<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/NCT03812744</url>
  </required_header>
  <id_info>
    <org_study_id>16-391 MR 1610</org_study_id>
    <nct_id>NCT03812744</nct_id>
  </id_info>
  <brief_title>Neurophysiological Effects of Whole Coffee Cherry Extract in Older Adults</brief_title>
  <official_title>Neurophysiological Effects of Whole Coffee Cherry Extract in Older Adults: An fMRI Investigation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Auburn University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Auburn University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study was designed to characterize the changes in the brain and body associated with&#xD;
      whole coffee cherry extract (WCCE). WCCE is a patented extract of whole coffee fruit (coffee&#xD;
      berries) from coffea arabica. Whole coffee cherries are a source of naturally occurring&#xD;
      nutrients. There are no known side effects or allergens associated with WCCE other than that&#xD;
      which would be associated with a consuming typical cup of coffee.&#xD;
&#xD;
      Previous studies suggest that increases in serum concentrations of both serum total and&#xD;
      exosomal brain-derived neurotrophic factors (BDNF) may represent one of the mechanisms&#xD;
      responsible for improved cognitive function after acute WCCE administration. Mild cognitive&#xD;
      impairment (MCI) is an intermediate stage between the expected cognitive decline of normal&#xD;
      aging and the more serious decline of dementia. It can involve problems with memory,&#xD;
      language, thinking and judgment that are greater than normal age-related changes.&#xD;
      Furthermore, MCI is associated with reduced circulating BDNF. Due to earlier studies&#xD;
      reporting the ability of WCCE to stimulate increases in circulating and exosomal BDNF, it has&#xD;
      been postulated that WCCE may also acutely improve cognitive function (as measured using&#xD;
      behavioral tasks and fMRI). The purpose of this study is to extend and elucidate the findings&#xD;
      of previous investigations by examining the acute neurophysiological effects of WCCE using&#xD;
      blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and magnetic&#xD;
      resonance spectroscopy (MRS) employing a double-blind, randomized crossover design to&#xD;
      investigate the acute effects of a single dose of WCCE or placebo (silica oxide) on neuronal&#xD;
      activity in older participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2016</start_date>
  <completion_date type="Actual">November 30, 2018</completion_date>
  <primary_completion_date type="Actual">November 30, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Single-site, randomized, placebo-controlled, cross-over, within-subjects design. Study sessions are no more than 72 hours apart. Visits included pre-post assessments following ingestion of either placebo or WCCE.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Investigators, participants, and the sponsor were all blind.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Behavioral Measures - Change in Go/No-Go Reaction Time</measure>
    <time_frame>Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)</time_frame>
    <description>Response/reaction time for each stimuli will be recorded in ms using E-Prime. Reaction times will be calculated for correct and incorrect trials separately.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Behavioral Measures - Change in N-back Reaction Time</measure>
    <time_frame>Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)</time_frame>
    <description>Response/reaction time for each stimuli will be recorded in ms using E-Prime. Reaction times will be calculated for correct and incorrect trials separately.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Behavioral Measures - Change in Go/No-Go Accuracy</measure>
    <time_frame>Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)</time_frame>
    <description>Accuracy will be determined as the number of trials correct, and errors will be classified as errors of omission or commission.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Behavioral Measures - Change in N-back Accuracy</measure>
    <time_frame>Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)</time_frame>
    <description>Accuracy will be determined as the number of trials correct.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Concentration of Neurometabolites</measure>
    <time_frame>Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)</time_frame>
    <description>Magnetic resonance spectroscopy (MRS) measurements pre/post ingestion. The following are measured: glutamate, glutamine, gamma-aminobutyric acid, N-acetylaspartate, choline, creatine, glutathione, myo-inositol, aspartate, taurine, and lactate. LCModel software performed automatic quantification of in vivo proton MR spectra by analyzing spectra as a linear combination of model spectra from sequence-specific simulations. Water-suppressed spectra were eddy current corrected and quantified using the unsuppressed water signal. Cramer-Rao lower bounds were used as a measure of fit with CRLB &gt; 50% rejected from further analysis. Metabolite concentrations were CSF-corrected, and quantified (in ppm).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Blood Levels of Brain Derived Neurotrophic Factor (BDNF)</measure>
    <time_frame>Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)</time_frame>
    <description>Serum and exosomal BDNF concentrations</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood Oxygen Level Dependent (BOLD) Changes</measure>
    <time_frame>Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)</time_frame>
    <description>Functional magnetic resonance imaging blood-oxygen-level-dependent signal changes across tasks, and during resting state</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Memory Deficits</condition>
  <arm_group>
    <arm_group_label>WCCE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Whole coffee cherry extract (WCCE)</intervention_name>
    <description>100mg WCCE</description>
    <arm_group_label>WCCE</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Capsule [CEBOCAP]</intervention_name>
    <description>Silica Oxide</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Complaints of memory, verified by an informant&#xD;
&#xD;
          -  55 years of age or older&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  MRI contraindications&#xD;
&#xD;
          -  Diagnosis of Alzheimer's Disease or suspected diagnosis at the time of visit by study&#xD;
             personnel&#xD;
&#xD;
          -  Significant cerebrovascular disease&#xD;
&#xD;
          -  History of cardiovascular disease&#xD;
&#xD;
          -  Current or recently prescribed medication known to interfere with peripheral and/or&#xD;
             cerebral blood flow or vascular function&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jennifer L Robinson, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Auburn University</affiliation>
  </overall_official>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>January 19, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>January 19, 2019</last_update_submitted>
  <last_update_submitted_qc>January 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Auburn University</investigator_affiliation>
    <investigator_full_name>Jennifer L. Robinson, Ph.D.</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Memory Disorders</mesh_term>
  </condition_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/NCT03812744
org study id: 16-391 MR 1610
nct id: NCT03812744
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study was designed to characterize the changes in the brain and body associated with
      whole coffee cherry extract (WCCE). WCCE is a patented extract of whole coffee fruit (coffee
      berries) from coffea arabica. Whole coffee cherries are a source of naturally occurring
      nutrients. There are no known side effects or allergens associated with WCCE other than that
      which would be associated with a consuming typical cup of coffee.

      Previous studies suggest that increases in serum concentrations of both serum total and
      exosomal brain-derived neurotrophic factors (BDNF) may represent one of the mechanisms
      responsible for improved cognitive function after acute WCCE administration. Mild cognitive
      impairment (MCI) is an intermediate stage between the expected cognitive decline of normal
      aging and the more serious decline of dementia. It can involve problems with memory,
      language, thinking and judgment that are greater than normal age-related changes.
      Furthermore, MCI is associated with reduced circulating BDNF. Due to earlier studies
      reporting the ability of WCCE to stimulate increases in circulating and exosomal BDNF, it has
      been postulated that WCCE may also acutely improve cognitive function (as measured using
      behavioral tasks and fMRI). The purpose of this study is to extend and elucidate the findings
      of previous investigations by examining the acute neurophysiological effects of WCCE using
      blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and magnetic
      resonance spectroscopy (MRS) employing a double-blind, randomized crossover design to
      investigate the acute effects of a single dose of WCCE or placebo (silica oxide) on neuronal
      activity in older participants.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Single-site, randomized, placebo-controlled, cross-over, within-subjects design. Study sessions are no more than 72 hours apart. Visits included pre-post assessments following ingestion of either placebo or WCCE.
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Investigators, participants, and the sponsor were all blind.
measure: Behavioral Measures - Change in Go/No-Go Reaction Time
time frame: Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)
description: Response/reaction time for each stimuli will be recorded in ms using E-Prime. Reaction times will be calculated for correct and incorrect trials separately.
measure: Behavioral Measures - Change in N-back Reaction Time
time frame: Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)
description: Response/reaction time for each stimuli will be recorded in ms using E-Prime. Reaction times will be calculated for correct and incorrect trials separately.
measure: Behavioral Measures - Change in Go/No-Go Accuracy
time frame: Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)
description: Accuracy will be determined as the number of trials correct, and errors will be classified as errors of omission or commission.
measure: Behavioral Measures - Change in N-back Accuracy
time frame: Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)
description: Accuracy will be determined as the number of trials correct.
measure: Change in Concentration of Neurometabolites
time frame: Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)
description: Magnetic resonance spectroscopy (MRS) measurements pre/post ingestion. The following are measured: glutamate, glutamine, gamma-aminobutyric acid, N-acetylaspartate, choline, creatine, glutathione, myo-inositol, aspartate, taurine, and lactate. LCModel software performed automatic quantification of in vivo proton MR spectra by analyzing spectra as a linear combination of model spectra from sequence-specific simulations. Water-suppressed spectra were eddy current corrected and quantified using the unsuppressed water signal. Cramer-Rao lower bounds were used as a measure of fit with CRLB > 50% rejected from further analysis. Metabolite concentrations were CSF-corrected, and quantified (in ppm).
measure: Change in Blood Levels of Brain Derived Neurotrophic Factor (BDNF)
time frame: Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)
description: Serum and exosomal BDNF concentrations
measure: Blood Oxygen Level Dependent (BOLD) Changes
time frame: Collected pre-drug, post-drug, pre-placebo, and post-placebo; through study completion (4 time points over a 72 hour period)
description: Functional magnetic resonance imaging blood-oxygen-level-dependent signal changes across tasks, and during resting state
arm group label: WCCE
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Whole coffee cherry extract (WCCE)
description: 100mg WCCE
arm group label: WCCE
intervention type: Drug
intervention name: Placebo Oral Capsule [CEBOCAP]
description: Silica Oxide
arm group label: Placebo
criteria: 
gender: All
minimum age: 55 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Jennifer L Robinson, Ph.D.
role: Principal Investigator
affiliation: Auburn University
responsible party type: Principal Investigator
investigator affiliation: Auburn University
investigator full name: Jennifer L. Robinson, Ph.D.
investigator title: Associate Professor
mesh term: Memory Disorders
sharing ipd: Undecided