Effects of a Theanine for Stress Relief Formulation in Individuals Who Report Occasional Moderate High Levels of Stress.

Stress Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effects of a Theanine for Stress Relief Formulation on Stress, Burnout Component, Mood, and Sleep in Individuals Who Report Occasional Moderate or High Levels of Stress

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05854017
• Other study ID #: Protocol CL114
• Status: Recruiting
• Phase: N/A
• Start date: February 9, 2023
• Est. completion date: July 20, 2024

Study information

• Verified date: January 2024
• Source: Supplement Formulators, Inc.
• Contact: Dr. Steven Hirsh
• Phone: 866-517-4536
• Email: shirsh[@]lifeextension.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the effectiveness and safety of the theanine for stress relief formulation versus placebo on stress, burnout component, mood and sleep

Description:

This is a double-blind, randomized, placebo-controlled study to evaluate the effects of a theanine for stress relief formulation on stress, burnout component, mood, and sleep in individuals who report occasional moderate or high levels of stress.

Participants will be asked to completed assessments and questionnaires as well as obtain a self saliva sample.

The primary objective is to evaluate the median change in response to the theanine formulation on stress from completed questionnaires, Perceived Stress Scale-14 (PSS-14) and the State Trait Anxiety Inventory (STAI) for stress.

The secondary objective is to evaluate the median change in response to the theanine formulation on stress from completed questionnaires, Depression, Anxiety and Stress Scale (DASS-21), Leeds Sleep Evaluation Questionnaires (LSEQ), Maslach Burnout Inventory General Survey (MBI-GS) and Short Form 36 Health Survey and Cortisol levels.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: July 20, 2024
• Est. primary completion date: June 20, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Ambulatory, male or female, 21-65 years of age

2. A BMI of 18.5-34.9

3. Admits to having occasional periods of moderate or severe stress on the screening questionnaire

4. Indicating a PSS-14 score > 19 (identification as having moderate or high perceived stress)

5. Have personal access to and able to operate a smartphone, tablet, or computer with enough memory to accommodate additional application(s) and have a reliable internet service

6. Able to take a saliva specimen and store it immediately in a freezer before breakfast at three different times during the study

7. Generally healthy and having no difficulty swallowing a tablet

8. Employed in a work setting, at-home or in a caregiver role and has regular daytime work hours or shifts, if employed (regular shift excludes night shift workers and those with rotating shifts) with no anticipated changes in the schedule, if enrolled

9. Has been generally weight stable for the past six months (+/- 6 lbs.)

10. Willing and able to give written informed consent

11. Clearly understand and are willing to comply with the study procedures and requirements

12. Willing and able to comply with all study procedures, including following recommendations to maintain their usual diet and regular activity, as per protocol

13. Able to communicate and read in the English language

14. Are not currently taking any supplements or foods containing L-theanine or D-theanine within 30 days before Screening and will not for the duration of the study

Exclusion Criteria:

1. Not having the basic skills needed to operate a smartphone, tablet, or computer

2. Having smoked any cigarette, electronic cigarette, cigar, pipe, or used a recreational drug as well as any product containing cannabidiol (CBD) or tetrahydrocannabinol (THC) in the past 30 days prior to Screening

3. Having donated blood within 30 days before Screening

4. Having been diagnosed with dysphagia or difficulty swallowing

5. Having participated in another study within 30 days prior to Screening

6. Being pregnant, planning on becoming pregnant during study participation or refusing to indicate willingness to use a medically acceptable form of birth control, if applicable, during study participation, or breast feeding

7. Are participating in a stress management program and will not for the duration of the study participation

8. Unable to avoid any form of intense exercise or a significant change in exercise routine during the day of saliva specimen collection

9. Currently taking any supplements containing L-theanine or D-theanine within the past 30 days before Screening

10. Currently taking supplements including melatonin, 5-hydroxytryptophan, Calamus, California poppy, St. John's wort, S-adenosylmethionine (SAM-E), catnip, hops, kava, valerian, Jamaican dogwood, skullcap, yerba mansa, Hawaiian baby woodrose, L-theanine, magnesium, or any other supplement for stress, burnout, mood, or sleep. These may preclude participation in the study dependent the judgment of the Study Investigator/Sub-Investigator

11. Having been diagnosed, received medical treatment, taking medications or supplements daily for the following medical condition(s):

• Stress disorder (including post-traumatic stress disorder (PTSD)

• Sleep disorder (including insomnia diagnosed by a physician)

• Psychiatric disorder. These may preclude participation in the study dependent on the judgment of the Study Investigator/Sub-Investigator.

• Acute or chronic inflammatory or autoimmune disease

• Active infection

• Active periodontal disease

12. Presence of active or recurring clinically significant conditions as follows:

• Diabetes mellitus (except on a stable dose of Metformin up to 1000 mg per day only for managing the diabetes mellitus for > 3 months before Screening, unlikely to change medication or dose during the study, and under the care of a physician having seen the physician within 6 months before Screening)

• Endocrine disease (other than diabetes mellitus)

• Eating disorder

• Cardiovascular disease including heart and blood vessel disease, arrhythmia, heart attack, stroke, or heart valve problem

• Gastrointestinal disease including gallbladder problems, gallstones, or biliary tract obstruction

• Thyroid disease (except on a stable dose of medication for = 3 months before Screening and unlikely to change medication or dose during the study)

• Hypertension (except on a stable dose of medication for = 3 months before Screening and unlikely to change medication or dose during the study)

• Neurologic condition/disease

• Cancer (including skin cancer) which has been treated = 5 years before Screening or at the discretion of the Study Investigator/Sub-Investigator

• Liver, pancreatic, and kidney disease

• Pulmonary disease

• Blood coagulation disorder or other hematologic disease

• Any other condition or medication that may preclude study participation in the judgement of the Study Investigator/Sub-Investigator

13. Currently taking or having taken within the 30 days before Screening any hormone replacement therapy, except those utilized as a method of birth control and which have been taken for > 3 months with no anticipated change for the duration of the study period

14. Having had a surgical procedure or having an internal medical device which, in the judgment of the Study Investigator/Sub-Investigator, would preclude participation in the study

15. Currently consumes more than 4 standard alcoholic drinks per week for women and 7 drinks per week for men (a standard alcoholic drink is defined as one bottle/can of beer, one glass of wine, or one ounce of hard liquor)

16. Unable or unwilling to avoid consuming grapefruit juice or fresh grapefruit, Seville oranges, and tangelos for the duration of the study period

17. History of known or suspected substance abuse (e.g., alcohol, opiates, benzodiazepines, or amphetamines) 18 Having any other circumstance that may preclude study participation in the judgment of the Study Investigator/Sub-Investigator, including use of other nutritional supplements, which will be evaluated on a case-by-case basis

Related Conditions & MeSH terms

• Stress

Intervention

Dietary Supplement:
• Theanine for stress relief formulation
Theanine for stress relief formulation tablet
• Placebo
Placebo tablet

Locations

Country	Name	City	State
United States	Life Extension Clinical Research, Inc.	Fort Lauderdale	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Supplement Formulators, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (30)

Ahn RS, Lee YJ, Choi JY, Kwon HB, Chun SI. Salivary cortisol and DHEA levels in the Korean population: age-related differences, diurnal rhythm, and correlations with serum levels. Yonsei Med J. 2007 Jun 30;48(3):379-88. doi: 10.3349/ymj.2007.48.3.379. — View Citation

Borzelleca JF, Peters D, Hall W. A 13-week dietary toxicity and toxicokinetic study with l-theanine in rats. Food Chem Toxicol. 2006 Jul;44(7):1158-66. doi: 10.1016/j.fct.2006.03.014. Epub 2006 Apr 26. — View Citation

Care, I. f. Q. a. E. i. H. (2020). Depression: What is burnout? Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK279286/

Dallal, G. (2021). www.Randomization.com. Retrieved from http://www.randomization.com

Drugs, O. o. N. (2005). Guidance for Industry. Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. Retrieved from https://www.fda.gov/media/72309/download

Fernandez-Guasti A, Fiedler JL, Herrera L, Handa RJ. Sex, stress, and mood disorders: at the intersection of adrenal and gonadal hormones. Horm Metab Res. 2012 Jul;44(8):607-18. doi: 10.1055/s-0032-1312592. Epub 2012 May 11. — View Citation

Hidese S, Ogawa S, Ota M, Ishida I, Yasukawa Z, Ozeki M, Kunugi H. Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients. 2019 Oct 3;11(10):2362. doi: 10.3390/nu11102362. — View Citation

Hidese S, Ota M, Wakabayashi C, Noda T, Ozawa H, Okubo T, Kunugi H. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Acta Neuropsychiatr. 2017 Apr;29(2):72-79. doi: 10.1017/neu.2016.33. Epub 2016 Jul 11. — View Citation

Higashiyama, A., Htay, H, Ozeki, M Et Al. (2011). Effects of L-theanine on attention and reaction time response. Journal of Functional Foods, 3, 171-178.

Kakuda T, Hinoi E, Abe A, Nozawa A, Ogura M, Yoneda Y. Theanine, an ingredient of green tea, inhibits [3H]glutamine transport in neurons and astroglia in rat brain. J Neurosci Res. 2008 Jun;86(8):1846-56. doi: 10.1002/jnr.21637. — View Citation

Kim EJ, Dimsdale JE. The effect of psychosocial stress on sleep: a review of polysomnographic evidence. Behav Sleep Med. 2007;5(4):256-78. doi: 10.1080/15402000701557383. — View Citation

Kim S, Jo K, Hong KB, Han SH, Suh HJ. GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. Pharm Biol. 2019 Dec;57(1):65-73. doi: 10.1080/13880209.2018.1557698. — View Citation

Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007 Jan;74(1):39-45. doi: 10.1016/j.biopsycho.2006.06.006. Epub 2006 Aug 22. — View Citation

Levine A, Zagoory-Sharon O, Feldman R, Lewis JG, Weller A. Measuring cortisol in human psychobiological studies. Physiol Behav. 2007 Jan 30;90(1):43-53. doi: 10.1016/j.physbeh.2006.08.025. Epub 2006 Oct 19. — View Citation

Lopes Sakamoto F, Metzker Pereira Ribeiro R, Amador Bueno A, Oliveira Santos H. Psychotropic effects of L-theanine and its clinical properties: From the management of anxiety and stress to a potential use in schizophrenia. Pharmacol Res. 2019 Sep;147:104395. doi: 10.1016/j.phrs.2019.104395. Epub 2019 Aug 11. — View Citation

Miodownik C, Maayan R, Ratner Y, Lerner V, Pintov L, Mar M, Weizman A, Ritsner MS. Serum levels of brain-derived neurotrophic factor and cortisol to sulfate of dehydroepiandrosterone molar ratio associated with clinical response to L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients. Clin Neuropharmacol. 2011 Jul-Aug;34(4):155-60. doi: 10.1097/WNF.0b013e318220d8c6. — View Citation

Nathan PJ, Lu K, Gray M, Oliver C. The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006;6(2):21-30. — View Citation

Perez-Valdecantos D, Caballero-Garcia A, Del Castillo-Sanz T, Bello HJ, Roche E, Cordova A. Stress Salivary Biomarkers Variation during the Work Day in Emergencies in Healthcare Professionals. Int J Environ Res Public Health. 2021 Apr 9;18(8):3937. doi: 10.3390/ijerph18083937. — View Citation

Ritsner MS, Miodownik C, Ratner Y, Shleifer T, Mar M, Pintov L, Lerner V. L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study. J Clin Psychiatry. 2011 Jan;72(1):34-42. doi: 10.4088/JCP.09m05324gre. Epub 2010 Nov 30. — View Citation

Rogers PJ, Smith JE, Heatherley SV, Pleydell-Pearce CW. Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology (Berl). 2008 Jan;195(4):569-77. doi: 10.1007/s00213-007-0938-1. Epub 2007 Sep 23. — View Citation

Rosner, B. (2006). Hypothesis Testing Two-Sample Inference. In Fundamentals of Biostatistics (6th ed., pp. 331-334): Duxbury Press.

Sanford LD, Suchecki D, Meerlo P. Stress, arousal, and sleep. Curr Top Behav Neurosci. 2015;25:379-410. doi: 10.1007/7854_2014_314. — View Citation

Scheid L, Ellinger S, Alteheld B, Herholz H, Ellinger J, Henn T, Helfrich HP, Stehle P. Kinetics of L-theanine uptake and metabolism in healthy participants are comparable after ingestion of L-theanine via capsules and green tea. J Nutr. 2012 Dec;142(12):2091-6. doi: 10.3945/jn.112.166371. Epub 2012 Oct 24. — View Citation

Silva BKR, Quaresma FRP, Maciel EDS, Figueiredo FWDS, Sarraf JS, Adami F. Correlation Between Stress and Quality of Life Experienced by Caregivers: Perception of a Group of Healthcare Professionals. Open Nurs J. 2017 Sep 27;11:135-141. doi: 10.2174/1874434601711010135. eCollection 2017. — View Citation

Tsujita S, Morimoto K. Secretory IgA in saliva can be a useful stress marker. Environ Health Prev Med. 1999 Apr;4(1):1-8. doi: 10.1007/BF02931243. — View Citation

Unno K, Tanida N, Ishii N, Yamamoto H, Iguchi K, Hoshino M, Takeda A, Ozawa H, Ohkubo T, Juneja LR, Yamada H. Anti-stress effect of theanine on students during pharmacy practice: positive correlation among salivary alpha-amylase activity, trait anxiety and subjective stress. Pharmacol Biochem Behav. 2013 Oct;111:128-35. doi: 10.1016/j.pbb.2013.09.004. Epub 2013 Sep 16. — View Citation

Weitzman ED, Fukushima D, Nogeire C, Roffwarg H, Gallagher TF, Hellman L. Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinol Metab. 1971 Jul;33(1):14-22. doi: 10.1210/jcem-33-1-14. No abstract available. — View Citation

WHO (2019) Burn out an occupation phenomenon. International Classification of Diseases. Retrieved from https://www.who.int/news/item/28-05-2019-burn-out-an-occupational-phenomenon-international-classification-of-diseases

Williams JL, Everett JM, D'Cunha NM, Sergi D, Georgousopoulou EN, Keegan RJ, McKune AJ, Mellor DD, Anstice N, Naumovski N. The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review. Plant Foods Hum Nutr. 2020 Mar;75(1):12-23. doi: 10.1007/s11130-019-00771-5. — View Citation

Yaribeygi H, Panahi Y, Sahraei H, Johnston TP, Sahebkar A. The impact of stress on body function: A review. EXCLI J. 2017 Jul 21;16:1057-1072. doi: 10.17179/excli2017-480. eCollection 2017. — View Citation

* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Perceived Stress Scale (PSS-14)	Assessment of the mean change in the results of the Perceived Stress Scale (PSS-14) from baseline. There are 14 items and total scores range from 0-56. The lower the score indicates a lower level of stress.	28 days
Primary	State-Trait Anxiety Inventory (STAI)	Assessment of the mean change in the results of the State-Trait Anxiety Inventory (STAI) from baseline. This is a 20-item questionnaire which includes separate measures of state and trait anxiety. The total scores range from 0-63. The lower the score indicates a better outcome.	28 days
Secondary	Depression, Anxiety and Stress Scale-21 (DASS-21)	Assessment of the mean change in the results of Depression, Anxiety and Stress Scale-21 (DASS-21) from baseline. There are 21 items consisting of three scales (Depression, Anxiety and Stress) contains 7 items and scores from each scale can range from 0-56. The lower the scores for each scale indicates a better outcome.	28 days
Secondary	Leeds Sleep Evaluation Questionnaire (LSEQ)	Assessment of the mean change in the results of the Leeds Sleep Evaluation Questionnaires (LSEQ) from baseline. This questionnaire consists of ten self-rating questions related to four consecutive aspects of sleep (getting to sleep, quality of sleep, awakening from sleep and behavior following sleep). The total LSEQ score can range from 0-100. The higher the total global LSEQ score indicates a better outcome.	28 days
Secondary	Maslach Burnout Inventory (MBI-GS)	Assessment of the mean change in the results of Maslach Burnout Inventory (MBI-GS) from baseline. This survey consists of 16 statements of job-related feelings. It consists of 3 subscales including Emotional Exhaustion, Depersonalization and Professional Accomplishment. The total score can range from 0 to 96. The lower the score for the Emotional Exhaustion and Depersonalization components represent a better outcome and a higher score for the Professional Accomplishment represents a better outcome.	28 days
Secondary	Short Form -36 Health Survey (SF-36)	Assessment of the mean change in the results of the Short Form-36 Health Survey (SF-36) from baseline. This is a 36-item questionnaire that covers eight domains including physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue and general health perceptions. The scores from each domain can range from 0 to 100. The higher the scores for each domain indicates a better outcome.	28 days
Secondary	Cortisol Levels	Assessment of the mean change in the results of Cortisol levels from baseline	28 days