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

Sponsor

University of Reading (Other)

Overall Status

Recruiting

CT.gov ID

NCT05422599

Collaborator

Naturex (Other)

108

Enrollment

Location

Arms

12.8

Anticipated Duration (Months)

8.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Sleep Disturbance Mood Disturbance	Dietary Supplement: Lemon balm Dietary Supplement: Placebo	N/A

Detailed Description

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Between and within groups modelBetween and within groups model

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Double-blind

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

May 5, 2022

Anticipated Primary Completion Date :

May 30, 2023

Anticipated Study Completion Date :

May 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lemon balm 300mg Lemon balm and Maltodextrin	Dietary Supplement: Lemon balm 300mg Lemon balm and Maltoxdextrin capsules Other Name: Melissa Officinalis L.
Placebo Comparator: Placebo Placebo	Dietary Supplement: Placebo 300mg Maltodextrin capsules

Arm

Intervention/Treatment

Experimental: Lemon balm

300mg Lemon balm and Maltodextrin

Dietary Supplement: Lemon balm

300mg Lemon balm and Maltoxdextrin capsules Other Name: Melissa Officinalis L.

Placebo Comparator: Placebo

Placebo

Dietary Supplement: Placebo

300mg Maltodextrin capsules

Outcome Measures

Primary Outcome Measures

Pittsburgh Sleep Quality Index (PSQI) [4 weeks]
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.

Secondary Outcome Measures

Combined Sleep Diary and Research-Grade Actiwatch Sleep-Wake Patterns [Continuous over 4 weeks]
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.
Diurnal Salivary Cortisol and Melatonin Patterns [4 weeks]
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.
Gut Microbiota Changes [4 weeks]
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.
Insomnia Severity Index (ISI) [4 weeks]
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.
Leeds Sleep Evaluation Questionnaire (LSEQ) [4 weeks]
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.
Perceived Stress Scale (PSS) [4 weeks]
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.
Positive affect as measured by PANAS-X [4 weeks]
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.
Positive affect as measured by PANAS-NOW [4 weeks]
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.
Negative affect as measured by PANAS-X [4 weeks]
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.
Negative affect as measured by PANAS-NOW [4 weeks]
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.
Depression, Anxiety and Stress Scale - 21 items (DASS-21) [4 weeks]
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).
Flinders Fatigue Scale (FFS) [4 weeks]
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.
Vivascentz(TM) Metric [4 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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