Enhancement of Sleep Quality and Mood Following Supplementation With Lemon Balm in an Adult Population (Lemslp)

Study Overview
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Brief Summary
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This study aims to investigate the effect of a 4-week dietary intervention of 300mg encapsulated aqueous lemon balm extract on measures of sleep quality, mood and well-being, alongside relevant biomarkers of circadian rhythms in healthy adults aged 18-40 years with mild sleep problems (PSQI entry of 5 and above). Three visits to the university alongside completing some home tests involving self-test stool, saliva and mood tests and wearing an wrist-secured actiwatch over 4-weeks whilst recording a daily sleep diary will be monitored to estimate sleep changes. Mood ratings, stool and saliva biomarkers will serve as a proxy to sleep improvement.

Detailed Description
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A randomised, double-blind, placebo-controlled, parallel-design study assessing the effect of a 4-week intervention of lemon balm extract (or matched placebo) in young to middle-age adults with mild sleep problems. A total of 108 participants will be randomly assigned to either 300 mg lemon balm extract or a matched placebo capsule consumed nightly before retiring to bed. The severity of sleep problems, depression, anxiety, perceived stress, quality of life and well-being will be measured at baseline and after 4 weeks of daily consumption. In addition, we will assess changes in microbiota and saliva neurohormone profiles at baseline and after 4 weeks of treatment. Entry to the study to determine eligibility involves a sleep quality questionnaire (PSQI) score of 5 and above. The study comprises of a familiarisation visit and then two test days at the Nutritional Psychology Unit based at the University of Reading where primary sleep (PSQI), and exploratory measures of sleep (ISI, LSEQ) and mood (PANAS, Vivascentz(TM), FFS, PSS, DASS-21) tests will be completed. The screening visit will further assess habitual diet (Epic-Norfolk FFQ), and general health and lifestyle patterns to confirm eligibility. Participants will then continuously wear an wrist-secured actiwatch whilst recording a daily sleep diary to estimate sleep changes over the 4-week period. In addition, some further exploratory tests will be completed by participants from home 24h before baseline and 24h before post-intervention (saliva, stool, PANAS-X).

Official Title
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A Randomised Double-blind Placebo-controlled Trial on Encapsulated Lemon Balm Efficacy and Tolerance on Sleep Quality Changes, and Mood and Wellbeing Effects Using Objective and Subjective Measures

Conditions
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Sleep Disturbance, Mood Disturbance

Intervention / Treatment
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* Dietary Supplement: Lemon balm
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, between18-40 years old Mild Sleep problems (PSQI less than or equal to 5) Willingness to provide stool and saliva samples, wear an actiwatch and complete a nightly sleep diary. 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 Are vegetarian Taking any dietary supplements which they are unwilling to stop for the duration of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Between and within groups model
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lemon balm<br>300mg Lemon balm and Maltodextrin | Dietary Supplement: Lemon balm<br>* 300mg Lemon balm and Maltoxdextrin capsules Other Name: Melissa Officinalis L.<br>|
| Placebo Comparator: Placebo<br>Placebo | Dietary Supplement: Placebo<br>* 300mg Maltodextrin capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pittsburgh Sleep Quality Index (PSQI) | A validated measure of sleep assessing qualities and patterns within the last month of sleep habits in adults. Seven components of sleep (quality, latency, duration, efficiency, disturbance, use of sleep medication, daytime dysfunction) will be summed to achieve a global PSQI score ranging from 0 to 21 points, where scores above 5 indicates sleep problems. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Sleep Diary and Research-Grade Actiwatch Sleep-Wake Patterns | Passive motion tracking of sleep-wake patterns (heart rate variability) will be recorded via a wrist-worn research-grade actiwatch. The actiwatches will be secured on the participant's wrist throughout the study period. To cross-examine the actiwatch data, an in-house standardised daily sleep diary will measure sleep quality, sleep duration and sleep latency (how many times awoken during sleep time) (Carney et al., 2012; Orchard et al., 2020) where meaningful sleep outcomes will be manually inputted into actiwatch software at the end of sleep monitoring, as per standard practice in sleep research. | Continuous over 4 weeks | 
| Diurnal Salivary Cortisol and Melatonin Patterns | Determination of changes in circadian sleep-wake patterns after 4-weeks daily 300mg lemon balm treatment by assessing diurnal sleep neurohormones, melatonin and cortisol. Changes in melatonin and cortisol will be assessed using 12 salivary self-test sampling kits taken in two windows (6 samples per window), within 24h before baseline day and within 24h before post-intervention day. For each test day, two samples will be taken first thing in the morning, 11am, 5pm and a final two samples in the evening. Sleep neurohormones will then be assessed against subjective sleep scores. | 4 weeks | 
| Gut Microbiota Changes | Examination of gut responses to mood and sleep physiology changes after 4-weeks daily 300mg lemon balm treatment by assessing changes in faecal microbiota levels. Two samples will be collected over the entire study. Microbiome diversity will be determined using self-test stool sampling kits taken in two windows, within 24h before baseline day and within 24h before post-intervention day. Faecal microbiota will then be compared to subjective sleep and mood scores. | 4 weeks | 
| Insomnia Severity Index (ISI) | A validated 7-item instrument designed to assess the nature, severity and impact of both nighttime and daytime components of insomnia within the last month. The scale ranges from 0 to 28 where higher scores indicate more severe insomnia. | 4 weeks | 
| Leeds Sleep Evaluation Questionnaire (LSEQ) | A 10-item self-report slider scale to evaluate ease of getting to sleep, sleep quality, ease of waking and behaviour following wakefulness. Higher scores indicate better sleep quality. | 4 weeks | 
| Perceived Stress Scale (PSS) | A validated 10-item questionnaire to measure levels of perceived stress. The scale ranges from 0 to 40 points with higher scores indicating greater stress levels. | 4 weeks | 
| Positive affect as measured by PANAS-X | General positive affect for assessing trait mood over the past month will be calculated by adding the values of 10 positive items in correspondence with the original PANAS, ranging from 0-50 where higher scores indicate positive affect. In addition, the expanded Positive and Negative Affect Schedule-X will assess higher order scales Surprise, Joviality,Self-Assurance, Attentiveness, and Serenity and these collective scores combined with general positive affect range from 0 to 170 points, where higher scores indicate better mood. | 4 weeks | 
| Positive affect as measured by PANAS-NOW | General positive affect for assessing transient mood as the respondent feels in the present moment will be calculated by adding the values of 10 positive items. Scores range from 0-50 points where higher scores indicate positive affect. | 4 weeks | 
| Negative affect as measured by PANAS-X | General positive affect for assessing trait mood over the past month will be calculated by adding the values of 10 negative items in correspondence with the original PANAS, ranging from 0-50 where higher scores indicate negative affect. In addition, the expanded Positive and Negative Affect Schedule-X will assess higher order scales Fear, Sadness, Guilt, Hostility, Shyness, Fatigue and these collective scores combined with general negative affect range from 0 to 170 points, where higher scores indicate worse mood. | 4 weeks | 
| Negative affect as measured by PANAS-NOW | General negative affect for assessing transient mood as the respondent feels in the present moment will be calculated by adding the values of 10 negative items, ranging from 0-50 where higher scores indicate negative affect. | 4 weeks | 
| Depression, Anxiety and Stress Scale - 21 items (DASS-21) | A validated 21-item measure to assess the severity of depression, anxiety and stress components, with 7 items per component. Each item is scored from 0-3 where higher scores indicate higher levels of distress in anxiety (scores range from 0 to >20), depression (0 to >28) and/or stress (0 to >34). | 4 weeks | 
| Flinders Fatigue Scale (FFS) | A self-report 7-item questionnaire to assess perception of frequency and severity of fatigue over the past 2 weeks. Global fatigue scores range from 0 to 31, where higher scores indicate greater fatigue. | 4 weeks | 
| Vivascentz(TM) Metric | An in-house Givaudan wellbeing metric, and patent approved (WO2020165463). This 18-item scale measures transient feelings in the present moment assessing 9 positive and 9 negative attributes (reverse scored) to contribute to overall wellbeing scores. Scores range from 0 to 180, where higher scores indicate higher wellbeing. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep Quality, Sleep Onset Latency, Sleep Duration, Lemon Balm, Melissa Officinalis, Herbal Psychotropic, Sleep Diaries, Actiwatches, PSQI, Gut-Brain Axis Microbiota, Wellbeing, Antidepressant, Anxiolytic, Cognitive-Enhancing, Salivary Analytes, Melatonin, Cortisol