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Efficacy of probucol on cognitive function in Alzheimer's disease: study protocol for a double-blind, placebo-controlled, randomised phase II trial (PIA study)
Virginie Lam, Roger Clarnette, Roslyn Francis, Michael Bynevelt, Gerald Watts, Leon Flicker, Carolyn F Orr, Poh Loh et al.. BMJ open, 2022-02-21
Topic: Drug trials: efficacy and safety
INTRODUCTION: Preclinical, clinical and epidemiological studies support the hypothesis that aberrant systemic metabolism of amyloid beta (Aβ) in the peripheral circulation is causally related to the development of Alzheimer's disease (AD). Specifically, recent studies suggest that increased plasma concentrations of lipoprotein-Aβ compromise the brain microvasculature, resulting in extravasation and retention of the lipoprotein-Aβ moiety. The latter results in an inflammatory response and neurodegeneration ensues. Probucol, a historic cholesterol-lowering drug, has been shown in murine models to suppress lipoprotein-Aβ secretion, concomitant with maintaining blood-brain-barrier function, suppressing neurovascular inflammation and supporting cognitive function. This protocol details the probucol in Alzheimer's study, a drug intervention trial investigating if probucol has potential to attenuate cognitive decline, delay brain atrophy and reduce cerebral amyloid burden in patients with mild-to-moderate AD. METHODS AND ANALYSIS: The study is a phase II, randomised, placebo-controlled, double-blind single-site clinical trial held in Perth, Australia. The target sample is 314 participants with mild-to-moderate AD. Participants will be recruited and randomised (1:1) to a 104-week intervention consisting of placebo induction for 2 weeks followed by 102 weeks of probucol (Lorelco) or placebo. The primary outcome is changed in cognitive performance determined via the Alzheimer's Disease Assessment Scales-Cognitive Subscale test between baseline and 104 weeks. Secondary outcomes measures will be the change in brain structure and function, cerebral amyloid load, quality of life, and the safety and tolerability of Lorelco, after a 104week intervention. ETHICS AND DISSEMINATION: The study has been approved by the Bellberry Limited Human Research Ethics Committee (approval number: HREC2019-11-1063; Version 4, 6 October 2021). Informed consent will be obtained from participants prior to any study procedures being performed. The investigator group will disseminate study findings through peer-reviewed publications, key conferences and local stakeholder events. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000726853).
Key findings
- Specifically, recent studies suggest that increased plasma concentrations of lipoprotein-Aβ compromise the brain microvasculature, resulting in extravasation and retention of the lipoprotein-Aβ moiety.
- The latter results in an inflammatory response and neurodegeneration ensues.
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Study details
- Participants314
- Evidence strengthHigh
How this study scored 61/100
Published in a peer-reviewed journal. Scored zero for study design and effect reported 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 34 of the 56 points we could judge it on, which is 61 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (BMJ open) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 314 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 35190446) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 34 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 34 of the 56 points we could judge it on is 61 out of 100. |
| Total | 61 / 100 | — |
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APA 7th
Lam, V., Clarnette, R., Francis, R., Bynevelt, M., Watts, G., Flicker, L., et al. (2022). Efficacy of probucol on cognitive function in Alzheimer's disease: study protocol for a double-blind, placebo-controlled, randomised phase II trial (PIA study). BMJ open. https://doi.org/10.1136/bmjopen-2021-058826
Vancouver
Lam V, Clarnette R, Francis R, Bynevelt M, Watts G, Flicker L, et al. Efficacy of probucol on cognitive function in Alzheimer's disease: study protocol for a double-blind, placebo-controlled, randomised phase II trial (PIA study). BMJ open. 2022. doi:10.1136/bmjopen-2021-058826. PMID: 35190446.
BibTeX
@article{lam2022-35190446,
author = {Lam, Virginie and Clarnette, Roger and Francis, Roslyn and Bynevelt, Michael and Watts, Gerald and Flicker, Leon and Orr, Carolyn F and Loh, Poh and others},
title = {{Efficacy of probucol on cognitive function in Alzheimer's disease: study protocol for a double-blind, placebo-controlled, randomised phase II trial (PIA study)}},
journal = {BMJ open},
year = {2022},
doi = {10.1136/bmjopen-2021-058826},
pmid = {35190446},
url = {https://doi.org/10.1136/bmjopen-2021-058826}
}