World Data on Ambroxol for Patients With GD and GBA Related PD

IIR REGISTRY for the Collection of Real World Data on the Safety and Efficacy of Ambroxol for Patients With Gaucher Disease or GBA Carriers With Parkinson Disease

Ambroxol hydrochloride is an oral mucolytic drug available over-the-counter for many years as cough medicine. In 2009 it was found to also act as a pharmacological chaperone (PC) for mutant glucocerebrosidase, albeit in a several-fold higher dose. Unfortunately, due to its low cost, there have been no pharma-driven clinical trials to establish the use of ambroxol. Thus, data are needed on the safety and efficacy of ambroxol for patients with Gaucher disease (GD).

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Gaucher Disease; GBA Gene Mutation

Detailed Description

The three decades of success of enzyme replacement therapy (ERT) for patients with type 1 Gaucher disease (GD1) have been just a partial success to those patients with the more severe neuronopathic forms, particularly the children with myoclonic epilepsy or the infants with type 2 GD.

Ambroxol hydrochloride is an oral mucolytic drug, available over-the-counter (OTC) for many years as cough medicine. In 2009 it was found (in-vitro) to also act as a pharmacological chaperone (PC) for mutant glucocerebrosidase (GCase), albeit in a several-fold higher dose . Unfortunately, due to its low cost, there have been no pharma-driven clinical trials to establish the use of ambroxol.

In an attempt to provide the proof of concept to the potential use of Ambroxol as PC for patients with GD, the Gaucher Clinic at Shaare Zedek Medical Center in Jerusalem, Israel, has treated 12 adult patients with GD1, all untreated with any specific treatment for GD [whether ERT or substrate reduction therapy (SRT),] with Ambroxol at the OTC dose of 150mg/day for a period of 6 months; this was not a formal clinical trial, but rather an audit of a series of patients receiving this drug via the employment of the Israeli Ministry of Health Form 29c to prescribe it for an off-label indication. A single patient, the thinnest of the group with a BMI of 17.1, achieved a robust response relative to baseline similar to ERT.

In 2016, a group from Japan has demonstrated impressive neurological response using high-dose Ambroxol (a marked decrease in seizure frequency, improvement of myoclonus, ability to walk for a bedridden patient, improvement in the latency of I-V waves and threshold of ABR) with dramatic change in daily activities and quality of life (QOL). These encouraging results, that were confirmed in a larger series, yet unpublished, have further led to the conduction of an investigator-initiated-research (IIR) clinical trial in London by Prof A Schapira, which has recently been published (January 13, 2020 JAMA Neurology), wherein newly diagnosed Parkinson patients received high dose Ambroxol, with good safety results

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Recruiting
    • Shaare Zedek Medical Center
  • Please Select...
    • Jerusalem, Please Select..., Israel, 9103102
      • Recruiting
      • Shaare Zedek Medical Center
      • Contact: Joleen Istaiti, MBA; Phone Number: +97226555143; Email: joleenist@szmc.org.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 100 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Gaucher disease type 1,2,3 (a,b,c) and patients with GBA-related Parkinson disease.

Description

Inclusion Criteria:

• patients with Gaucher disease type 1,2 or 3(a,b,c).
• patients with GBA-related Parkinson disease.

Exclusion Criteria:

• None.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Gaucher disease patients; Patients with type 1,2,3 Gaucher disease.
GBA carriers with Parkinson disease; Patients with Parkinson disease GBA related (carriers)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establishing a registry to be used as a reference for patients,parents and physicians, who consider using Ambroxol	With no specific treatment to offer for patients (particularly children and young adults) with nGD, and with all the above-mentioned encouraging preliminary reports, in our current era of rapidly spreading information (in many meetings worldwide, in the internet and via the social media) individual patients in many countries have started to receive off-label Ambroxol by their treating physicians and a few case reports have been published from Korea , Israel and Canada . In order to upscale the level of evidence from anecdotal reports to an observational study, we herein suggest to establish a specific IIR, wherein the "R" stands for a "Registry", that may be used as a reference for patients , parents and physicians, who consider using Ambroxol.	10 years
Safety Outcome	By reporting adverse events	10 years

Collaborators and Investigators

• Sponsor: Shaare Zedek Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 6, 2020
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): January 31, 2024

Study Registration Dates

• First Submitted: May 10, 2020
• First Submitted That Met QC Criteria: May 13, 2020
• First Posted (ACTUAL): May 15, 2020

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 12, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Gaucher Disease; Ambroxol; GBA carriers with Parkinson disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Parkinson Disease; Gaucher Disease
• Other Study ID Numbers: 0097-20-SZMC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No