Clinical trial NCT05170113: Evaluate the Effectiveness and Safety of the Alpinia Galanga Formulation, Theacrine Formulation, and Caffeine Formulation on Fatigue, Mental Acuity, and Cognitive Health
Official title: A Pilot, Randomized, Double-blind, Placebo-controlled, Parallel Design Study to Evaluate the Effectiveness and Safety of an Alpinia Galanga Formulation, Theacrine Formulation, and Caffeine Formulation on Fatigue, Mental Acuity, and Cognitive Health Among Overall Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fatigue
Keywords: Energy
Fatigue
Tired
Sleep
Cognitive Health
Mental Acuity
Lead sponsor: Supplement Formulators, Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-27
Enrollment: 79
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The purpose of this study is to assess the effectiveness and safety of the Alpinia galanga formulation, Theacrine formulation, and Caffeine formulation on fatigue, mental acuity, and cognitive health among overall healthy participants

Detailed description: This is a 4-arm pilot, double-blind, randomized, placebo-controlled, parallel design study. A total of 80 subjects (20 per treatment arm) will be enrolled in a randomly assigned sequence to receive either the Alpinia galanga formulation, Theacrine formulation, Caffeine formulation, or placebo in individuals and admit to experiencing occasional fatigue (tiredness) and would like more energy.

Participants will need to complete assessments and questionnaires.

The primary objective is the evaluation of the change in the response to the VAS-F (Visual Analogue Scale to Evaluate Fatigue Severity) relative to baseline. The secondary objective is the evaluation of the change in the responses to the BCAT-SF (Brief Cognitive Health Assessment Short Form), LSEQ (Leeds Sleep Evaluation Questionnaires), and SF-36 Health Survey (Short Form 36) compared to baseline.

Safety and tolerability will be evaluated through the receipt of documentation and responses from the telephone contacts/ emails per protocol.

Eligibility criteria: Inclusion Criteria:

1. Ambulatory, male or female, 30-70 years of age
2. A body mass index (BMI) of 18.5 - 34.9
3. Admits to experiencing occasional fatigue (tiredness) and would like more energy
4. Has consumed no more than two cups of coffee or caffeinated beverage per day for seven or more days before Screening/baseline
5. Has personal access to and able to operate a smartphone, tablet, or computer with enough memory to accommodate additional application(s) and reliable internet service
6. Able to complete tests online with a computer
7. Able to print out and return documents by scan, email, or mail
8. Has regular daytime work hours or shifts, if employed (regular shift excludes night shift workers and those with rotating shifts)
9. Generally healthy and having no significant difficulty with digestion or absorption of food
10. Able to complete an Activity Log and Study Product Log daily
11. Has been generally weight stable for the past six months (give or take 6 lbs.)
12. Willing and able to give written informed consent
13. Clearly understands the procedures and study requirements
14. Willing and able to comply with all study procedures, as per protocol
15. Able to communicate, including reading, in English
16. Has not taken any nutritional supplements that may contain any of the components of the study products including Alpinia galanga, Theacrine or Caffeine for a minimum of 14 days before Screening/baseline

Exclusion Criteria:

1. Not having the basic skills needed to operate a smartphone, tablet, or computer
2. Unwilling to abstain from consuming more than two cups of coffee or caffeinated beverage/food per day and no caffeinated beverage/food after 10 am daily for the duration of the study
3. Having smoked any cigarette, electronic cigarette, cigar, or pipe, or used marijuana, any recreational drug or cannabidiol (CBD) in the past 30 days
4. Donated blood within the 30 days prior to Screening/baseline
5. Having participated in another study within 30 days before Screening/baseline
6. Being pregnant or planning on becoming pregnant during study participation; or breast feeding
7. History of allergy or sensitivity to any component of the study products
8. Currently taking or having taken within the 30 days prior to Screening/baseline any medication(s) or supplement(s) which may have a stimulant effect in the judgment of the Study Investigator/Sub-investigator
9. Having been diagnosed, received medical treatment, or taking medication daily for any of the following medical condition(s):

   * Chronic fatigue syndrome
   * Fibromyalgia
   * Sleep disorder, including sleep apnea
10. Presence of active or recurring clinically significant conditions as follows:

    * Diabetes mellitus or other endocrine disease
    * Eating disorder
    * Acute or chronic inflammatory disease or autoimmune disease
    * Cardiovascular disease including heart and blood vessel disease, arrhythmia, heart attack, stroke, or heart valve problem
    * Having a history of an abnormal electrocardiogram (ECG) unless permitted to proceed in the judgment of the Study Investigator/Sub-Investigator(s)
    * Gastrointestinal disease including gallbladder problems, gallstones, or biliary tract obstruction
    * Thyroid disease (unless on a stable dose of medication for 3 months before Screening/baseline and unlikely to change medication or dose during the study)
    * Hypertension (unless on a stable dose of medication for 3 months before Screening/baseline and unlikely to change medication or dose during the study)
    * Neurologic condition/disease
    * Cancer (unless skin cancer other than melanoma which has been treated \> 3 years before Screening/baseline)
    * Liver, pancreatic, and kidney disease
    * Pulmonary disease
    * Blood coagulation disorder or other hematologic disease
    * Other condition or medication use that would preclude participation in the study in the judgment of the Study Investigator/Sub-Investigator
11. Currently taking any medications or treatment for a psychiatric disorder (bipolar disorder, manic disorder, schizophrenia, apathetic \[inherited\] disorder), including antidepressant drugs, selective serotonin reuptake inhibitors (SSRIs), tricyclic and atypical antidepressants, benzodiazepines, CNS depressants, dextromethorphan, meperidine, monoamine oxidase inhibitors (MAOIs), pentazocine, phenothiazines, and tramadol. These may preclude participation in the study depending on the judgment of the Study Investigator/Sub-Investigator
12. Currently taking or having taken within the 30 days before Screening/baseline any hormone replacement therapy (including DHEA, estrogen, progesterone, or testosterone; 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). This may preclude participation in the study depending on the judgment of the Study Investigator/Sub-Investigator
13. 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
14. Currently consumes more than 7 standard alcoholic drinks per week for women and 14 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)
15. Unable or unwilling to avoid consuming grapefruit juice or fresh grapefruit, Seville oranges, and tangelos for the study period
16. History of known or suspected substance abuse (e.g., alcohol, opiates, Benzodiazepines, or amphetamines)
17. Having any other circumstance that precludes 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

Primary outcomes:
measure: VAS-F (Visual Analogue Scale to Evaluate Fatigue Severity)
timeFrame: 14 Days
Secondary outcomes:
measure: BCAT-SF (Brief Cognitive Health Assessment Short Form)
timeFrame: 14 Days
Other outcomes:
measure: LSEQ (Leeds Sleep Evaluation Questionnaires)
timeFrame: 14 Days
measure: SF-36 Health Survey (Short Form 36)
timeFrame: 14 Days
Locations:
city: Fort Lauderdale
country: United States
facility: Life Extension Clinical Research
state: Florida
Study officials:
affiliation: Life Extension
name: Andrew Swick, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alajmi MF, Mothana RA, Al-Rehaily AJ, Khaled JM. Antimycobacterial Activity and Safety Profile Assessment of Alpinia galanga and Tinospora cordifolia. Evid Based Complement Alternat Med. 2018 Jul 8;2018:2934583. doi: 10.1155/2018/2934583. eCollection 2018.
citation: Alpinia. (2019, October 7). Natural medicines (database on the Internet). Somerville, MA: Therapeutic Research Center. Retrieved from https://naturalmedicines.therapeuticresearch.com/databases/food,-herbssupplements/professional.aspx?productid=276
citation: Bello ML, Walker AJ, McFadden BA, Sanders DJ, Arent SM. The effects of TeaCrine(R) and caffeine on endurance and cognitive performance during a simulated match in high-level soccer players. J Int Soc Sports Nutr. 2019 Apr 18;16(1):20. doi: 10.1186/s12970-019-0287-6.
citation: Brice CF, Smith AP. Effects of caffeine on mood and performance: a study of realistic consumption. Psychopharmacology (Berl). 2002 Nov;164(2):188-92. doi: 10.1007/s00213-002-1175-2. Epub 2002 Sep 4.
citation: Caffeine. (2020, January 6). Natural Medicines (database on the Internet). Somerville, MA: Therapeutic Research Center. Retrieved from https://naturalmedicines.therapeuticresearch.com/references.aspx?productid=979
citation: Carman AJ, Dacks PA, Lane RF, Shineman DW, Fillit HM. Current evidence for the use of coffee and caffeine to prevent age-related cognitive decline and Alzheimer's disease. J Nutr Health Aging. 2014 Apr;18(4):383-92. doi: 10.1007/s12603-014-0021-7.
citation: Chudiwal, A., Jain, D., & Somani, R. (2010). Alpinia galanga Willd.-An overview on phytopharmacological properties. Indian Journal of Natural Products and Resources, 1(2), 143-149.
citation: Clewell A, Hirka G, Glavits R, Palmer PA, Endres JR, Murbach TS, Marx T, Pasics Szakonyine I. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine. J Toxicol. 2016;2016:6206859. doi: 10.1155/2016/6206859. Epub 2016 Aug 22.
citation: Dallal, G. (2017, July 10). www.Randomization.com. Retrieved from Randomization.com: http://www.randomization.com
citation: Fredholm BB, Battig K, Holmen J, Nehlig A, Zvartau EE. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 1999 Mar;51(1):83-133. No abstract available.
citation: Ghosh S, Rangan L. Alpinia: the gold mine of future therapeutics. 3 Biotech. 2013 Jun;3(3):173-185. doi: 10.1007/s13205-012-0089-x. Epub 2012 Sep 18.
citation: Haller CA, Jacob P 3rd, Benowitz NL. Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use. Clin Pharmacol Ther. 2002 Jun;71(6):421-32. doi: 10.1067/mcp.2002.124523.
citation: Haskell CF, Kennedy DO, Wesnes KA, Scholey AB. Cognitive and mood improvements of caffeine in habitual consumers and habitual non-consumers of caffeine. Psychopharmacology (Berl). 2005 Jun;179(4):813-25. doi: 10.1007/s00213-004-2104-3. Epub 2005 Jan 28.
citation: Taylor L, Mumford P, Roberts M, Hayward S, Mullins J, Urbina S, Wilborn C. Safety of TeaCrine(R), a non-habituating, naturally-occurring purine alkaloid over eight weeks of continuous use. J Int Soc Sports Nutr. 2016 Jan 13;13:2. doi: 10.1186/s12970-016-0113-3. eCollection 2016.
citation: He H, Ma D, Crone LB, Butawan M, Meibohm B, Bloomer RJ, Yates CR. Assessment of the Drug-Drug Interaction Potential Between Theacrine and Caffeine in Humans. J Caffeine Res. 2017 Sep 1;7(3):95-102. doi: 10.1089/jcr.2017.0006.
citation: Kamimori GH, McLellan TM, Tate CM, Voss DM, Niro P, Lieberman HR. Caffeine improves reaction time, vigilance and logical reasoning during extended periods with restricted opportunities for sleep. Psychopharmacology (Berl). 2015 Jun;232(12):2031-42. doi: 10.1007/s00213-014-3834-5. Epub 2014 Dec 21.
citation: Kuhman DJ, Joyner KJ, Bloomer RJ. Cognitive Performance and Mood Following Ingestion of a Theacrine-Containing Dietary Supplement, Caffeine, or Placebo by Young Men and Women. Nutrients. 2015 Nov 19;7(11):9618-32. doi: 10.3390/nu7115484.
citation: McLellan TM, Caldwell JA, Lieberman HR. A review of caffeine's effects on cognitive, physical and occupational performance. Neurosci Biobehav Rev. 2016 Dec;71:294-312. doi: 10.1016/j.neubiorev.2016.09.001. Epub 2016 Sep 6.
citation: Institute of Medicine (US) Committee on Military Nutrition Research. Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. Washington (DC): National Academies Press (US); 2001. Available from http://www.ncbi.nlm.nih.gov/books/NBK223802/
citation: Meredith SE, Juliano LM, Hughes JR, Griffiths RR. Caffeine Use Disorder: A Comprehensive Review and Research Agenda. J Caffeine Res. 2013 Sep;3(3):114-130. doi: 10.1089/jcr.2013.0016.
citation: Nehlig A. Is caffeine a cognitive enhancer? J Alzheimers Dis. 2010;20 Suppl 1:S85-94. doi: 10.3233/JAD-2010-091315.
citation: Office of New Drugs. (2005). Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. 1-37. Office of the Federal Register , National Archives and Record Administration.
citation: Qureshi S, Shah AH, Ageel AM. Toxicity studies on Alpinia galanga and Curcuma longa. Planta Med. 1992 Apr;58(2):124-7. doi: 10.1055/s-2006-961412.
citation: Rosner, B. (n.d.). Hypothesis Testing: Two-Sample Inference-Estimation of Sample Size and Power for Comparing Two Means. In B. Rosner, Fundamentals of Biostatistics. Cengage Learning. Retrieved from www.stat.buc.ca: https://www.stat.ubc.ca/~rollin/stats/ssize/n2.html
citation: Saha S, Banerjee S. Central nervous system stimulant actions of Alpinia galanga (L.) rhizome: a preliminary study. Indian J Exp Biol. 2013 Oct;51(10):828-32.
citation: Sebastiao AM, Ribeiro JA. Tuning and fine-tuning of synapses with adenosine. Curr Neuropharmacol. 2009 Sep;7(3):180-94. doi: 10.2174/157015909789152128.
citation: Hanish Singh JC, Alagarsamy V, Diwan PV, Sathesh Kumar S, Nisha JC, Narsimha Reddy Y. Neuroprotective effect of Alpinia galanga (L.) fractions on Abeta(25-35) induced amnesia in mice. J Ethnopharmacol. 2011 Oct 31;138(1):85-91. doi: 10.1016/j.jep.2011.08.048. Epub 2011 Sep 1.
citation: Sivanandan, S., & Pimple, S. (2018). Molecular Docking Studies of Alpinia galanga Phytoconstituents for Psychostimulant Activity. Advances in Biological Chemistry, 8(4),69-80
citation: Srivastava S, Mennemeier M, Pimple S. Effect of Alpinia galanga on Mental Alertness and Sustained Attention With or Without Caffeine: A Randomized Placebo-Controlled Study. J Am Coll Nutr. 2017 Nov-Dec;36(8):631-639. doi: 10.1080/07315724.2017.1342576. Epub 2017 Sep 14.
citation: Srivastava, S., & Pimple, S. (2017). Effects of Cymbopogon Flexuosus, Alpinia Galanga, and Glycyrrhiza Glabra on attention: A randomized double-blind, placebo-controlled pilot study. BAOJ Nutrition, 3, 042.
citation: van Gelder BM, Buijsse B, Tijhuis M, Kalmijn S, Giampaoli S, Nissinen A, Kromhout D. Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE Study. Eur J Clin Nutr. 2007 Feb;61(2):226-32. doi: 10.1038/sj.ejcn.1602495. Epub 2006 Aug 16.
citation: Wang Y, Yang X, Zheng X, Li J, Ye C, Song X. Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities. Fitoterapia. 2010 Sep;81(6):627-31. doi: 10.1016/j.fitote.2010.03.008. Epub 2010 Mar 20.
citation: Warburton DM. Effects of caffeine on cognition and mood without caffeine abstinence. Psychopharmacology (Berl). 1995 May;119(1):66-70. doi: 10.1007/BF02246055.
citation: Wedick NM, Brennan AM, Sun Q, Hu FB, Mantzoros CS, van Dam RM. Effects of caffeinated and decaffeinated coffee on biological risk factors for type 2 diabetes: a randomized controlled trial. Nutr J. 2011 Sep 13;10:93. doi: 10.1186/1475-2891-10-93.
citation: Zampelas A, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanadis C. Associations between coffee consumption and inflammatory markers in healthy persons: the ATTICA study. Am J Clin Nutr. 2004 Oct;80(4):862-7. doi: 10.1093/ajcn/80.4.862.
citation: Ziegenfuss TN, Habowski SM, Sandrock JE, Kedia AW, Kerksick CM, Lopez HL. A Two-Part Approach to Examine the Effects of Theacrine (TeaCrine(R)) Supplementation on Oxygen Consumption, Hemodynamic Responses, and Subjective Measures of Cognitive and Psychometric Parameters. J Diet Suppl. 2017 Jan 2;14(1):9-24. doi: 10.1080/19390211.2016.1178678. Epub 2016 May 10.
citation: Zwyghuizen-Doorenbos A, Roehrs TA, Lipschutz L, Timms V, Roth T. Effects of caffeine on alertness. Psychopharmacology (Berl). 1990;100(1):36-9. doi: 10.1007/BF02245786.