BDPP Treatment for Mild Cognitive Impairment (MCI) and Prediabetes or Type 2 Diabetes Mellitus (T2DM)
Status:
Recruiting
Trial end date:
2022-06-01
Target enrollment:
Participant gender:
Summary
Mild Cognitive Impairment (MCI) represents a group of persons who are at risk of incident
dementia in the near-term. Persons with MCI who have deficits in short-term recall (amnestic
MCI) are at significant risk of incident Alzheimer's disease (AD) (termed prodromal AD), and
thus represent a worthy target for secondary prevention interventions.
There is increasing evidence that risk factors for metabolic syndrome (such as prediabetes
and type 2 diabetes) increase risk of incident cognitive impairment and possibly AD, and
evidence that the neurons of the AD brain are in fact insulin resistant with diminished
glucose uptake under physiological conditions. Thus, persons with MCI and prediabetes or type
2 diabetes may be at particular risk of incident cognitive impairment and AD.
A large clinical trial (ACCORD)1 demonstrated that tight control of peripheral blood glucose
does not improve cognitive (or other health) outcomes in older persons with peripheral
insulin resistance. Thus, there is a need to target cognitive outcomes in persons with MCI
and metabolic risk factors, and a drug targeting insulin resistance with good
blood-brain-barrier (BBB) penetrance can potentially accomplish these objectives. While there
is a phase III study of intranasal insulin targeting this strategy, nutraceuticals offer a
low-tech solution that would be more suitable to future secondary prevention trials in MCI.
Bioactive Dietary Polyphenol Preparation (BDPP) is a combination of two nutraceutical
preparations grape seed polyphenolic extract (GSE), and resveratrol that contain abundant
concentrations of polyphenols. The investigators have found that oral BDPP administration was
associated with improved cognition and brain plasticity long-term potentiation (LTP) in mouse
models of metabolic syndrome and AD, as well as lowering brain amyloid and tau burden in an
AD mouse model2-4. The investigators have demonstrated excellent absorption of oral BDPP in a
small study in humans and similarly excellent CSF penetration of oral BDPP in rats, but it is
crucial to demonstrate safety and CSF penetration of oral BDPP in humans to assess its
potential as a treatment for MCI and prediabetes or type 2 diabetes.