This study has been transitioned to CTIS with ID 2024-514012-28-00 check the CTIS register for the current data. Assess the neurological efficacy of ambroxol in adults and children with GD3.
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Lyso-GL1 in CSF
Secondary outcome
• Lyso-GL1, GL-1, chitotriosidase and Lyso-GM3 in plasma
• GL-1 and Lyso-GM3 in CSF
• GCase activity in leukocytes
• Goal Attainment Scaling (GAS)
• Quality of Life (PedsQL)
• Assessment and rating of ataxia (SARA)
• Neuropsychological assessment (ANT/Wechsler scale)
• Behavioural assessment (SDQ/SWAN)
• If epilepsy: seizure control (UMRS, seizure log book)
Background summary
Gaucher disease (GD) is an autosomal recessive lysosomal storage disease (LSD),
caused by bi-allelic mutations in GBA1 resulting in a deficiency of the
lysosomal enzyme glucocerebrosidase (GCase). GD is biochemically characterized
by lysosomal accumulation of glucosylceramide (GL-1) and its deacylated form,
glucosylsphinogosine (Lyso-GL1). Clinically, GD is classified intro three
subtypes (GD1-3). All present with multisystemic disease manifestations (i.e.
enlarged liver and spleen, anaemia). GD2 and GD3 are less common and include
involvement of the central nervous system (CNS). GD3 patients present with
untreatable progressive neurodegenerative disease, i.e. progressive
developmental delay, myoclonic epilepsy, supranuclear gaze palsy and ataxia.
The systemic manifestations of GD can be treated by enzyme replacement therapy
(ERT). However, ERT is not able to cross the blood-brain barrier (BBB) and
hence no treatment for the devastating neurological symptoms is available.
Ambroxol is a small molecule chaperone that has been shown to increase GCase
activity in vitro and is able to cross the BBB. Because classical randomized
controlled trials (RCTs) are unfit to perform due to a low prevalence and
heterogeneity of GD3, we will combine the results of several n-of-1 trials. The
purpose of this study is to evaluate the neurological efficacy of ambroxol in
patients with GD3, using an n-of-1 series.
Study objective
This study has been transitioned to CTIS with ID 2024-514012-28-00 check the CTIS register for the current data.
Assess the neurological efficacy of ambroxol in adults and children with GD3.
Study design
A series of prospective double-blind randomized and placebo-controlled multiple
cross-over, single centre studies within a participant (multiple n-of-1
trials).
Intervention
Each patient receives multiple blocks consisting of three time daily ambroxol
(25 mg/kg/day) alternated with placebo and washout periods.
Study burden and risks
No treatment is available for this severely affected patient group. There is an
unmet medical need to treat this progressive neurodegenerative disease. High
dose ambroxol has been used in several (pre)clinical case studies including
children and adults without any serious adverse events. Because of the
progressive nature of GD3, early innervation is necessary. Therefore paediatric
patients with GD3 are necessary to include. Risks for subject participating in
this trial consist of additional blood draw and lumbar punctures at baseline
and during treatment. As this clinical trial enables a potential treatment for
patients that lack treatment options, we will expect that the benefits
substantially outweigh the burden of participation.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1) The patient or the parent(s) / legal guardian(s) must provide written
informed consent before start of the study;
2) Male and female patients with documented deficiency of GCase activity and
GBA genotype fitting GD3;
3) 3) Male and female patients > 2 years of age;
4) Able to travel to the study site;
5) Patients receive ERT with treatment ongoing at the time of enrollment;
Exclusion criteria
1) The patient is transfusion dependent;
2) The patient has received an investigational product within 30 days prior to
enrollment;
3) Known hypersensitivity reactions, intolerance or adverse reactions to
ambroxol or to the inactive ingredients;
4) Pregnancy, because there are no sufficient data for the use of ambroxol in
pregnant women (see Summary of Product Characteristics (SPC));
5) The patient is lactating. Ambroxol crosses into the breast milk. As there is
no adequate experience in humans to date, ambroxol should not be used in
lactation in a study setting (see SPC);
6) The patient is unwilling or, in the investigator*s opinion, unable to adhere
to the requirements of the study;
7) The patient is unable to swallow powder and has no other enteral access
(e.g. gastrostomy);
8) Any condition or abnormality which may, in the opinion of the investigator,
compromise the safety of patients.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-514012-28-00 |
| EudraCT | EUCTR2021-002550-82-NL |
| CCMO | NL76160.018.21 |