<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03274817</url>
  </required_header>
  <id_info>
    <org_study_id>09-0228</org_study_id>
    <nct_id>NCT03274817</nct_id>
  </id_info>
  <brief_title>A Proof of Concept Study of the Prevention of Mild Cognitive Impairment and Eventual Alzheimer's Disease Using F18 Flutemetamol</brief_title>
  <official_title>A Proof of Concept Study of the Prevention of Mild Cognitive Impairment and Eventual Alzheimer's Disease Using F18 Flutemetamol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NYU Langone Health</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an investigator-initiated study comparing two types of FDA-approved anti-depressants,&#xD;
      Escitalopram and Venlafaxine, to placebo, in order to determine if these medications have&#xD;
      positive effects on cognition and memory in those who are between the ages of 50 to 89 years&#xD;
      old, who are cognitively normal, and who have subjective memory concerns. Research has shown&#xD;
      that those who are cognitively normal but report subjective cognitive impairment are more&#xD;
      likely to progress to mild cognitive impairment and Alzheimer's disease in the future.&#xD;
      Anti-depressants such as Escitalopram and Venlafaxine have been shown to stimulate production&#xD;
      of neurons in memory-sensitive areas such as the hippocampus. Therefore, the investigator is&#xD;
      researching whether these drugs would help cognition in those with subjective cognitive&#xD;
      impairment, and would help to prevent cognitive decline and eventual Alzheimer's disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Insufficient Enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">June 18, 2009</start_date>
  <completion_date type="Actual">September 25, 2019</completion_date>
  <primary_completion_date type="Actual">September 25, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Z-score for the hippocampal region of interest in the theta band</measure>
    <time_frame>24 Months</time_frame>
    <description>responders show will less increase in score with treatment compared with baseline, in comparison with placebo treated subjects.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Multivariate Z score for overall theta abnormality in the frontal and parieto-temporal regions;</measure>
    <time_frame>24 Months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Probability of deterioration from logistic regression predictive of future decline;</measure>
    <time_frame>24 Months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Z-score coherence (synchrony) between right central and parietal regions across all bands;</measure>
    <time_frame>24 Months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean frequency across the total EEG brain spectrum.</measure>
    <time_frame>24 Months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Metabolic reduction in the hippocampal formation (a region including the hippocampal subiculum and the entorhinal cortex) assessed bilaterally.</measure>
    <time_frame>24 Months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brief Cognitive Rating Scale Axes I to V total scores</measure>
    <time_frame>24 Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Mini-Mental State Examination (MMSE) total scores</measure>
    <time_frame>24 Months</time_frame>
    <description>30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It is commonly used in medicine and allied health to screen for dementia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MAC-Q total score</measure>
    <time_frame>24 Months</time_frame>
    <description>brief index of memory complaint.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>Escitalopram</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Escitalopram (lexapro) is presently the most widely used selective serotonin reuptake inhibitor (SSRI) antidepressant.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Venlafaxine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Escitalopram Pill</intervention_name>
    <description>Subjects randomized to group A will receive Lexapro (escitalopram), in an initial, baseline dosage of 5 mg daily.</description>
    <arm_group_label>Escitalopram</arm_group_label>
    <other_name>Lexapro</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Venlafaxine Pill</intervention_name>
    <description>Subjects randomized to group B will receive Effexor XR (venlafaxine extended release capsules), in an initial baseline dosage of 37.5 mg daily.</description>
    <arm_group_label>Venlafaxine</arm_group_label>
    <other_name>Effexor XR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>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.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must have subjective cognitive impairment (SCI) and be free of objective&#xD;
             evidence of cognitive impairment. Operationally, this will be defined as subjects with&#xD;
             Global Deterioration Scale (GDS) score of stage 2.4&#xD;
&#xD;
          -  Subjects must be between 60 and 80 years of age.&#xD;
&#xD;
          -  Subjects must have a knowledgeable informant (study partner) who can accompany them to&#xD;
             the evaluations, or, when necessary, be available for telephone contact.&#xD;
&#xD;
          -  Subjects must be otherwise healthy and fulfill all of the inclusion criteria for&#xD;
             participation in the NYU ADC. Exclusion criteria are enumerated below.&#xD;
&#xD;
          -  Subjects must be in a position to comply with all of the study procedures described&#xD;
             herein.&#xD;
&#xD;
          -  Subjects must have a minimum of 12 years of education.&#xD;
&#xD;
          -  Subjects must be fluent in English.&#xD;
&#xD;
          -  Subjects original language at birth and/or, in childhood, must have been English,&#xD;
             alone, or in conjunction with other languages.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who have normal brain aging, who are free of subjective cognitive impairment&#xD;
             (SCI), and are therefore categorized at GDS stage 1, will be excluded.&#xD;
&#xD;
          -  Subjects with MCI or dementia and are therefore categorized as being at GDS stage 3 or&#xD;
             greater, will be excluded.&#xD;
&#xD;
          -  Subjects with a mini mental status examination (MMSE) score61 of ≤ 27 will be&#xD;
             excluded.&#xD;
&#xD;
          -  Subjects with a Hamilton Depression Scale (HDS) score ≥ 16,62 signifying the presence&#xD;
             of notable depressive symptomatology which warrants treatment, will be excluded.&#xD;
&#xD;
          -  Subjects with a primary diagnosis of depression or with a major depression diagnosis&#xD;
             will be excluded.&#xD;
&#xD;
          -  Subjects with a significant medical, neurologic, or psychiatric condition, including&#xD;
             depression or anxiety disorder, that might interfere with cognition will be excluded.&#xD;
&#xD;
          -  Subjects with a history of adverse reactions to escitalopram and/or venlaflaxine will&#xD;
             be excluded.&#xD;
&#xD;
          -  Subjects, who are judged to have had adverse reactions to selective serotonin reuptake&#xD;
             inhibitor medications as a class, will be excluded.&#xD;
&#xD;
          -  Subjects taking the antibiotic Zyvox (linezolid) or methylene blue therapy or who are&#xD;
             planning to have a diagnostic procedure utilizing methylene blue dye, will be&#xD;
             excluded.&#xD;
&#xD;
          -  Subjects who are on psychoactive or cognitively active medications or who have&#xD;
             received such medications in the prior 8 weeks, will be excluded. These excluded&#xD;
             medications encompass antidepressant medications, antipsychotic medications,&#xD;
             anxiolytic medications, cholinesterase inhibitors, memantine, antiseizure medications,&#xD;
             antiparkinsonian medication and other CNS acting medications.&#xD;
&#xD;
          -  Subjects who are receiving other medications or substances with reported neurogenic&#xD;
             enhancer or neurogenic inhibitor effects will not be excluded. The reason for this&#xD;
             inclusionary approach is that just as the effects of neurogenic enhancers on&#xD;
             Alzheimer's disease appears to be complex (specifically, likely useful in prevention,&#xD;
             possibly not useful effects on disease progression), the same complexity apparently&#xD;
             applies to substances with reported neurogenic enhancer or inhibitor effects. For&#xD;
             example, the angiotensin II receptor antagonist losartan has been reported to suppress&#xD;
             running enhanced neurogenesis in the rat.63 This same medication and medication class&#xD;
             has also been reported to be useful in improving memory64 and in the prevention of&#xD;
             Alzheimer's disease, possibly by other mechanisms.65&#xD;
&#xD;
          -  Subjects with a history of significant cerebrovascular disease will be excluded. This&#xD;
             will be identified by one of the following:&#xD;
&#xD;
             i. history of stroke. ii. Any focal signs of significant neuropathology from the&#xD;
             neurological examination.&#xD;
&#xD;
        iii. A score of ≥ 4 on the Rosen modification of the Hachinski Ischemia Scale.66 iv. Focal&#xD;
        pathology on the MRI scan, indicative of history of infarction. l. Past history of brain&#xD;
        damage, seizure, mental retardation or serious neurological disorders.&#xD;
&#xD;
          -  Significant history of alcoholism or drug abuse.&#xD;
&#xD;
          -  Previous history of schizophrenia, mania, or major depression.&#xD;
&#xD;
          -  Severe cardiac, pulmonary, vascular, metabolic, or hematologic conditions.&#xD;
&#xD;
          -  Presence of a cardiac pacemaker.&#xD;
&#xD;
          -  Presence of any metallic device or implant which would contraindicate an MRI (magnetic&#xD;
             resonance imaging) scan of the brain.&#xD;
&#xD;
          -  Physical impairment of such severity as to adversely affect the validity of&#xD;
             psychological testing.&#xD;
&#xD;
          -  Hostility or refusal to cooperate.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Barry Reisberg</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU Langone Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>New York University School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>May 29, 2020</last_update_submitted>
  <last_update_submitted_qc>May 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alzheimer's Disease</keyword>
  <keyword>Depression</keyword>
  <keyword>Escitalopram</keyword>
  <keyword>Venlafaxine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Venlafaxine Hydrochloride</mesh_term>
    <mesh_term>Escitalopram</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03274817
org study id: 09-0228
nct id: NCT03274817
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Care Provider)
measure: Z-score for the hippocampal region of interest in the theta band
time frame: 24 Months
description: responders show will less increase in score with treatment compared with baseline, in comparison with placebo treated subjects.
measure: Multivariate Z score for overall theta abnormality in the frontal and parieto-temporal regions;
time frame: 24 Months
description: 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.
measure: Probability of deterioration from logistic regression predictive of future decline;
time frame: 24 Months
measure: Z-score coherence (synchrony) between right central and parietal regions across all bands;
time frame: 24 Months
description: 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.
measure: Mean frequency across the total EEG brain spectrum.
time frame: 24 Months
measure: Metabolic reduction in the hippocampal formation (a region including the hippocampal subiculum and the entorhinal cortex) assessed bilaterally.
time frame: 24 Months
measure: Brief Cognitive Rating Scale Axes I to V total scores
time frame: 24 Months
measure: The Mini-Mental State Examination (MMSE) total scores
time frame: 24 Months
description: 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It is commonly used in medicine and allied health to screen for dementia.
measure: MAC-Q total score
time frame: 24 Months
description: brief index of memory complaint.
arm group label: Escitalopram
arm group type: Active Comparator
description: Escitalopram (lexapro) is presently the most widely used selective serotonin reuptake inhibitor (SSRI) antidepressant.
arm group label: Venlafaxine
arm group type: Active Comparator
description: 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)
arm group label: Placebo
arm group type: Placebo Comparator
description: 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 type: Drug
intervention name: Escitalopram Pill
description: Subjects randomized to group A will receive Lexapro (escitalopram), in an initial, baseline dosage of 5 mg daily.
arm group label: Escitalopram
other name: Lexapro
intervention type: Drug
intervention name: Venlafaxine Pill
description: Subjects randomized to group B will receive Effexor XR (venlafaxine extended release capsules), in an initial baseline dosage of 37.5 mg daily.
arm group label: Venlafaxine
other name: Effexor XR
intervention type: Drug
intervention name: Placebo Oral Tablet
description: 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.
arm group label: Placebo
criteria: 
gender: All
minimum age: 60 Years
maximum age: 80 Years
healthy volunteers: No
last name: Barry Reisberg
role: Principal Investigator
affiliation: NYU Langone Health
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Cognitive Dysfunction
mesh term: Venlafaxine Hydrochloride
mesh term: Escitalopram
sharing ipd: Undecided