BDPP Treatment for Mild Cognitive Impairment (MCI) and Prediabetes or Type 2 Diabetes Mellitus (T2DM)

NCT02502253 | Completed Phase 1

• 1 other identifier: IRB00062802
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Mild Cognitive Impairment; Alzheimer's Disease

Outcome Measures

Primary Outcomes (4)

• Assessment of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  4 months

• Confirm brain penetrance of BDPP by measuring levels of BDPP constituents in cerebrospinal fluid (CSF).

  4 months

• Evaluate BDPP effect on mood with Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia.

  4 months

• Evaluate BDPP effect on cognition with measures of memory, executive function, and attention measures (composite)

  4 months

Study Arms (3)

Low dose

EXPERIMENTAL

Drug: grape seed polyphenolic extract, resveratrol

moderate dose

EXPERIMENTAL

Drug: grape seed polyphenolic extract, resveratrol

High dose

EXPERIMENTAL

Drug: grape seed polyphenolic extract, resveratrol

Interventions

grape seed polyphenolic extract, resveratrol DRUG

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.

Also known as: Bioactive Dietary Polyphenol Preparation

High dose; Low dose; moderate dose

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

Resveratrol

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polyphenols; Phenols

Study Officials

• Paul Roserberg, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 20, 2015
• Study Start: June 1, 2015
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: July 22, 2022

Record last verified: 2022-06

Locations

US (1)