A Study to Assess the Synergistic Effects of a Cranberry Beverage on Cognitive Function

Mood Clinical Trial

Official title:

A Randomized, Double-blinded, Placebo-controlled, Crossover Study, to Assess the Synergistic Effects of a Cranberry Beverage on Cognitive Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05008549
• Other study ID #: AFCRO-140
• Status: Completed
• Phase: N/A
• Start date: July 26, 2021
• Est. completion date: November 1, 2021

Study information

• Verified date: July 2023
• Source: Ocean Spray Cranberries, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: November 1, 2021
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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).

Related Conditions & MeSH terms

• Attention
• Mood

Intervention

Dietary Supplement:
• Cranberry Juice Product
The cranberry juice product contains 100 % cranberry juice (ingredients: water, cranberry juice concentrate) The cranberry juice + lemon balm extract product contains 100 % cranberry juice (ingredients: water, cranberry juice concentrate) + lemon balm extract (300 mg, Robertet Groupe) The cranberry juice + tart cherry juice product contains 100 % cranberry juice (ingredients: water, cranberry juice concentrate) + 3 g tart cherry powder (Cherry PURE) The cranberry juice + L-theanine product contains 100% cranberry juice (ingredients: water, cranberry juice concentrate) + 200 mg L-theanine (Suntheanine, Taiyo International) L-theanine + placebo product contains L-theanine (200 mg, Suntheanine, Taiyo International) + placebo (see 5.2.1) The placebo product contains water, dextrose, citric acid, malic acid, fumaric acid, natural flavor, Red #40, xanthan gum, Blue #1, gum Arabic, Reb M, Steviol glycosides, and ester gum.

Locations

Country	Name	City	State
United States	Atlantia Clinical Trials Ltd	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Ocean Spray Cranberries, Inc.	Atlantia Food Clinical Trials

Country where clinical trial is conducted

United States, 

References & Publications (8)

Chai SC, Jerusik J, Davis K, Wright RS, Zhang Z. Effect of Montmorency tart cherry juice on cognitive performance in older adults: a randomized controlled trial. Food Funct. 2019 Jul 17;10(7):4423-4431. doi: 10.1039/c9fo00913b. — View Citation

Kennedy DO, Little W, Scholey AB. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosom Med. 2004 Jul-Aug;66(4):607-13. doi: 10.1097/01.psy.0000132877.72833.71. — View Citation

Kennedy DO, Scholey AB, Tildesley NT, Perry EK, Wesnes KA. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav. 2002 Jul;72(4):953-64. doi: 10.1016/s0091-3057(02)00777-3. — View Citation

Lamport DJ, Williams CM. Polyphenols and Cognition In Humans: An Overview of Current Evidence from Recent Systematic Reviews and Meta-Analyses. Brain Plast. 2021 Feb 9;6(2):139-153. doi: 10.3233/BPL-200111. — View Citation

Scholey A, Gibbs A, Neale C, Perry N, Ossoukhova A, Bilog V, Kras M, Scholz C, Sass M, Buchwald-Werner S. Anti-stress effects of lemon balm-containing foods. Nutrients. 2014 Oct 30;6(11):4805-21. doi: 10.3390/nu6114805. — View Citation

Travica N, D'Cunha NM, Naumovski N, Kent K, Mellor DD, Firth J, Georgousopoulou EN, Dean OM, Loughman A, Jacka F, Marx W. The effect of blueberry interventions on cognitive performance and mood: A systematic review of randomized controlled trials. Brain B — View Citation

Williams JL, Everett JM, D'Cunha NM, Sergi D, Georgousopoulou EN, Keegan RJ, McKune AJ, Mellor DD, Anstice N, Naumovski N. The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Proportion of Adverse Events).	Proportion of Adverse Events per treatment phase by product causality.	7 days
Other	To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Incidence of Adverse Events).	Incidence of mild, moderate, and severe Adverse Events per treatment phase by product causality.	7 days
Other	To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Incidence of Serious Adverse Events).	Incidence of Serious Adverse Events per treatment phase by product causality.	7 days
Other	To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Blood Pressure).	Change in Blood Pressure from Baseline to each subsequent visit (V3-8).	7 days
Other	To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Heart Rate).	Change in Heart Rate from Baseline to each subsequent visit (V3-8).	7 days
Other	To evaluate in healthy adults the safety and tolerability of 7-day consumption of cranberry beverages compared to placebo (Body Temperature).	Change in Body Temperature from Baseline to each subsequent visit (V3-8).	7 days
Primary	To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on attention.	Change in Accuracy of Attention and Change in Speed of Attention composite scores outcomes from Baseline to each treatment phase (V3-8), assessed using the COMPASS cognitive assessment tool.	7 days
Secondary	To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on measures of 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.	7 days
Secondary	To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on measures of alertness.	Change in Alertness scores outcomes from Baseline to each treatment phase (V3-8), assessed using the self-rated Alertness Visual Analogue Scale in the COMPASS cognitive assessment tool.	7 days
Secondary	To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on measures of cognition (accuracy of performance).	Change in Accuracy of Performance composite scores outcomes from Baseline to each treatment phase (V3-8), assessed using the COMPASS cognitive assessment tool.	7 days
Secondary	To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on measures of cognition (speed of performance).	Change in Speed of Performance composite scores outcomes from Baseline to each treatment phase (V3-8), assessed using the COMPASS cognitive assessment tool.	7 days
Secondary	To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on mood.	Change in Total Mood Disturbance scores from Baseline to each subsequent visit (V3-8), assessed using the Profile of Mood States-Short Questionnaire.	7 days
Secondary	To evaluate in healthy adults the effect of 7-day consumption of cranberry beverages compared to placebo on stress.	Change in salivary cortisol from Baseline to each treatment phase (V3-8).	7 days