A Study to Evaluate the Efficacy of VL-NL-02 on Sleep Quality.

Study Overview
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Brief Summary
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The goal of this clinical trial is to study the impact of VL-NL-02 in improving sleep quality, restorative sleep complaints, quality of life, stress levels, and sleep stages. 48 participants are expected to be randomized in a ratio of 1:1 to receive either VL-NL-02 or placebo and will be assigned a unique randomization code. Each group will have at least 20 completed participants after accounting for a dropout/withdrawal rate of 17%. The intervention duration for all the study participants is 21 days. Participants will be asked to fill multiple questionnaires to assess sleep quality and mood imbalance.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel Study to Evaluate the Efficacy of VL-NL-02 on Sleep and Mood.

Conditions
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Mood and Sleep Quality

Intervention / Treatment
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* Dietary Supplement: VL-NL-02
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals aged between ≥ 18 and ≤ 50 years with a moderately active lifestyle as assessed International Physical Activity Questionnaire - Short form (IPAQ - SF) Individuals with mild to moderate sleeping issues as assessed by an ISI score of ≥ 8 and ≤ 21 Individuals with a history of at least 3 episodes of sleep disturbances in the last month. Individuals with a Fasting Blood glucose (FBG) ≤ 125 mg/dl All individuals who are free from use of sleeping pills for at least 4 weeks before screening Individuals with normal levels of laboratory parameters: Liver profile, Lipid profile and kidney profile. [Refer to section 3.7.3 for details on parameters included and reference ranges.] Individuals with no more than once per week use of pain-relieving medications. Individuals with body mass index between ≥18 and ≤ 30 kg/m2. Typical bedtime between 9 PM and 11 PM. Individuals willing to abstain from digital activity 3 hours prior to the PSG analysis Willing to maintain current dietary pattern, activity level, and stable body weight for the duration of the study, and refrain from any drastic lifestyle changes. Exclusion Criteria: FBG > 125 mg/dl Individuals diagnosed with hypertension. Individuals having a systolic blood pressure ≥140 mm Hg and diastolic blood pressure ≥ 90 mm Hg. Individuals diagnosed with Type I and Type II Diabetes Mellitus. Sleep disorder is secondary to another health problem such as restless leg syndrome, post-operative state etc. Individuals diagnosed with insomnia. Consumption of hypnotic drugs (<3 months before inclusion) Individuals taking any other sleep promoting supplements and are unwilling to stop taking those supplements for the duration of the study period Individuals with history of sleepwalk Individuals who have bad dreams 2 or more times a week. Individuals who are inclined to the lifestyle factors - such as jet lag, night workers and rotational shift work. Individuals who currently, or in the past 6 months suffered from any mental-health disorder Individuals who were taking psychotropic medication, herbal preparation, antidepressants, steroids, antihistamines, narcotics or any other illicit drugs in the last three months. Individuals diagnosed with chronic medical conditions - such as heart problems, Gastro-intestinal, hepatic, respiratory, psychiatric, kidney, or cardiovascular disorder (<3 months before inclusion), and chronic pain since last 6 months. Recent (within 3 months before inclusion) change in lifestyle (food, sport and drug). Individuals who are regular smokers and/or consume any form of tobacco. Addiction, history of addiction, and/or substance abuse (tobacco, nicotine etc.). Heavy drinkers as defined by: For men, consuming more than 4 drinks on any day or more than 14 drinks/week For women, consuming more than 3 drinks on any day or more than 7 drinks/week Exaggerated consumption of tea (≥500 mL per day), coffee (≥400 mL per day), or energy drink (≥250 mL per day), Individuals on dietary supplements Pregnant or lactating woman, Lifestyle habits which would modify the wake-sleep rhythm or which was expected to be modified during the study period (e.g., night work) Known allergy to mushroom.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, double-blind, placebo-controlled trial.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VL-NL-02<br>Two capsules to be taken 45±10 mins before sleep (after dinner) for 21 days. | Dietary Supplement: VL-NL-02<br>* Two capsules to be taken 45±10 mins before sleep (after dinner) for 21 days<br>|
| Placebo Comparator: Placebo<br>Two capsules to be taken 45±10 mins before sleep (after dinner) for 21 days. | Dietary Supplement: Placebo<br>* Two capsules to be taken 45±10 mins before sleep (after dinner) for 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of Vl-NL-02 on sleep quality using the Insomnia Severity Index (ISI). | The Insomnia Severity Index has seven questions that indicates insomnia without clinical significance. The scores of 0-7 determines no clinically significant insomnia, 8-14 determines sub threshold insomnia, 15-21 has moderate severity which determines clinical insomnia and lastly 22-28 has severe insomnia. For each question, participant will be asked to circle or mark the number that best correlates with their sleep quality in the past two weeks. An increase in score will determine the severity of the insomnia. | Day 1 of intervention | 
| To assess the efficacy of Vl-NL-02 on sleep quality using the Insomnia Severity Index (ISI). | The Insomnia Severity Index has seven questions that indicates insomnia without clinical significance. The scores of 0-7 determines no clinically significant insomnia, 8-14 determines sub threshold insomnia, 15-21 has moderate severity which determines clinical insomnia and lastly 22-28 has severe insomnia. For each question, participant will be asked to circle or mark the number that best correlates with their sleep quality in the past two weeks. An increase in score will determine the severity of the insomnia. | Day 11 of intervention | 
| To assess the efficacy of Vl-NL-02 on sleep quality using the Insomnia Severity Index (ISI). | The Insomnia Severity Index has seven questions that indicates insomnia without clinical significance. The scores of 0-7 determines no clinically significant insomnia, 8-14 determines sub threshold insomnia, 15-21 has moderate severity which determines clinical insomnia and lastly 22-28 has severe insomnia. For each question, participant will be asked to circle or mark the number that best correlates with their sleep quality in the past two weeks. An increase in score will determine the severity of the insomnia. | Day 22 of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess impact of VL-NL-02 on Mood using Brief Mood Introspection Scale (BMIS) | It is a mood scale consisting of 16 mood adjectives to which a person responds. Four sub scores can be computed from the BMIS: Pleasant-Unpleasant, Arousal-Calm, Positive-Tired and Negative-Relaxed Mood. | Day 1, 11 and 22 of intervention | 
| To assess impact of VL-NL-02 on Dream as assessed by Dream and Sleep Emotions and Anxiety (DSEA) Questionnaire | The DSEA questionnaire has two subscales: Sleep anxiety and Dream emotional scale. | Day 1, 11 and 22 of intervention | 
| To assess impact of VL-NL-02 on Restorative sleep by using Restorative Sleep Questionnaire - Weekly Version (RSQ-W) questionnaire | RSQ-W is a validated scale for measuring refreshing quality of sleep. It has 9 items with answers scaled from 1 to 5. The questionnaire asks about how one felt after waking up and starting the day during the past seven days. | Day 1, 11 and 22 of intervention | 
| To assess impact of VL-NL-02 on Quality of life using RAND Short form (SF)-36 | The SF-36 includes multi-item scales to measure the following 8 dimensions (refer 15.2 for questionnaire): PF- Physical functioning (10 items in question 3) RP- Role limitations due to physical health problems (4 items in question 4) BP- Overall body pain (questions 7 and 8) SF- Social functioning (questions 6 and 10) MH - General mental health, covering psychological distress and well-being (5 items: questions 9 b, c, d, f and h) RE- Role limitations due to emotional problems (questions 5 a, b and c) VT- Vitality, energy or fatigue (4 items: questions 9 a, e, g and i) GH- General health perceptions (5 items: questions 1 and 11 a to d) | Day 1, 11 and 22 of intervention | 
| To assess impact of VL-NL-02 on Improvement in deep sleep and Rapid eye movement (REM) sleep stages by Polysomnography | Polysomnography refers to a systematic process used to collect physiologic parameters during sleep. Sleep stage scoring and detection of arousals for each 30-s epoch will be performed visually according to standard AASM procedures. | Day 0, 10 and 21 of intervention | 
| To assess impact of VL-NL-02 on Levels of salivary cortisol immediately after awakening | Normal ranges for cortisol are: Morning hours 8 10 a.m.: < 19.1 nmol/L (< 0.690 μg/dL) Afternoon hours 2:30-3:30 p.m.: < 11.9 nmol/L (< 0.430 μg/dL) | Day 1 and 22 of Intervention | 
| To assess impact of VL-NL-02 on Levels of serum serotonin | The normal range is 50 to 200 ng/mL (0.28 to 1.14 µmol/L) in healthy individuals | Day 1 and 22 of Intervention | 
| To assess impact of VL-NL-02 on Levels of urinary melatonin | The highest levels of melatonin are recorded from 3am onwards with a value of 47.35 pg/ml | Day 1 and 22 of Intervention | 
| To assess impact of VL-NL-02 on Levels of serum Brain Derived Neurotrophic Factor (BDNF) |  | Day 1 and 22 of Intervention |