Benfotiamine in Alzheimer's Disease: A Pilot Study

Summary

General Investigational Plan

Study Objectives The goal of this proposal is to determine whether enhancing brain glucose utilization minimizes cognitive decline in patients with Amnestic Mild Cognitive Impairment (AMCI) or mild Alzheimer's disease (AD) dementia. We propose a proof of concept double-blind, placebo controlled pilot study to determine if increasing brain thiamine availability with the investigational new drug benfotiamine, will minimize the decline in glucose utilization and slow the cognitive decline associated with the progression AMCI/AD dementia.

Specifically, our objectives are two-fold:

* To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG).
* To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.

We will also carry out the following secondary objectives:

* Assess if there are differences in secondary clinical outcome measures (NPI, ADCSADL, CDR, Buschke) between benfotiamine and placebo groups and whether specific cognitive domains (ie: activities of daily living, learning and memory verbal memory, behavioral, etc.) are driving these changes.
* Compare ADAS-COG change scores in the benfotiamine and placebo groups within and between strata that were defined by initial cognitive impairment, to attempt to identified the population that most benefits from benfotiamine.
* Compare changes in glucose utilization between the benfotiamine and placebo groups in secondary Regions of Interest (ROIs) including the hippocampus, prefrontal regions and entorhinal cortex.
* Compare changes in whole brain glucose utilization between the benfotiamine and placebo groups using statistical parametric mapping (SPM).
* Assess the correlation between changes in glucose utilization with changes in ADAS Cog.
* Determine if ApoE4 genotype alters the response to benfotiamine.

Conditions

• Alzheimer's Disease

Interventions

DRUG

Benfotiamine

* To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). * To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.

Sponsors & Collaborators

• Burke Rehabilitation Hospital

  collaborator OTHER

• Columbia University

  collaborator OTHER

• National Institute on Aging (NIA)

  collaborator NIH

• Alzheimer's Drug Discovery Foundation

  collaborator OTHER

• Montefiore Medical Center

  collaborator OTHER

• Burke Medical Research Institute

  lead OTHER

Principal Investigators

• Gary E Gibson, Ph.D. · Burke Medical Research Institute

• Pasquale Fonzetti, MD, PhD · Burke Rehabilitation Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-02-15

Primary Completion

2020-07-20

Completion

2020-09-08

Countries

• United States

Study Locations