Dosage and Efficacy of Probucol-induced apoE to Negate Cognitive Deterioration (DEPEND)
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|ClinicalTrials.gov Identifier: NCT02707458|
Recruitment Status : Completed
First Posted : March 14, 2016
Last Update Posted : January 31, 2018
|Condition or disease||Intervention/treatment||Phase|
|Dementia of the Alzheimer Type Age-related Cognitive Decline Mild Cognitive Impairment Due to Alzheimer Disease||Drug: Probucol||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Dose-finding and Proof-of-concept Trial of Probucol to Increase Availability of CSF Apolipoprotein-E|
|Study Start Date :||April 2016|
|Actual Primary Completion Date :||March 2017|
|Actual Study Completion Date :||March 2017|
Experimental: Single arm
All subjects will receive probucol, starting with a fixed dose of 600 mg daily following the evening meal. The variable plasma concentrations achieved and the resulting modification in concentration of CSF apoE will suggest an ideal range of plasma concentrations for use of the drug as an inducer of increased availability of apoE in the CSF. The known dose-proportionality of the drug in plasma will then be used to estimate an ideal individualized dose for each participant. The effects of such individualized dosage will be tested over 1 year of follow-up observations, searching for treatment effects on CSF apoE and for evidence of other treatment effects, particularly including adverse effects.
Probucol was used with good effect for more than a decade in Canada and the US to reduce plasma cholesterol. Although withdrawn from the Canadian and US markets by its manufacturer for commercial reasons, it is still widely used for this purpose in Japan and Korea. Over the past decade, long-term follow-up studies in Asian populations at high risk of cardiovascular events have shown that the drug reduces the incidence of these events in a manner not unlike "statin" drugs used widely in Canada and the US.
Other Name: Lorelco (trade name in Japan)
- Plasma concentration of probucol following test dose [ Time Frame: three months ]Participants are given a test dose of probucol 600 mg q.d. Plasma concentration of probucol and cerebrospinal fluid (CSF) concentrations of probucol and apolipoprotein E (apoE) are measured at baseline and after 3 months. Results should suggest a range of plasma concentrations associated with an increase in CSF apoE by at least 50%. Relying on dose-proportionality of plasma concentration achieved, an estimated optimum individual dose for target levels of apolipoprotein E induction is then calculated.
- Apolipoprotein concentration in CSF before and after treatment with probucol at individualized dose [ Time Frame: One year on individualized dosing, as suggested by experimental observations above ]After a washout period => 2 months, participants will initiate treatment with probucol at individualized dosage determined in Outcome 1. Results after 1 year will establish whether such individualized dosage of probucol achieves 'target engagement' of specified increase in CSF apoE, to be tested subsequently for its ability to prevent progression of pre-symptomatic Alzheimer disease.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02707458
|Douglas Hospital Research Centre|
|Montreal, Quebec, Canada, H4H1R3|
|Principal Investigator:||John C Breitner, MD, MPH||Douglas Hospital Research Centre & McGill University Faculty of Medicine|