"WakeUp" for Vigilance Following Lunch
Condition: Fatigue
MeSH terms: Fatigue
Study type: Interventional

Summary: 
      This is a single center, double-blind, placebo and active controlled clinical trial comprised
      of a single drink of WakeUp beverage (in 3 doses) compared to Caffeine (100mg) and placebo
      given to health volunteers.

      Participants will be randomized regarding the order of the various beverages. Healthy
      volunteers or stable (under treatment) patients with chronic diseases) will be included. They
      will be studied 5 times, in a 2-14 days period, each time during noontime (between 11:30 and
      15:00).

      Each day of the study, the participants will follow the following schedule:

      Lunch any time between 11:30 and 13:30 Time 0: Immediately after lunch a baseline set of
      assessment. Time 30min: Participants will then consume a beverage (which will be either
      placebo or 100mg caffeine or single/double/triple dose of WakeUp in the various days) Time
      60min: Repeat the same set of assessments as done 30min after beverage Time 150min: Repeat
      the same set of assessments 2 hours after beverage Time 180min: End of day assessment
    

Detailed description: 
      This is a randomized, double-blind, controlled study with placebo and active control, to test
      the efficacy and safety of WakeUp on alertness and function in 30 healthy or chronically ill
      but stable adult volunteers.

      Participants and recruitment Thirty volunteers will be recruited via advertisements (in the
      hospital and university environment). Initial assessment of inclusion and exclusion criteria
      will take place on the primary visit, and once participants have met the criteria for
      participation and sign an informed consent, they will enter the study and undergo
      randomization. It is permitted for participants to have any chronic disease (such as
      hypertension or diabetes) if they are stable and controlled. Participants will continue
      taking their own medications (as long as they are not stimulants or sedating, in which case
      the subject will be excluded).

      Study procedure and schedule This is a single center, double-blind, placebo and active
      controlled clinical trial comprised of a single drink of WakeUp® beverage (in 3 doses)
      compared to caffeine (100mg) and placebo given to health volunteers. Participants will be
      randomized regarding the order of the various beverages.

      The following visits and schedule will comprise the study:

        1. Screening visit: In this visit study procedures will be expained, inclusionqexclusion
           criteria determined, informed consent signed).

        2. Visit 1: Participants eats their regular lunce following which a first set of studies
           takes place (see below). Immediately thereafter the participant drinks the tested
           beverage (marked A, B, C, D, E or F, randomized order regarding which beverage of the 6
           is drank at each specific study day, blinded to the participant and the staff). Thirty
           minutes after drinking a second set of studies will take place (exactly equal to the
           previous set of studies). A third set of studies (exactly the same as the previous two)
           will take place 2 hours following the drink.

        3. Visits 2, 3, 4, and 5 are exactly like visit 1, just that the beverage is one of the
           others (randomized), such that each participants after completing 5 visits had all
           tested beverages: placebo, 100mg Caffeine, WakeUp® regular dose, WakeUp® double dose,
           WakeUp® triple dose.

        4. Visit 7: A telephone call or a face-to-face visit (based on the preference of the
           participants) one week after the study to make sure there are no side effects and to
           close participation.

      The time between screening and visit 1 can be any time between 0 (screening and visit 1 on
      the same day) to 1 month.

      The time between any two other visits (visit 1 to 2, 2 to 3 etc) can be any time between 1 to
      14 days.

      Each one of visits 1 to 5 will begin after lunch, between 11:30 and 15:00, preferable at the
      same time in all visits 1 to 5.

      Randomization Treatment will be randomized for the order of beverage tested (A to E) in
      visits 1 to 5 by a computer-generated randomization scheme (randome function written in
      JAVA). At the beginning of visit 1 randomization will be performed for the whole study period
      (i.e. for which of beverages A,B,C,D,E to be drunk on which of the visits 1,2,3,4,5).

      Blinding Blinding will be kept by the manufacturer of the beverages (Frutarom USA, Inc). All
      5 beverages (placebo, 100mg Caffeine, WakeUp® regular dose, WakeUp® double dose, and WakeUp®
      triple dose) will be marked by a letter beween A to E, which will be blinded to the
      participants and the staff of the study. Only after the completion of the study (all 30
      participants), and statistical analysis and reporting will the various beverages (letters)
      will be unblinded. The only occasion of unblinding prior to study completion will be the
      unexpected occasion of a serious side effect.

      Set of testing for the study

      At all testing times (3 times at every visit from visit 1 to 5, each time point after lunch,
      30min after beverage, 2h after beverage) the following tests will be performed:

      Vital signs (blood pressure and pulse rate) Asking about side effects Visual Analog Scale for
      Alertness (see above) Immediate word recall test (see above) Neurocognitive function testing
      by Cambridge Cognition on an ipad tablet.

      The following neurocognitive function tests will be performed:

      Attention:

      RTI- Reaction Time - 2-3 minutes

      The participant must select and hold a button at the bottom of the screen. Circles are
      presented above (one for the simple mode, and five for the five-choice mode.) In each case, a
      yellow dot will appear in one of the circles, and the participant must react as soon as
      possible, releasing the button at the bottom of the screen, and selecting the circle in which
      the dot appeared. Outcome measures are divided into reaction time and movement time for both
      the simple and five-choice variants.

      RVP - Rapid Visual Information Processing - 7 minutes

      A white box is shown in the centre of the screen, inside which digits from 2 to 9 appear in a
      pseudo-random order, at the rate of 100 digits per minute. Participants are requested to
      detect target sequences of digits (for example, 2-4-6, 3-5-7, 4-6-8). When the participant
      sees the target sequence they must respond by selecting the button in the centre of the
      screen as quickly as possible. The level of difficulty varies with either one- or
      three-target sequences that the participant must watch for at the same time. Outcome measures
      cover latency (speed of response), probability of false alarms and sensitivity.

      Executive Function:

      MTT- Multitasking Test- 8 minutes

      The test displays an arrow which can appear on either side of the screen (right or left) and
      can point in either direction (to the right or to the left). Each trial displays a cue at the
      top of the screen that indicates to the participant whether they have to select the right or
      left button according to the "side on which the arrow appeared" or the "direction in which
      the arrow was pointing". In some sections of the task this rule is consistent across trials
      (single task) while in others it may change from trial to trial in a randomised order
      (multitasking). Using both rules in a flexible manner places a higher demand on cognition
      than using a single rule.

      Some trials display congruent stimuli (e.g. arrow on the right side pointing to the right)
      whereas other trials display incongruent stimuli, which require a higher cognitive demand
      (e.g. arrow on the right side of the screen pointing to the left). Outcome measures for the
      Multitasking Test include response latencies and error scores that reflect the participant's
      ability to manage multitasking and the interference of incongruent task-irrelevant
      information on task performance (i.e. a Stroop-like effect).

      SSP- Spacial Span - 5 minutes

      White squares are shown on the screen, some of which briefly change colour in a variable
      sequence. The participant must then select the boxes which changed colour in the same order
      that they were displayed by the computer (for the forward variant) or in the reverse order
      (for backward variant). The number of boxes in the sequence increases from two at the start
      of the test, to nine at the end and the sequence and colour are varied through the test.
      Outcome measures cover span length (the longest sequence successfully recalled), errors,
      number of attempts and latency (speed of response).

      Memory:

      SWM-Spatial Working Memory - 4 minutes

      The test begins with a number of coloured squares (boxes) shown on the screen. The aim of
      this test is that by selecting the boxes and using a process of elimination, the participant
      should find one yellow 'token' in each of a number of boxes and use them to fill up an empty
      column on the right-hand side of the screen. Depending on the difficulty level used for this
      test, the number of boxes can be gradually increased until a maximum of 12 boxes are shown
      for the participants to search. The colour and position of the boxes used are changed from
      trial to trial to discourage the use of stereotyped search strategies. Outcome measures
      include errors (selecting boxes that have already been found to be empty and revisiting boxes
      which have already been found to contain a token) and strategy and latency.

      The data for vital signs, potential side effects, alertness and iWRT will be kept in a local
      case report form. The data of the Cambridge Cognition tests are stored in the tablet, or sent
      to the cloud if the tablet is connected to wifi at that time. All data are sent to the cloud
      whenever the tablet connects to wifi. The data are compiled by Cambridge and the raw data are
      put into a CSV file which can be downloaded from the tablet directly and can open in
      Microsoft Excel. The secure private cloud environment is provided by HIPAA-accredited
      supplier Armor. The data are secured via military grade encryption (256-bit key file
      encryption) and are only accessible to authorized users. As an additional security measure,
      Cambridge Cognition commissions an independent security check on the system each year and
      Cambridge Cognition and the CANTAB Connect platform have been audited by the Medicines and
      Healthcare products Regulatory Agency and British Standards Institute, as well as external
      audits arranged by customers.
    

Intervention name(s): "Wake Up"; Caffeine
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): The current composition of the WakeUp® beverage consists of herbal extracts of guarana, green tea, elderberry and Fruit-up; Caffeine
Other intervention name(s): Caffeine, Placebo
Intervention MeSH terms: Caffeine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Participants will be randomized regarding the order of the various beverages they drink, in a double blind placebo and active control model.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention