Dosage and Efficacy of Probucol-induced apoE to Negate Cognitive Deterioration — DEPEND  

Age-related Cognitive Decline Clinical Trial

Official title: Dose-finding and Proof-of-concept Trial of Probucol to Increase Availability of CSF Apolipoprotein-E

Status Completed

Clinical Trial Summary

DEPEND is an open-label but dosage-masked trial of the retired cholesterol-lowering drug probucol as an agent to increase availability of apolipoprotein E (apoE) in the cerebrospinal fluid (CSF) of cognitively intact older persons at risk of Alzheimer's dementia. Absorption of oral probucol is variable. In a sample of 23 cognitively intact persons over age 55, DEPEND will therefore develop an algorithm to prescribe individualized dosing to achieve plasma concentration that will likely increase availability of CSF apoE. These persons will then use their individualized dosage for 12 months to assess longer-term effects of the drug on CSF apoE concentration, while monitoring closely for evidence of adverse consequences of use.

Clinical Trial Description

Probucol is a cholesterol-lowering drug that has been removed from the market in Canada and the US, but remains in clinical use in Asia. In rodents, probucol increases synthesis and availability of apolipoprotein E (apoE) in the cerebrospinal fluid (CSF). ApoE is the protein product of the polymorphic gene APOE, allelic variation in which remains the strongest known risk factor (other than age itself) for Alzheimer's dementia. Oral Probucol is absorbed variably. Administration of a single, fixed dose therefore results in a wide range of plasma concentrations when the drug is given to various individuals in a fixed dosage. Limited human data suggest that higher plasma and CSF concentrations of probucol result in stronger increases in CSF apoE concentration. The dual aims of DEPEND are therefore 1) to develop an individualized dosing regimen that will result in plasma concentrations that are likely to increase CSF apoE concentration by 50%; and 2) to treat 20 persons at elevated risk of Alzheimer's dementia, each at his/her ideal individual dosage, for 12 months, observing the resulting change in CSF concentrations of apoE. Simultaneously, subjects will be observed carefully for evidence of any treatment effects on cognition or other probable markers of progression in pre-clinical Alzheimer's disease, as well as safety risks that might deter further human experimentation with the drug. ;

Related Conditions & MeSH terms

• Age-related Cognitive Decline
• Alzheimer Disease
• Cognitive Dysfunction
• Dementia
• Dementia of the Alzheimer Type
• Mild Cognitive Impairment Due to Alzheimer Disease

• NCT number: NCT02707458
• Study type: Interventional
• Source: Douglas Mental Health University Institute
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2016
• Completion date: March 2017