baseline over time

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

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

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

Baseline, week 10, week 52

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

Baseline, week 10, week 52

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

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

Eligibility 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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 15, 'type': 'ESTIMATED'}}

Updated at

2023-12-13

1 organization

1 product

1 indication

Organization

Lawson Health Research Institute

Product

Indication

Lewy Body Disease