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Ambroxol as a disease-modifying treatment to reduce the risk of cognitive impairment in GBA-associated Parkinson's disease: a multicentre, randomised, double-blind, placebo-controlled, phase II trial. The AMBITIOUS study protocol
Fabiana Colucci, Micol Avenali, Rosita De Micco, Marco Fusar Poli, Silvia Cerri, Mario Stanziano, Ana Bacila, Giada Cuconato et al.. BMJ neurology open, 2023-11-24
Topic: Drug trials: efficacy and safety
BACKGROUND: Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme β-glucocerebrosidase (GCase), are the most frequent genetic risk factor for Parkinson's disease (PD). GBA-related PD (GBA-PD) patients have higher risk of dementia and reduced survival than non-carriers. Preclinical studies and one open-label trial in humans demonstrated that the chaperone ambroxol (ABX) increases GCase levels and modulates α-synuclein levels in the blood and cerebrospinal fluid (CSF). METHODS AND ANALYSIS: In this multicentre, double-blind, placebo-controlled, phase II clinical trial, we randomise patients with GBA-PD in a 1:1 ratio to either oral ABX 1.2 g/day or placebo. The duration of treatment is 52 weeks. Each participant is assessed at baseline and weeks 12, 26, 38, 52 and 78. Changes in the Montreal Cognitive Assessment score and the frequency of mild cognitive impairment and dementia between baseline and weeks 52 are the primary outcome measures. Secondary outcome measures include changes in validated scales/questionnaires assessing motor and non-motor symptoms. Neuroimaging features and CSF neurodegeneration markers are used as surrogate markers of disease progression. GCase activity, ABX and α-synuclein levels are also analysed in blood and CSF. A repeated-measures analysis of variance will be used for elaborating results. The primary analysis will be by intention to treat. ETHICS AND DISSEMINATION: The study and protocols have been approved by the ethics committee of centres. The study is conducted according to good clinical practice and the Declaration of Helsinki. The trial findings will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBERS: NCT05287503, EudraCT 2021-004565-13.
Key findings
- GBA-related PD (GBA-PD) patients have higher risk of dementia and reduced survival than non-carriers.
- Preclinical studies and one open-label trial in humans demonstrated that the chaperone ambroxol (ABX) increases GCase levels and modulates α-synuclein levels in the blood and cerebrospinal fluid (CSF).
- A repeated-measures analysis of variance will be used for elaborating results.
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Study details
- Study designopen-label trial
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and studied in people because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 25 of the 56 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (BMJ neurology open) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | Design recorded as “open-label trial”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38027469) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 25 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 25 of the 56 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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APA 7th
Colucci, F., Avenali, M., De Micco, R., Poli, M. F., Cerri, S., Stanziano, M., et al. (2023). Ambroxol as a disease-modifying treatment to reduce the risk of cognitive impairment in GBA-associated Parkinson's disease: a multicentre, randomised, double-blind, placebo-controlled, phase II trial. The AMBITIOUS study protocol. BMJ neurology open. https://doi.org/10.1136/bmjno-2023-000535
Vancouver
Colucci F, Avenali M, De Micco R, Poli MF, Cerri S, Stanziano M, et al. Ambroxol as a disease-modifying treatment to reduce the risk of cognitive impairment in GBA-associated Parkinson's disease: a multicentre, randomised, double-blind, placebo-controlled, phase II trial. The AMBITIOUS study protocol. BMJ neurology open. 2023. doi:10.1136/bmjno-2023-000535. PMID: 38027469.
BibTeX
@article{colucci2023-38027469,
author = {Colucci, Fabiana and Avenali, Micol and De Micco, Rosita and Poli, Marco Fusar and Cerri, Silvia and Stanziano, Mario and Bacila, Ana and Cuconato, Giada and others},
title = {{Ambroxol as a disease-modifying treatment to reduce the risk of cognitive impairment in GBA-associated Parkinson's disease: a multicentre, randomised, double-blind, placebo-controlled, phase II trial. The AMBITIOUS study protocol}},
journal = {BMJ neurology open},
year = {2023},
doi = {10.1136/bmjno-2023-000535},
pmid = {38027469},
url = {https://doi.org/10.1136/bmjno-2023-000535}
}