Whole Coffee Cherry Study

Study Overview
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Brief Summary
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There has been increasing interest in natural dietary supplements that may support healthy cognition. Recent studies have demonstrated promising effects of bioactive phytochemicals (e.g., polyphenols) on cardiovascular and endocrine health outcomes. As such, an increasingly intriguing line of inquiry is whether materials high in these compounds may also have effects on psychological measures. Preliminary evidence suggests that polyphenols may improve cognition, for example, particularly in aging populations. Whole coffee cherry extract (WCCE; otherwise known as the generally-recognized-as-safe (GRAS) supplement Neurofactor(TM)), is a proprietary, safe, powdered extract of whole coffee cherries from coffea arabica with high levels of polyphenols and substantially low (<2%; <4mg) levels of caffeine. WCCE has been previously associated with increased serum concentrations of both circulating and exosomal brain derived neurotrophic factor (BDNF), in addition to increased alertness and decreased fatigue. However, few well-powered and well-designed studies have been conducted despite the mounting preliminary evidence. Here, the investigators propose a study to examine the long-term effects of a 200mg dose of WCCE on measures of cognition.

Detailed Description
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The investigators will conduct a virtual study whereby participants will be given either 200mg WCCE or placebo to take every day for 28 days. Every 7 days, participants will take a cognitive assessment via the internet using a platform called Millisecond (https://www.millisecond.com/). The cognitive assessment will be composed of tasks that broadly test working memory, focus, and attention. Compliance checks will be administered daily via the participant's smartphone. This study will be conducted in a double-blind fashion, such that the experimental team and the participants are unaware of group assignment (200mg vs. placebo). Blinding information will be held by the study sponsor, VDF FutureCeuticals, Inc. Group assignment will be determined by random number generator, with restrictions to ensure equal group sizes, and equal distribution of males/females in each group. Participants, between 40-65 years of age, with no known psychiatric or neurological conditions, will be recruited from the general community via online advertisements, social media posts, community flyers, and newspaper ads (if needed). Participants will be excluded if they are taking medications known to alter cognitive functioning (psychotropic medications such as fluoxetine, benzodiazepines, etc. or other medications such as insulin). The primary variables of interest will be the behavioral performance on the cognitive tasks over time, inclusive of reaction time and accuracy. Compensation will be commensurate with study participation, with a maximum payout of $125.

Official Title
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Longitudinal Study to Assess the Effects of Whole Coffee Cherry Extract (WCCE)

Conditions
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Effect of Drug

Intervention / Treatment
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* Dietary Supplement: Whole coffee cherry extract
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 40-65 years of age No diagnosed psychiatric or neurological condition Reliable internet service Moderate computer literacy Individuals must have a smartphone Individuals must have a laptop, desktop, or iPad Exclusion Criteria: Individuals taking medications known to alter cognitive functioning (e.g., psychotropic medications such as fluoxetine, benzodiazepines, etc.) Individuals taking medications that alter metabolic function, such as insulin or metformin. Shift workers Health conditions that would prevent an individual from successfully completing the study (I.e., motor control conditions such as Parkinson's, or psychiatric conditions such as ADHD) Individuals with metabolic conditions Have had or currently have cancer Have taken CBD or multivitamins in the last 2 weeks Individuals with unreliable or no internet access/service Individuals who are unable to use a smartphone or are lacking the computer literacy necessary to complete the study remotely Individuals without a laptop, desktop or iPad that would prevent them from completing the study.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly assigned to one of two groups - study materials (whole coffee cherry extract (WCCE) or placebo).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>The placebo will be a simple microcellulose, which is generally-recognized-as-safe (GRAS) and commonly used in food products. | Dietary Supplement: Placebo<br>* Placebo for comparison to WCCE<br>|
| Active Comparator: Whole coffee cherry extract<br>Whole coffee cherry extract (WCCE; otherwise known as the generally-recognized-as-safe (GRAS) supplement Neurofactor(TM)), is a proprietary, safe, powdered extract of whole coffee cherries from coffea arabica with high levels of polyphenols and substantially low (<2%; <4mg) levels of caffeine. The only content of the supplement is WCCE - there are no excipients, binders, or flow agents, nor are there any other materials. The coffee cherry is subjected to a food-grade water ethanol extraction; thus, after extraction, only 100% coffee-based components remain. 200mg of WCCE will be administered daily for 28 days. | Dietary Supplement: Whole coffee cherry extract<br>* 200mg WCCE<br>* Other names: CCE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioral Measures - Change in Go/NoGo Reaction Time | Response/reaction time/accuracy for each stimuli will be recorded in ms using Inquisit. Reaction times will be calculated for correct and incorrect trials separately. | Collected at baseline (pre- and post-consumption) and then once weekly (pre-consumption) through the duration of the study (approximately 28 days) | 
| Behavioral Measures - Change in N-back Reaction Time | Response/reaction/accuracy time for each stimuli will be recorded in ms using Inquisit. Reaction times will be calculated for correct and incorrect trials separately. | Collected at baseline (pre- and post-consumption) and then once weekly (pre-consumption) through the duration of the study (approximately 28 days) | 
| Behavioral Measures - Change in Face-Name Reaction Time | Response/reaction time/accuracy for each stimuli will be recorded in ms using Inquisit. Reaction times will be calculated for correct and incorrect trials separately. | Collected at baseline (pre- and post-consumption) and then once weekly (pre-consumption) through the duration of the study (approximately 28 days) | 
| Behavioral Measures - Change in Stroop Reaction Time | Response/reaction time/accuracy for each stimuli will be recorded in ms using Inquisit. Reaction times will be calculated for correct and incorrect trials separately. | Collected at baseline (pre- and post-consumption) and then once weekly (pre-consumption) through the duration of the study (approximately 28 days) | 
| Behavioral Measures - Change in Flanker Task Reaction Time | Response/reaction time/accuracy for each stimuli will be recorded in ms using Inquisit. Reaction times will be calculated for correct and incorrect trials separately. | Collected at baseline (pre- and post-consumption) and then once weekly (pre-consumption) through the duration of the study (approximately 28 days) | 
| Behavioral Measures - Change in Symbol Search Reaction Time | Response/reaction time/accuracy for each stimuli will be recorded in ms using Inquisit. Reaction times will be calculated for correct and incorrect trials separately. | Collected at baseline (pre- and post-consumption) and then once weekly (pre-consumption) through the duration of the study (approximately 28 days) | 
| Behavioral Measures - Change in Trail Making Reaction Time | Response/reaction time/accuracy for each stimuli will be recorded in ms using Inquisit. Reaction times will be calculated for correct and incorrect trials separately. | Collected at baseline (pre- and post-consumption) and then once weekly (pre-consumption) through the duration of the study (approximately 28 days) | 
| Behavioral Measures - Change in Face in the Crowd Time | Response/reaction time/accuracy for each stimuli will be recorded in ms using Inquisit. Reaction times will be calculated for correct and incorrect trials separately. | Collected at baseline (pre- and post-consumption) and then once weekly (pre-consumption) through the duration of the study (approximately 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Self-reported Sleep | The investigators will assess changes in the amount of sleep a participant had on a daily basis for the entire duration of the study via a single daily question asking about the number of hours of sleep the participant had the night before. | The question will be administered daily for the duration of the study (approximately 28 days) | 
| Weekly Self-reported Sleep Hygiene | The investigators will assess changes in sleep via an in-house questionnaire (administered every 7 days for the entire length of the study) that inquires about the quality of sleep for the past 7 days, as well as how the participant would rate their sleep for the night prior to the assessment. These questions are scored as 1 = excellent, 2 = good, 3 = average, 4 = poor, and 5 = terrible. | Questions are administered weekly for the duration of the study (approximately 28 days) | 
| Weekly Self-reported Mood | The investigators will assess changes in mood every 7 days for the duration of the study. This questionnaire, developed in-house, asks about how often the participant has felt alert, focused, attentive, in-control, sleepy, determined, motivated, happy, and upset the participant has felt in the last 7 days. The scale is scored as 1 = always, 2 = most of the time, 3 = about half of the time, 4 = sometimes, and 5 = never. | The questionnaire is administered weekly for the duration of the study (approximately 28 days) | 
| Daily Self-reported Mood | The investigators will assess changes in mood via a daily question about how good/bad the participant feels on a scale of 0-100 (0 being worst they have ever felt, and 100 being the best they have ever felt). | The question will be administered daily for the duration of the study (approximately 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coffee cherry, cognition, virtual study, internet