The Safety and Efficacy of AlphaWave® L-Theanine on Adults Who Experience Moderate Stress on a Regular Basis

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy of AlphaWave® L-Theanine on stress among adults who experience moderate stress on a regular basis. The difference in change in stress as assessed by salivary cortisol from baseline at Days 14 and 28 will be compared between AlphaWave® L-Theanine and Placebo groups. Additionally, the safety and tolerability of AlphaWave® L-Theanine, as compared to placebo, will be measured by the occurrence of an/or changes in pre-emergent and post-emergent adverse events (AEs).

Official Title
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A Randomized, Double-blind, Placebo Controlled, Parallel Clinical Trial to Investigate the Efficacy of AlphaWave® L-Theanine on Adults Who Experience Moderate Stress on a Regular Basis

Conditions
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Stress

Intervention / Treatment
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* Dietary Supplement: AlphaWave® L-Theanine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between 18 and 65 years of age, inclusive Female participant is not of child-bearing potential, defined as females who have undergone a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, bilateral tubal ligation, total endometrial ablation) or have been post-menopausal for at least 1 year prior to screening Or, Females of child-bearing potential must have a negative baseline urine pregnancy test and agree to use a medically approved method of birth control for the duration of the study. All hormonal birth control must have been in use for a minimum of three months. Acceptable methods of birth control include: Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System) Double-barrier method Intrauterine devices Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s) Vasectomy of partner at least 6 months prior to screening Individuals with moderate stress as determined by a score of 14 - 26 on the Perceived Stress Scale Agrees to maintain current sleep schedule throughout study Must have a high school diploma or equivalent and basic computer skills Agrees to avoid high caffeine consumption (examples include but not limited to no more than 2 cups/day of caffeinated coffee or tea) Agrees to refrain from vigorous physical activity 24-hr prior to study visits Agrees to maintain current lifestyle as much as possible including current sleep schedule until the end of the study Willingness to complete questionnaires, records and diaries associated with the study, and to complete all clinic visits Provided voluntary, written, informed consent to participate in the study Healthy as determined by medical history, laboratory results, and as assessed by the QI Exclusion Criteria: Women who are pregnant, breastfeeding, or planning to become pregnant during the course of the trial Participants who have a known allergy to the Investigational Product (IP) or Placebo active or inactive ingredients Current employment that calls for rotating shift work or shift work that will disrupt normal circadian rhythm in the last 3 weeks Travelled across 1 or more time zones in the 3 weeks prior to run-in and/or is anticipating more travel Self-reported diagnosis with a stress or sleep disorder as assessed by the QI Self-reported diagnosis of a neuropsychiatric and/or cognitive impairment as assessed by the QI Self reported colour-blindness Type I or Type II Diabetes Unstable metabolic disease or chronic diseases as assessed by the QI Current or history of any significant disease of the gastrointestinal tract as assessed by the QI Unstable hypertension. Treatment on a stable dose of medication for at least 3 months will be considered by the QI Significant cardiovascular event in the past 6 months as assessed by the QI Major surgery in the past 3 months or individuals who have planned surgery during the course of the trial. Participants with minor surgery will be considered on a case-by-case basis by the QI Cancer, except skin basal cell carcinoma completely excised with no chemotherapy or radiation with a follow up that is negative. Volunteers with cancer in full remission for more than five years after diagnosis are acceptable Individuals with an autoimmune disease or are immune-compromised History of or current diagnosis with kidney and/or liver diseases as assessed by the QI on a case-by-case basis, with the exception of history of kidney stones symptom-free for 6 months Self reported current or pre-existing thyroid condition. Treatment on a stable dose of medication for at least 3 months will be considered by the QI Self reported blood/bleeding disorders that will have an effect on safety outcomes as assessed by the QI Self-reported alcohol or drug abuse within the last 12 months High alcohol intake (>2 standard drinks per day) Use of medicinal cannabinoid products, as assessed by the QI Chronic use of cannabinoid products (≥2 times/week) and is unwilling to stop use for the duration of the study. Occasional use to be assessed by QI on a case-by-case basis Use of tobacco and nicotine-containing products within 60 days of baseline and during the study period Current use of prescribed medications which may affect stress, sleep, cognition, and/or mood (see Section 7.3.1) Current use of over-the-counter medications, supplements, foods, and/or drinks which may affect stress, sleep, cognition, and/or mood unless willing to undergo the appropriate washout (see Section 7.3.2) Clinically significant abnormal laboratory results at screening as assessed by the QI Blood donation 30 days prior to baseline, during the study, or a planned donation within 30 days of the last study visit Participation in other clinical research studies 30 days prior to baseline, as assessed by the QI Individuals who are unable to give informed consent Any other condition or lifestyle factor, that, in the opinion of the QI, may adversely affect the participant's ability to complete the study or its measures or pose significant risk to the participant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AlphaWave® L-Theanine<br>Participants will be instructed to take one capsule twice daily, once in the morning and once in the evening with water with or without food, starting on Day 1. If a dose is missed participants are instructed to take the missed dose immediately once noticed unless it is noticed within two hours of taking their next dose in which case, participants are instructed to document the missed dose and continue with their regular dosing schedule. Participants will be advised not to exceed 3 capsules daily. | Dietary Supplement: AlphaWave® L-Theanine<br>* One capsule of AlphaWave® L-Theanine will be taken twice daily for 28 days.<br>|
| Placebo Comparator: Placebo<br>Participants will be instructed to take one capsule twice daily, once in the morning and once in the evening with water with or without food, starting on Day 1. If a dose is missed participants are instructed to take the missed dose immediately once noticed unless it is noticed within two hours of taking their next dose in which case, participants are instructed to document the missed dose and continue with their regular dosing schedule. Participants will be advised not to exceed 3 capsules daily. | Other: Placebo<br>* One capsule of Placebo will be taken twice daily for 28 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in change in stress as assessed by salivary cortisol from baseline at Days 14 and 28 between AlphaWave® L-Theanine and Placebo. |  | Day 0, day 14, day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in change in stress as measured by the Perceived Stress Scale (PSS) from baseline at Days 14 and 28 between AlphaWave® L-Theanine and Placebo. |  | Day 0, day 14, day 28 | 
| The difference in change in the stress subscale as measured by the Depression Anxiety and Stress Scale (DASS)-21 from baseline at Days 14 and 28 between AlphaWave® L-Theanine and Placebo. |  | Day 0, day 14, day 28 | 
| The difference in change in the depression subscale as measured by the Depression Anxiety and Stress Scale (DASS)-21 from baseline at Days 14 and 28 between AlphaWave® L-Theanine and Placebo. |  | Day 0, day 14, day 28 | 
| The difference in change in the anxiety subscale as measured by the Depression Anxiety and Stress Scale (DASS)-21 from baseline at Days 14 and 28 between AlphaWave® L-Theanine and Placebo. |  | Day 0, day 14, day 28 | 
| The difference in change in the total score measured by the Depression Anxiety and Stress Scale (DASS)-21 from baseline at Days 14 and 28 between AlphaWave® L-Theanine and Placebo. |  | Day 0, day 14, day 28 | 
| The difference in change in sleep between AlphaWave® L-Theanine and Placebo from baseline at Days 14 and 28, as assessed by the Healthy People Sleep Quality Index (HPSQI). |  | Days 0, 14, and 28 | 
| The difference in change in sleep between AlphaWave® L-Theanine and Placebo from baseline at Days 14 and 28, as assessed by actigraphy readings. | Actigraphy readings will include data on sleep duration, sleep onset, wake time, sleep latency, sleep efficiency, sleep stages, arousal count, and sleep score (0-100). | Days 0, 14, and 28 | 
| The difference in change in cognition between AlphaWave® L-Theanine and Placebo from baseline at Days 14 and 28. | The difference in change in cognition will be assessed by the Computerized Mental Performance Assessment System (COMPASS): Stroop Test, Simple Reaction Time, and Choice Reaction Time. | Days 0, 14, and 28 | 
| The difference in change in mood between AlphaWave® L-Theanine and Placebo from baseline at Days 14 and 28. | The difference in change in mood will be assessed by the Profile of Mood States (POMS) questionnaire. | Days 0, 14, and 28 | 
| Incidence of pre-emergent and post-emergent adverse events (AE) following supplementation with AlphaWave® L-Theanine and Placebo. |  | 28 days | 
| Measurement of blood pressure (BP) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 0, day 14, day 28 | 
| Measurement of heart rate (HR) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 0, day 14, day 28 | 
| Measurement of aspartate aminotransferase (AST) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of alanine aminotransferase (ALT) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of alkaline phosphatase (ALP) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of total bilirubin following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of creatinine following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of electrolytes following supplementation with AlphaWave® L-Theanine and Placebo. | Electrolytes to be measured include sodium, potassium, and chloride. | screening, day 28 | 
| Measurement of glucose following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of estimated glomerular filtration rate (eGFR) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of white blood cell count (WBC) with differential following supplementation with AlphaWave® L-Theanine and Placebo. | WBC differentials include neutrophils, lymphocytes, monocytes, eosinophils, and basophils. | screening, day 28 | 
| Measurement of red blood cell count (RBC) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of hemoglobin following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of hematocrit following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of platelet count following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of immature granulocytes following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of nucleated red blood cells (RBC) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of mean corpuscular volume (MCV) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of mean corpuscular hemoglobin (MCH) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of mean corpuscular hemoglobin concentration (MCHC) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 
| Measurement of red blood cell distribution width (RDW) following supplementation with AlphaWave® L-Theanine and Placebo. |  | screening, day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety and efficacy, Stress