A Proof of Concept Study of the Prevention of Mild Cognitive Impairment and Eventual Alzheimer's Disease Using F18 Flutemetamol

NCT03274817 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 09-0228
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated study comparing two types of FDA-approved anti-depressants, Escitalopram and Venlafaxine, to placebo, in order to determine if these medications have positive effects on cognition and memory in those who are between the ages of 50 to 89 years old, who are cognitively normal, and who have subjective memory concerns. Research has shown that those who are cognitively normal but report subjective cognitive impairment are more likely to progress to mild cognitive impairment and Alzheimer's disease in the future. Anti-depressants such as Escitalopram and Venlafaxine have been shown to stimulate production of neurons in memory-sensitive areas such as the hippocampus. Therefore, the investigator is researching whether these drugs would help cognition in those with subjective cognitive impairment, and would help to prevent cognitive decline and eventual Alzheimer's disease.

Conditions

Alzheimer Disease

Keywords

Alzheimer's Disease; Depression; Escitalopram; Venlafaxine

Outcome Measures

Primary Outcomes (6)

• Z-score for the hippocampal region of interest in the theta band

  responders show will less increase in score with treatment compared with baseline, in comparison with placebo treated subjects.

  24 Months

• Multivariate Z score for overall theta abnormality in the frontal and parieto-temporal regions;

  Each subject can serve as their own control, z-transformed relative to initial values accessed for each of the endpoints. In addition, each subject can be evaluated relative to age-expected normal values.

  24 Months

• Probability of deterioration from logistic regression predictive of future decline;

  24 Months

• Z-score coherence (synchrony) between right central and parietal regions across all bands;

  Each subject can serve as their own control, z-transformed relative to initial values accessed for each of the endpoints. In addition, each subject can be evaluated relative to age-expected normal values.

  24 Months

• Mean frequency across the total EEG brain spectrum.

  24 Months

• Metabolic reduction in the hippocampal formation (a region including the hippocampal subiculum and the entorhinal cortex) assessed bilaterally.

  24 Months

Secondary Outcomes (3)

• Brief Cognitive Rating Scale Axes I to V total scores

  24 Months

• The Mini-Mental State Examination (MMSE) total scores

  24 Months

• MAC-Q total score

  24 Months

Study Arms (3)

Escitalopram

ACTIVE COMPARATOR

Escitalopram (lexapro) is presently the most widely used selective serotonin reuptake inhibitor (SSRI) antidepressant.

Drug: Escitalopram Pill

Venlafaxine

ACTIVE COMPARATOR

Venlafaxine is a norepinephrine, serotonin and dopamine reuptake inhibitor antidepressant.The specific form of venlafaxine which will be employed is Effexor XR (venlafaxine hydrochloride extended release capsules)

Drug: Venlafaxine Pill

Placebo

PLACEBO COMPARATOR

Subjects randomized to group C will receive placebo tablets, which will be matched to the Lexapro and the Effexor XR as far as possible, and will also be administered on a once daily schedule at baseline.

Drug: Placebo Oral Tablet

Interventions

Escitalopram Pill DRUG

Subjects randomized to group A will receive Lexapro (escitalopram), in an initial, baseline dosage of 5 mg daily.

Also known as: Lexapro

Escitalopram

Venlafaxine Pill DRUG

Subjects randomized to group B will receive Effexor XR (venlafaxine extended release capsules), in an initial baseline dosage of 37.5 mg daily.

Also known as: Effexor XR

Venlafaxine

Placebo Oral Tablet DRUG

Subjects randomized to group C will receive placebo tablets, which will be matched to the Lexapro and the Effexor XR as far as possible, and will also be administered on a once daily schedule at baseline.

Placebo

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have subjective cognitive impairment (SCI) and be free of objective evidence of cognitive impairment. Operationally, this will be defined as subjects with Global Deterioration Scale (GDS) score of stage 2.4
• Subjects must be between 60 and 80 years of age.
• Subjects must have a knowledgeable informant (study partner) who can accompany them to the evaluations, or, when necessary, be available for telephone contact.

You may not qualify if:

• Subjects must be in a position to comply with all of the study procedures described herein.
• Subjects must have a minimum of 12 years of education.
• Subjects must be fluent in English.
• Subjects original language at birth and/or, in childhood, must have been English, alone, or in conjunction with other languages.
• Subjects who have normal brain aging, who are free of subjective cognitive impairment (SCI), and are therefore categorized at GDS stage 1, will be excluded.
• Subjects with MCI or dementia and are therefore categorized as being at GDS stage 3 or greater, will be excluded.
• Subjects with a mini mental status examination (MMSE) score61 of ≤ 27 will be excluded.
• Subjects with a Hamilton Depression Scale (HDS) score ≥ 16,62 signifying the presence of notable depressive symptomatology which warrants treatment, will be excluded.
• Subjects with a primary diagnosis of depression or with a major depression diagnosis will be excluded.
• Subjects with a significant medical, neurologic, or psychiatric condition, including depression or anxiety disorder, that might interfere with cognition will be excluded.
• Subjects with a history of adverse reactions to escitalopram and/or venlaflaxine will be excluded.
• Subjects, who are judged to have had adverse reactions to selective serotonin reuptake inhibitor medications as a class, will be excluded.
• Subjects taking the antibiotic Zyvox (linezolid) or methylene blue therapy or who are planning to have a diagnostic procedure utilizing methylene blue dye, will be excluded.
• Subjects who are on psychoactive or cognitively active medications or who have received such medications in the prior 8 weeks, will be excluded. These excluded medications encompass antidepressant medications, antipsychotic medications, anxiolytic medications, cholinesterase inhibitors, memantine, antiseizure medications, antiparkinsonian medication and other CNS acting medications.
• Subjects with a history of significant cerebrovascular disease will be excluded. This will be identified by one of the following:

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

New York University School of Medicine

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Depression

Interventions

Escitalopram; Venlafaxine Hydrochloride

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Phenethylamines; Ethylamines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids

Study Officials

• Barry Reisberg

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 7, 2017
• Study Start: June 18, 2009
• Primary Completion: September 25, 2019
• Study Completion: September 25, 2019
• Last Updated: June 2, 2020

Record last verified: 2020-05

Locations

US (1)