Clinical trial NCT02502253: BDPP Treatment for Mild Cognitive Impairment (MCI) and Prediabetes or Type 2 Diabetes Mellitus (T2DM)
Official title: BDPP Treatment for Mild Cognitive Impairment (MCI) and Prediabetes or Type 2 Diabetes Mellitus (T2DM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Mild Cognitive Impairment
Alzheimer's Disease
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Icahn School of Medicine at Mount Sinai
First posted: 2015-07-20
Enrollment: 14
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: Inclusion Criteria:

* Age 50-90 years inclusive
* Amnestic MCI
* Impaired fasting glucose (IFG), defined by American Diabetes Association criteria (fasting blood sugar between 100 and 125 mg/dl) or clinically stable type 2 diabetes
* Knowledgeable informant (KI) who spends at least 5 hours/week with the participant and can provide information about the participant's psychosocial functioning

Exclusion Criteria:

* Deemed too unstable medically or neurologically to safely enroll in trial of research medication
* Type 1 Diabetes Mellitus
* Diagnosis of dementia due to Alzheimer's disease

Primary outcomes:
measure: Assessment of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 4 months
measure: Confirm brain penetrance of BDPP by measuring levels of BDPP constituents in cerebrospinal fluid (CSF).
timeFrame: 4 months
measure: Evaluate BDPP effect on mood with Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia.
timeFrame: 4 months
measure: Evaluate BDPP effect on cognition with measures of memory, executive function, and attention measures (composite)
timeFrame: 4 months
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Paul Roserberg, MD
role: PRINCIPAL_INVESTIGATOR
References: