Clinical trial NCT05008549: A Study to Assess the Synergistic Effects of a Cranberry Beverage on Cognitive Function
Official title: A Randomized, Double-blinded, Placebo-controlled, Crossover Study, to Assess the Synergistic Effects of a Cranberry Beverage on Cognitive Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Attention
Mood
Lead sponsor: Ocean Spray Cranberries, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Atlantia Food Clinical Trials
First posted: 2021-08-17
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A randomized, double-blinded, placebo-controlled, crossover study, to assess the synergistic effects of a cranberry beverage on cognitive function in healthy adults aged 18-45.
Primary purpose: OTHER

Brief summary: This study aims to determine the effect short-term dosing (7 days) of a placebo beverage, cranberry juice, cranberry juice + lemon balm extract, cranberry juice + tart cherry powder, or cranberry juice + L-theanine or L-theanine beverage on cognitive function and mood in healthy adults (18-45 years). The study will include measures of attention, alertness, performance, and mood/stress.

Detailed description: 1.1 Background information Berries from the Vaccinium genus have been reported to improve some measures of cognitive function in healthy adults. There is evidence that the polyphenols contained in berries and other plant foods may play a role in this regard. Among the plant sources of polyphenols, lemon balm and tart cherry reported to have positive effects on cognitive function in randomized controlled trials (RCTs).

L-theanine is an amino acid present almost exclusively in the tea plant (Camellia sinesis). L-theanine crosses the blood-brain barrier and has been shown to increase serotonin and dopamine production in rats. A recent systematic review of RCTs that evaluated the effect of supplemental L-theanine on stress concluded that L-theanine may assist in the reduction of stress.

Given that plant bioactives may have varying mechanisms to support cognitive health, the aim of this study is as follows:

Aim 1: To determine the effect short-term dosing (7 days) of a placebo beverage, cranberry juice, cranberry juice + lemon balm extract, cranberry juice + tart cherry powder, or cranberry juice + L-theanine or L-theanine beverage on cognitive function and mood in healthy adults (18-45 years). The study will include measures of attention, alertness, performance, and mood/stress.

1.2 Investigational product

Beverage to be tested:

* 100% cranberry juice (8 oz, Ocean Spray)
* 100% cranberry juice (8 oz) + lemon balm extract (300 mg)
* 100% cranberry juice (8 oz) + tart cherry powder (3 g)
* 100% cranberry juice (8 oz) + L-theanine (200 mg)
* L-theanine (200 mg) + placebo (matched for color, taste, calories)
* placebo (matched for color, taste, calories) 1.3 Rationale for conducting the clinical trial There is scientific support for Vaccinium berries to be of benefit to cognitive health. However, this has not be specifically tested in cranberries (Vaccinium macrocarpon). Furthermore, the individual effects of the other ingredients to be tested in this trial have been found to have positive effects on cognitive health but whether there are added effects with cranberry is not known.

  2 OBJECTIVES 2.1 Primary objective To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on attention.

2.2 Primary endpoint variable

* Change in Accuracy of Attention composite scores outcomes from Baseline to each treatment phase (V3-8), assessed using the COMPASS cognitive assessment tool.
* Change in Speed of Attention composite scores outcomes from Baseline to each treatment phase (V3-8), assessed using the COMPASS cognitive assessment tool.

2.3 Secondary objectives To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on measures of focus, alertness, and cognition.

To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on mood and stress.

2.4 Secondary endpoint variables

* Focus: Change in Overall % accuracy scores outcomes from Baseline to each treatment phase (V3-8), assessed using the STROOP task in the COMPASS cognitive assessment tool.
* Alertness: Change in Alertness scores outcomes from Baseline to each treatment phase (V3-8), assessed using the self-rated Alertness VAS scale in the COMPASS cognitive assessment tool.
* Cognitive Performance:

  * Change in Accuracy of Performance composite scores outcomes from Baseline to each treatment phase (V3-8), assessed using the COMPASS cognitive assessment tool.
  * Change in Speed of Performance composite scores outcomes from Baseline to each treatment phase (V3-8), assessed using the COMPASS cognitive assessment tool.
* Mood: Change in Total Mood Disturbance scores from Baseline to each subsequent visit (V3-8), assessed using the Profile of Mood States-Short Questionnaire.
* Stress: Change in salivary cortisol from Baseline to each treatment phase (V3-8).

2.5 Exploratory objectives Dependent upon the outcome of the Primary and Secondary objectives, additional outcomes from the COMPASS cognitive assessment tool may be analyzed further to assess the impact of the investigational product on various domains of cognition.

Eligibility criteria: Inclusion Criteria:

To be eligible for inclusion, the participant must fulfil all of the following criteria:

1. Be able to give written informed consent and willing/able to comply with study procedures.
2. Be between 18 and 45 years, inclusive.
3. Is in general good health, as determined by the investigator.
4. Has a BMI between ≥20 - ≤35 kg/m2.
5. Has had a stable body weight (≤5 % change) over the past 3-months.
6. Has a Beck Depression Inventory II score ≤20 at screening.
7. Willing to discontinue consumption of wine and dark red/blue colored fruits and polyphenol-rich fruits (e.g., pomegranate, blueberries, grapes), lemon balm, tart cherry powder, and L-Theanine for the two weeks leading up to the study (from the Screening visit V1 to baseline V2) and during the study.
8. Willing and able to avoid consumption of any cranberry juice, whole cranberries, and dried cranberries for the two weeks leading up to the study (from the Screening visit V1 to baseline V2) and during the study, excluding the study beverage.
9. Is willing to provide saliva samples.
10. Maintain current level of physical activity and dietary habits throughout the study.

Exclusion Criteria:

Participants that meet any of the following criteria will be excluded from the trial:

1. Has a known or suspected allergy to components of the investigational product (e.g., cranberries, tart cherry, lemon balm, L-theanine).
2. Uncontrolled blood pressure or untreated hypertension.
3. Consumes \>2 alcoholic beverages per day or \>14 per week.
4. Major chronic illness or health condition that might interfere with the study outcomes at the discretion of the study clinician or principal investigator.
5. Use of antidepressant, anxiolytic, Central Nervous System stimulant, antipsychotic, antimanic, anti-inflammatory (except for aspirin and non-steroidal anti-inflammatory drugs \[NSAIDS\]. Multivitamins, vaccines, gender affirming hormones, HIV prevention medications, allergy medications, topical steroids are allowed for inclusion.)
6. Individuals who smoke or use nicotine patches or gum or e-cigarettes, or marijuana (within the past 6 months).
7. Individuals who have experienced a stroke or a head injury with concussion, loss of consciousness or seizures.
8. History or clinical manifestation of any significant neurologic disorder in the opinion of the investigator and/or study clinician.
9. Any disease, that by the investigator's judgement, could interfere with the intestinal barrier function, including Celiac disease (Lactose intolerance or acid reflux are allowed for inclusion).
10. Participants may not be receiving treatment involving experimental drugs. If the participant has been in a recent experimental trial, these must have been completed not less than one month prior to this trial.
11. Desire and/or plans on changing current diet and/or exercise regime during the participation of this trial.
12. Individuals who are pregnant or lactating.
13. Individuals currently of childbearing potential, but not using an effective method of contraception, as determined by the investigator.
14. History of heavy caffeinated beverage consumption (\>400 mg caffeine/day - or 4 cups of coffee per day) within past 2 weeks prior to the Screening Visit (V1), or before their Baseline Visit (V2).

Primary outcomes:
measure: To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on attention.
timeFrame: 7 days
Secondary outcomes:
measure: To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on measures of focus.
timeFrame: 7 days
measure: To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on measures of alertness.
timeFrame: 7 days
measure: To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on measures of cognition (accuracy of performance).
timeFrame: 7 days
measure: To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on measures of cognition (speed of performance).
timeFrame: 7 days
measure: To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on mood.
timeFrame: 7 days
measure: To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on stress.
timeFrame: 7 days
Other outcomes:
measure: To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Proportion of Adverse Events).
timeFrame: 7 days
measure: To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Incidence of Adverse Events).
timeFrame: 7 days
measure: To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Incidence of Serious Adverse Events).
timeFrame: 7 days
measure: To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Blood Pressure).
timeFrame: 7 days
measure: To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Heart Rate).
timeFrame: 7 days
measure: To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Body Temperature).
timeFrame: 7 days
Locations:
city: Chicago
country: United States
facility: Atlantia Clinical Trials Ltd
state: Illinois
Study officials:
affiliation: Atlantia Clinical Trials Ltd.
name: Alice Eggleston, PA-C, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Yokogoshi H, Kobayashi M, Mochizuki M, Terashima T. Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res. 1998 May;23(5):667-73. doi: 10.1023/a:1022490806093.
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