Clinical trial NCT06183372: Enhancement of Calmness and Mood Following Acute Lemon Balm Supplementation During Cognitive Demand in Adults
Official title: A Randomised Double-blind Placebo-controlled Acute Trial of Encapsulated Lemon Balm Efficacy and Tolerance on Calmness and Mood During Periods of Cognitive Demand
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stress
Mood Disturbance
Keywords: Calmness
Subject Satisfaction
Mood enhancement
Relaxation
Lemon Balm
Melissa Officinalis
Herbal Psychotropic
Cognitive demand
Memory
Attention
Executive Function
Lead sponsor: University of Reading
Sponsor class: OTHER
Collaborators: name: Naturex
First posted: 2023-12-27
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Between- and within-groups (mixed) model
Primary purpose: PREVENTION

Brief summary: This study aims to investigate the effect of a single dose (300mg) of encapsulated aqueous lemon balm extract on measures of calmness and mood during periods of cognitive demand over the course of the day in healthy adults aged 18-40 years with moderate stress (PSS entry between 14 to 26).

Detailed description: Cognitive overload can be a common occurrence in an information saturated world (Eppler et al., 2008; Graf et al., 2021; Pass et al., 2004), and chronic cognitive overload is considered an initiating step in the emergence of various physical and emotional health concerns, likely due to high processing demands on the working memory neural system (Graf et al., 2021). Over time, psychological and physiological stress may arise, however current chemical interventions may be unsuitable for those experiencing mild-to-moderate levels of stress (Ghazizadeh et al., 2021). Indeed, long-term use of psychotropic medicines have previously been associated with a worsening of psychological symptoms (Bertuccioli et al., 2022). Therefore, identifying interventions for those experiencing mild-to-moderate stress will have strong public health implications for the prevention or reduction of symptoms. In addition, an opportunity for dietary supplementation as an over-the-counter option for those who do not wish to take chemical interventions is becoming a popular choice (Ghazizadeh et al., 2021; Bertuccioli et al. 2022).

The current study will employ a parallel, double-blind, randomised placebo-controlled trial, assessing the effect of a single dose intervention of lemon balm extract (or matched placebo) in young-to-middle-aged adults with moderate levels of perceived stress. Subjects will be pre-screened to determine eligibility using the perceived stress questionnaire, where scores between 14 to 26 are indicative of moderate stress, to provide a total of 130 participants. The study comprises a familiarisation visit followed by an acute test day at the Nutritional Psychology Unit based at the University of Reading. The familiarisation visit will allow participants to practice the cognitive battery, complete calmness and mood measures, and provide information on habitual diet (Epic-Norfolk FFQ) and general health and lifestyle patterns to confirm eligibility. On the acute test day, subjective calmness and mood ratings will be recorded at various timepoints throughout the day, beginning with an initial baseline measurement (0h), and then 1h, 3h and 5h after consuming an acute dose of lemon balm extract (300mg) or a matched placebo. At these same timepoints, a computer-based cognitive battery will be completed, consisting of several tasks assessing domains of executive function, attention and memory. On the acute test day participants will arrive fasted and will be provided with a standardised breakfast (two croissants and a glass of water) to be consumed prior to 0h baseline measures. A standardised lunch (cheese sandwich, packet of crisps, and water) will also be provided after the 3h timepoint.

Eligibility criteria: Inclusion Criteria:

* Healthy, between 18-40 years old
* Moderate Stress problems (PSS between 14 to 26)
* No alcohol or vigorous activity 24h before the task
* No coffee/caffeine intake 12h before the visits
* Non-smokers or Must not smoke during 7 days prior to the trial: Includes smoking tobacco, vaping nicotine, using nicotine replacement products, or occasional social smoking.
* Willingness to wash out for food supplementation during 2 weeks before the experiment

Exclusion Criteria:

* Use medications that may affect the outcome
* Any long-term psychological or physiological health conditions
* Have any allergic reactions to ingredients in the capsules
* Have a BMI greater than or equal to 30
* Have any allergic reactions to ingredients in the capsules
* Consumed more than 400 mg of caffeine (\>5 expresso) per day in the past 2 weeks
* Have used any psychotropic medications, stimulants, cannabis, non-registered drug products, or illicit substances in the past 2 weeks, were at risk of drug or alcohol abuse
* Taking any dietary supplements which they are unwilling to stop for the duration of the study
* Have sleep disorders or are taking sleep aid medication
* Fail to demonstrate adequate minimal performance on lab, computer-based cognitive tasks
* Have a diagnosed neurological condition, or learning/behavioural or neurodevelopmental differences (e.g. dyslexia, autism, ADHD).

Primary outcomes:
measure: Calmness 9-point Likert Scale
timeFrame: Baseline
measure: Calmness 9-point Likert Scale
timeFrame: 5 hours following intervention
Secondary outcomes:
measure: Fatigue 9-point Likert Scale
timeFrame: Baseline
measure: Fatigue 9-point Likert Scale
timeFrame: 5 hours following intervention
measure: Subject Satisfaction 4-point Category Scale
timeFrame: 1 hour following intervention
measure: Subject Satisfaction 4-point Category Scale
timeFrame: 3 hours following intervention
measure: Subject Satisfaction 4-point Category Scale
timeFrame: 5 hours following intervention
measure: Visual Analogue Stress Scale
timeFrame: Baseline
measure: Visual Analogue Stress Scale
timeFrame: 1 hour following intervention
measure: Visual Analogue Stress Scale
timeFrame: 3 hours following intervention
measure: Visual Analogue Stress Scale
timeFrame: 5 hours following intervention
measure: Bond-Lader 16-item Visual Analogue Stress Scale
timeFrame: Baseline
measure: Bond-Lader 16-item Visual Analogue Stress Scale
timeFrame: 1 hour following intervention
measure: Bond-Lader 16-item Visual Analogue Stress Scale
timeFrame: 3 hours following intervention
measure: Bond-Lader 16-item Visual Analogue Stress Scale
timeFrame: 5 hours following intervention
measure: Immediate Word Recall (Rey Auditory Verbal Learning Task)
timeFrame: Baseline
measure: Immediate Word Recall (Rey Auditory Verbal Learning Task)
timeFrame: 1 hour following intervention
measure: Immediate Word Recall (Rey Auditory Verbal Learning Task)
timeFrame: 3 hours following intervention
measure: Immediate Word Recall (Rey Auditory Verbal Learning Task)
timeFrame: 5 hours following intervention
measure: Delayed Word Recall (Rey Auditory Verbal Learning Task)
timeFrame: Baseline
measure: Delayed Word Recall (Rey Auditory Verbal Learning Task)
timeFrame: 1 hour following intervention
measure: Delayed Word Recall (Rey Auditory Verbal Learning Task)
timeFrame: 3 hours following intervention
measure: Delayed Word Recall (Rey Auditory Verbal Learning Task)
timeFrame: 5 hours following intervention
measure: Modified Attention Network Task (with two blocks of Serial 3's)
timeFrame: Baseline
measure: Modified Attention Network Task (with two blocks of Serial 3's)
timeFrame: 1 hour following intervention
measure: Modified Attention Network Task (with two blocks of Serial 3's)
timeFrame: 3 hours following intervention
measure: Modified Attention Network Task (with two blocks of Serial 3's)
timeFrame: 5 hours following intervention
measure: Task Switching Test
timeFrame: Baseline
measure: Task Switching Test
timeFrame: 1 hours following intervention
measure: Task Switching Test
timeFrame: 3 hours following intervention
measure: Task Switching Test
timeFrame: 5 hours following intervention
measure: Rapid Visual Information Processing Task
timeFrame: Baseline
measure: Rapid Visual Information Processing Task
timeFrame: 1 hour following intervention
measure: Rapid Visual Information Processing Task
timeFrame: 3 hours following intervention
measure: Rapid Visual Information Processing Task
timeFrame: 5 hours following intervention
measure: Paced Auditory Serial Addition Task
timeFrame: Baseline
measure: Paced Auditory Serial Addition Task
timeFrame: 1 hour following intervention
measure: Paced Auditory Serial Addition Task
timeFrame: 3 hours following intervention
measure: Paced Auditory Serial Addition Task
timeFrame: 5 hours following intervention
measure: Systolic Blood Pressure
timeFrame: Baseline
measure: Systolic Blood Pressure
timeFrame: 1 hour following intervention
measure: Systolic Blood Pressure
timeFrame: 3 hour following intervention
measure: Systolic Blood Pressure
timeFrame: 5 hour following intervention
measure: Diastolic Blood Pressure
timeFrame: Baseline
measure: Diastolic Blood Pressure
timeFrame: 1 hour following intervention
measure: Diastolic Blood Pressure
timeFrame: 3 hours following intervention
measure: Diastolic Blood Pressure
timeFrame: 5 hours following intervention
measure: Heart Rate
timeFrame: Baseline
measure: Heart Rate
timeFrame: 1 hour following intervention
measure: Heart Rate
timeFrame: 3 hours following intervention
measure: Heart Rate
timeFrame: 5 hours following intervention
Other outcomes:
Locations:
city: Reading
country: United Kingdom
facility: University of Reading
Study officials:
affiliation: University of Reading
name: Claire M Williams
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bertuccioli A, Cardinali M, Di Pierro F, Magi S, Zonzini G. A Practical Perspective on the Use of Botanicals During the COVID-19 Pandemic: From Proven to Potential Interactions. J Med Food. 2022 Jan;25(1):1-11. doi: 10.1089/jmf.2021.0062. Epub 2021 Nov 17.
citation: Ghazizadeh J, Sadigh-Eteghad S, Marx W, Fakhari A, Hamedeyazdan S, Torbati M, Taheri-Tarighi S, Araj-Khodaei M, Mirghafourvand M. The effects of lemon balm (Melissa officinalis L.) on depression and anxiety in clinical trials: A systematic review and meta-analysis. Phytother Res. 2021 Dec;35(12):6690-6705. doi: 10.1002/ptr.7252. Epub 2021 Aug 27.