Effects of Microencapsulated Sublingual Glycine (Bidicin) on Cognitive Performance in Healthy Men After an Acute Stressor

Overview

The aim of this study is to assess whether intake of Glycine (MSG) leads to an increase of cognitive performance after an acute stressor compared to placebo. One group will receive verum, one group placebo and one group will not receive any intervention. Cognitive testing will be performed in connection with the Trier Social Stress Test (TSST).

Full Title of Study: “Effects of Microencapsulated Sublingual Glycine (Bidicin) on Cognitive Performance in Healthy Men After an Acute Stressor – a Randomized, Partly Double-blind Placebo-controlled Clinical Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: March 15, 2018

Detailed Description

Stress can enhance or impair memory performances depending on the timing of the stressor and the timing of the memory processes in relation to the stressor. If stress occurs directly before or during the retrieval of information, the performance is impaired. Decreased performances using an acute stressor were also observed for other domains of cognitive functioning like working memory, interference control, cognitive flexibility and attention tasks.

Glycine, the simplest of the amino acids, is an essential component of important biological molecules, a key substance in many metabolic reactions, the major inhibitory neurotransmitter in the spinal cord and brain stem, and an anti-inflammatory, cytoprotective, and immune modulating substance. Studies have found positive effects of Glycine on episodic memory retrieval and in a word retrieval task.

To assess the effect of Glycine (MSG) on cognitive performance after an acute stressor, subjects perform baseline cognitive testing before intake of investigational products (Glycine (MSG), placebo or nothing) and participation in a stress test (Trier Social Stress Test – TSST). After the TSST stress-induced changes in cognitive performance are assessed. A second treatment intake takes place between the first and the remaining cognitive tests.

Interventions

  • Dietary Supplement: Microencapsulated Sublingual Glycine (MSG)
    • Glycine (MSG) tablet
  • Dietary Supplement: Placebo
    • Lactose tablet manufactured to mimic Glycine (MSG) tablet

Arms, Groups and Cohorts

  • Active Comparator: Glycine (MSG)
    • Microencapsulated Sublingual Glycine (MSG): 1 tablet prior to TSST; 1 tablet after the TSST
  • Placebo Comparator: Placebo
    • Lactose: 1 tablet prior to TSST; 1 tablet after the TSST
  • No Intervention: No treatment

Clinical Trial Outcome Measures

Primary Measures

  • Delayed memory performance after the TSST (correct words)
    • Time Frame: 20 minutes after second product intake
    • Efficacy of the intake of Glycine (MSG) on performance in the Verbal Learning and Memory Test (VLMT) delayed recall task (number of correct words) compared to placebo and control group

Secondary Measures

  • Delayed memory performance before and during the TSST
    • Time Frame: 15 minutes before and 42 minutes after first product intake
    • Efficacy of the intake of Glycine (MSG) on performance in the Verbal Learning and Memory Test (VLMT) delayed recall task (number of correct words, number of perseverations and wrong words) compared to placebo and control group
  • Immediate memory performance before and after the TSST
    • Time Frame: 44 minutes before, 13 and 48 minutes after first product intake
    • Efficacy of the intake of Glycine (MSG) on Performance in the Verbal Learning and Memory Test (VLMT) immediate recall task (number of correct words, decreased number of perseverations and wrong words) compared to placebo and control group
  • VAS stress
    • Time Frame: 20 minutes, 37 minutes and 46 minutes after first product intake
    • Efficacy of the intake of Glycine (MSG) on subjective evaluation of acute stress compared to placebo and control group measured on a Visual Analogue Scale (VAS). The VAS is a 10cm bipolar visual scale ranging from “not at all” to “highly”. VAS scores are obtained by using a ruler and measuring the position of the participant’s mark with millimeter precision. To control for possible variations due to printing, the total length of the line is also measured and percentage scores for each subject are computed. Percentage scores range from 0-100.
  • VAS anxiety
    • Time Frame: 20 minutes, 37 minutes and 46 minutes after first product intake
    • Efficacy of the intake of Glycine (MSG) on subjective evaluation of acute anxiety compared to placebo and control group measured on a Visual Analogue Scale (VAS). The VAS is a 10cm bipolar visual scale ranging from “not at all” to “highly”. VAS scores are obtained by using a ruler and measuring the position of the participant’s mark with millimeter precision. To control for possible variations due to printing, the total length of the line is also measured and percentage scores for each subject are computed. Percentage scores range from 0-100.
  • VAS insecurity
    • Time Frame: 20 minutes, 37 minutes and 46 minutes after first product intake
    • Efficacy of the intake of Glycine (MSG) on subjective evaluation of acute insecurity compared to placebo and control group measured on a Visual Analogue Scale (VAS). The VAS is a 10cm bipolar visual scale ranging from “not at all” to “highly”. VAS scores are obtained by using a ruler and measuring the position of the participant’s mark with millimeter precision. To control for possible variations due to printing, the total length of the line is also measured and percentage scores for each subject are computed. Percentage scores range from 0-100.
  • VAS sleepiness
    • Time Frame: 20 minutes, 37 minutes and 46 minutes after first product intake
    • Efficacy of the intake of Glycine (MSG) on subjective evaluation of acute sleepiness compared to placebo and control group measured on a Visual Analogue Scale (VAS). The VAS is a 10cm bipolar visual scale ranging from “not at all” to “highly”. VAS scores are obtained by using a ruler and measuring the position of the participant’s mark with millimeter precision. To control for possible variations due to printing, the total length of the line is also measured and percentage scores for each subject are computed. Percentage scores range from 0-100.
  • VAS tension
    • Time Frame: 20 minutes, 37 minutes and 46 minutes after first product intake
    • Efficacy of the intake of Glycine (MSG) on subjective evaluation of acute tension compared to placebo and control group measured on a Visual Analogue Scale (VAS). The VAS is a 10cm bipolar visual scale ranging from “not at all” to “highly”. VAS scores are obtained by using a ruler and measuring the position of the participant’s mark with millimeter precision. To control for possible variations due to printing, the total length of the line is also measured and percentage scores for each subject are computed. Percentage scores range from 0-100.
  • VAS lack of energy
    • Time Frame: 20 minutes, 37 minutes and 46 minutes after first product intake
    • Efficacy of the intake of Glycine (MSG) on subjective evaluation of acute lack of energy compared to placebo and control group measured on a Visual Analogue Scale (VAS). The VAS is a 10cm bipolar visual scale ranging from “not at all” to “highly”. VAS scores are obtained by using a ruler and measuring the position of the participant’s mark with millimeter precision. To control for possible variations due to printing, the total length of the line is also measured and percentage scores for each subject are computed. Percentage scores range from 0-100.
  • STAI-state
    • Time Frame: 20 minutes and 46 minutes after first product intake
    • Efficacy of the intake of Glycine (MSG) on state anxiety as measured by the State Trait Anxiety Inventory (STAI) compared to placebo and control group. The STAI-state measures anxiety as a temporary emotional state and comprises 20 items. Answers are given on a four-point rating scale ranging from 1 = “not at all” to 4 = “very true”. Some STAI questions relate to the absence of anxiety, and are reversely scored. For analysis of the STAI-scale, items are combined in one scale, which then informs about state anxiety. The score range is 20-80; higher scores indicate more anxiety.
  • Systolic and diastolic blood pressure
    • Time Frame: 25 minutes and 46 minutes after first product intake
    • Efficacy of the intake of Glycine (MSG) on blood pressure in response to the TSST compared to placebo and control group
  • Delayed memory performance after the TSST (perseverations, wrong words)
    • Time Frame: 20 minutes after second product intake
    • Efficacy of the intake of Glycine (MSG) on performance in the Verbal Learning and Memory Test (VLMT) delayed recall task (decreased number of perseverations and wrong words) compared to placebo and control group
  • Cognitive performance before and after the TSST (Stroop)
    • Time Frame: 10 minutes before first product intake and 23 minutes after second product intake
    • Efficacy of the intake of Glycine (MSG) on performance in the Stroop test (speed and accuracy) compared to placebo and control group
  • Cognitive performance before and after the TSST (CogTrack)
    • Time Frame: 40 minutes before first product intake, immediately after second product intake
    • Efficacy of the intake of Glycine (MSG) on performance in attention, working memory, learning and recognition tasks of CogTrack compared to placebo and control group
  • Heart rate
    • Time Frame: Continous measurement starting 10 minutes after first product intake and ending 10 minutes after second product intake
    • Efficacy of the intake of Glycine (MSG) on heart rate in response to the TSST compared to placebo and control group
  • Salivary Cortisol
    • Time Frame: 45, 10 minutes before first product intake, 28, 46, 55 minutes after first product intake, 10, 20, 35 and 50 minutes after second product intake
    • Efficacy of the intake of Glycine (MSG) on salivary cortisol raw values in response to the TSST compared to placebo and control group

Participating in This Clinical Trial

Inclusion Criteria

  • subject signs the informed consent to participate in the study
  • normally stressed subjects as verified by the TICS questionnaire with scores >3 and <37

Exclusion Criteria

  • smoker
  • any known allergies to the test substances
  • lactose intolerance
  • any known addiction to drugs and/or alcohol
  • hyper- or hypotension (except for those whose blood pressure is stable using medication for more than 3 months)
  • known hyper- or hypothyroidism unless treated and under control (stable for more than 3 months)
  • any known current/acute or chronic physical or psychological diseases besides minor medical conditions (e.g. seasonal allergies)
  • intake of any medication which may affect the cognitive performance (e.g. psychotropics, sedating or stimulating medication)
  • any color vision impairment (e.g. red-green deficiency)
  • intake of dietary supplements or homoeopathic remedies during 2 weeks before V1 or during the study conduction
  • consumption of alcohol during 2 days before V1 or during the study conduction
  • excessive caffeine consumption (>400 mg caffeine/day or >= 4 cups of caffeinated coffee)
  • on a strict diet or practicing sport, extensively
  • attending an exam one week before and after the study participation
  • subjects having previously participated in the TSST
  • employee of the sponsor or Contract Research Organisation (CRO)
  • Investigator doubts truthfulness of self-reported health information
  • not suitable because of limited verbal and cognitive abilities

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: 40 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Daacro
  • Collaborator
    • OOO MNPK BIOTIKI
  • Provider of Information About this Clinical Study
    • Principal Investigator: Juliane Hellhammer, PhD – Daacro

References

Schwabe L, Wolf OT. Stress and multiple memory systems: from 'thinking' to 'doing'. Trends Cogn Sci. 2013 Feb;17(2):60-8. doi: 10.1016/j.tics.2012.12.001. Epub 2013 Jan 2. Review.

Shields GS, Sazma MA, McCullough AM, Yonelinas AP. The effects of acute stress on episodic memory: A meta-analysis and integrative review. Psychol Bull. 2017 Jun;143(6):636-675. doi: 10.1037/bul0000100. Epub 2017 Apr 3. Review.

Shields GS, Sazma MA, Yonelinas AP. The effects of acute stress on core executive functions: A meta-analysis and comparison with cortisol. Neurosci Biobehav Rev. 2016 Sep;68:651-668. doi: 10.1016/j.neubiorev.2016.06.038. Epub 2016 Jun 28. Review.

Lupien SJ, Gillin CJ, Hauger RL. Working memory is more sensitive than declarative memory to the acute effects of corticosteroids: a dose-response study in humans. Behav Neurosci. 1999 Jun;113(3):420-30.

Olver JS, Pinney M, Maruff P, Norman TR. Impairments of spatial working memory and attention following acute psychosocial stress. Stress Health. 2015 Apr;31(2):115-23. doi: 10.1002/smi.2533. Epub 2014 Jan 3.

Schoofs D, Preuss D, Wolf OT. Psychosocial stress induces working memory impairments in an n-back paradigm. Psychoneuroendocrinology. 2008 Jun;33(5):643-53. doi: 10.1016/j.psyneuen.2008.02.004. Epub 2008 Mar 21.

Shields GS, Trainor BC, Lam JC, Yonelinas AP. Acute stress impairs cognitive flexibility in men, not women. Stress. 2016 Sep;19(5):542-6. doi: 10.1080/10253890.2016.1192603. Epub 2016 Jun 20.

Gundersen RY, Vaagenes P, Breivik T, Fonnum F, Opstad PK. Glycine–an important neurotransmitter and cytoprotective agent. Acta Anaesthesiol Scand. 2005 Sep;49(8):1108-16. Review.

File SE, Fluck E, Fernandes C. Beneficial effects of glycine (bioglycin) on memory and attention in young and middle-aged adults. J Clin Psychopharmacol. 1999 Dec;19(6):506-12.

Schwartz BL, Hashtroudi S, Herting RL, Handerson H, Deutsch SI. Glycine prodrug facilitates memory retrieval in humans. Neurology. 1991 Sep;41(9):1341-3.

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