A Proof of Concept Study of the Prevention of Mild Cognitive Impairment and Eventual Alzheimer's Disease Using F18 Flutemetamol
Overview
- Phase
- Phase 1
- Intervention
- Escitalopram Pill
- Conditions
- Alzheimer Disease
- Sponsor
- NYU Langone Health
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Probability of deterioration from logistic regression predictive of future decline;
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Subjects must be otherwise healthy and fulfill all of the inclusion criteria for participation in the NYU ADC. Exclusion criteria are enumerated below.
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Escitalopram
Escitalopram (lexapro) is presently the most widely used selective serotonin reuptake inhibitor (SSRI) antidepressant.
Intervention: Escitalopram Pill
Venlafaxine
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)
Intervention: Venlafaxine Pill
Placebo
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.
Intervention: Placebo Oral Tablet
Outcomes
Primary Outcomes
Probability of deterioration from logistic regression predictive of future decline;
Time Frame: 24 Months
Z-score coherence (synchrony) between right central and parietal regions across all bands;
Time Frame: 24 Months
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.
Z-score for the hippocampal region of interest in the theta band
Time Frame: 24 Months
responders show will less increase in score with treatment compared with baseline, in comparison with placebo treated subjects.
Multivariate Z score for overall theta abnormality in the frontal and parieto-temporal regions;
Time Frame: 24 Months
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.
Mean frequency across the total EEG brain spectrum.
Time Frame: 24 Months
Metabolic reduction in the hippocampal formation (a region including the hippocampal subiculum and the entorhinal cortex) assessed bilaterally.
Time Frame: 24 Months
Secondary Outcomes
- Brief Cognitive Rating Scale Axes I to V total scores(24 Months)
- MAC-Q total score(24 Months)
- The Mini-Mental State Examination (MMSE) total scores(24 Months)