The Effect of AMP Human Sodium Bicarbonate Lotion on Dehydrated Heat Stress
Condition: Fluid Retention; Sodium Retention; Heat Stress; Dehydration (Physiology); Renal Injury; Electrolyte and Fluid Balance Conditions
MeSH terms: Dehydration; Hypernatremia; Heat Stress Disorders
Study type: Interventional

Summary: 
      The primary purpose of the proposed study is to evaluate the effects of a topical sodium
      bicarbonate lotion (PR Lotion, AMP Human, Park City, UT) on measures of hydration status and
      fluid balance in humans when exposed to the heat while resting and during light/moderate
      aerobic exercise. A secondary purpose is to examine these same effects with two differing
      dosage patterns of the lotion. A tertiary purpose is to investigate the effect of an amino
      acid rehydration beverage in comparison to a placebo on measurements of hydration, subjective
      assessments of stress, and vestibular as well as musculoskeletal measures of fatigue for up
      to 24-hours after the completion of both passive and exertional heat stress within a
      dehydrated state.
    

Detailed description: 
      Design This laboratory study will involve the inclusion of 20 male participants from the
      local community and university who are within the age range of 18 - 45 years old and can be
      classified as recreationally active adults as indicated by a VO2max minimum (45 ml/kg/min)
      who choose to volunteer for this research study. This project will be conducted within the
      thermal physiology laboratory, complete with a climatic chamber (Cantrol, CES +13/+44)
      located within the Human Performance Laboratory (HPL) at the University of Connecticut. We
      expect data collection to take approximately 3-4 months for completion and each interested
      individual will complete all five trials included within the study design within a
      randomized, counterbalanced order.

      Participants will be randomly assigned de-identified codes, trial grouping orders, and
      allocation of amino acid rehydration beverages (i.e., aminoVITAL Rapid Recovery or Placebo)
      after approval has been provided and consent has been obtained. The order of participation
      will be counterbalanced between participants to ensure that there is not an order effect with
      each participant completing all 5 trials outlined in the study design. Additionally, for the
      post trial amino acid rehydration portion of the study only, participants will be matched
      based on an assortment of physiological variables measured (i.e., physical fitness [VO2max],
      body mass index, body surface area, age, height, and/or weight) in regards to their assigned
      allocation of the amino acid rehydration beverages (i.e., aminoVITAL Rapid Recovery or
      Placebo) that will be consumed during the recovery period of the study design.

      Environmental Conditions Session I as well as all Baseline Visits and matched-control 24-hour
      Rehydration Sessions (i.e., AminoVITAL Rapid Recovery or Placebo) will be completed within
      thermoneutral conditions. Moreover, all Dehydration Periods associated with completion of the
      study will be completed by the participant outside of the laboratory. Finally, all
      counterbalanced testing sessions (i.e., 0.8PR-Fluid, 0.4PR-Fluid, PLA-Fluid, 0.8PR-Dry, and
      PLA-Dry) will be conducted within the climatic chamber set to a climate with an ambient
      temperature at approximately 330C (91.40F) and relative humidity at approximately 25%.

      Baseline and VO2max Testing - Session 1 Session 1 will serve as a baseline testing session to
      obtain an assortment of physiological, vestibular, strength, and cognitive measurements to
      conduct an effective baseline measurement for each individual participating in this study.
      Physiological assessments will include measurements of each individual's body composition
      (height, weight, and body fat percentage), cardiovascular health (resting blood pressure,
      heart rate, and HRV), and aerobic fitness level via assessment of maximal oxygen consumption
      (VO2max). Furthermore, participants will be assessed for their cognitive abilities (ANAM
      testing battery), vestibular performance (BESS) and physical performance (grip strength and
      grip endurance). For the completion of this testing session, participants will be instructed
      to consume an efficient amount of fluids to ensure proper hydration for testing.
      Additionally, participants will be instructed to refrain from eating or smoking for up to 3
      hours before the beginning of their session.

      Arrival Procedures:

      Upon arrival, subjects will be asked if they have refrained from excluded nutritional
      supplementation for the last 48 hours, exercise and alcohol consumption in the past 24 hours,
      and caffeine for the last 12 hours. Next, subjects will provide their nude body mass and a
      urine sample within a clean urine cup for the assessment of urine specific gravity (USG) and
      urine color to determine hydration status. Privacy will be afforded for each participant
      while obtaining body mass measures by taking measurements with the participant alone in a
      private room and the research team member reading the scale outside of the room. Those with a
      USG <1.020 will be allowed to proceed with the exercise protocol. Those with a USG between
      1.020-1.025 will be given approximately 500ml of water for immediate consumption with the
      completion of an additional USG assessment to ensure participants are efficiently hydrated.
      Those with a USG >1.025 will be rescheduled for another day due to inadequate hydration. Upon
      completion participants will have their height measured via stadiometer and body composition
      assessed via air displacement plethysmography (BodPod®; Cosmed, Software Version 4.2+,
      Concord, CA, USA).

      Testing Procedures:

      Upon completion of all arrival procedures, participants will then be asked to don a heart
      rate strap and rest for approximately five minutes before having baseline cardiovascular
      measurements completed including resting heart rate variability (HRV), resting heart rate
      (HR), and blood pressure (BP). Afterwards, participants will then be asked to complete the
      baseline measurement for their cognitive performance battery which will include the
      completion of the Modified Balance Error Scoring System (BESS), hand grip strength and
      endurance and the ANAM testing battery. Afterwards, participants will then be asked to
      complete a maximal oxygen uptake (VO2max) test performed via running on a motorized treadmill
      within a thermoneutral environment. This assessment will be completed as a baseline
      assessment for the participant's aerobic fitness (VO2max test) and the results (i.e., minimum
      VO2max of 45 ml/kg/min) will be used as a final inclusionary criteria measurement for the
      participant. Please see the Measurements Completed section for further information regarding
      procedures completed when conducting these testing protocols.

      Testing of Biomedical Intervention - Climatic Chamber Testing Sessions Participants will be
      eligible to initiate the testing phase of their participation approximately 48 hours after
      the completion of all Session 1 baseline protocols. Furthermore, a minimum of 72 hours
      (approximately 3 days) must pass between the completion of each testing session completed.
      However, participants will be provided flexibility in scheduling through the option to
      reschedule testing sessions if needed to accommodate their personal schedules or rescheduling
      within the laboratory space. As previously outlined, the order of trials completed will be
      randomized to limit the possibility of an order effect for responses obtained to be detected.
      Each trial will include a predetermined amount (i.e., 0.8g/kg or 0.4g/kg) of the biomedical
      intervention (PR lotion or Placebo lotion) to be provided by the project sponsor.
      Differential amounts will be provided to investigate if a dose-dependent response may be
      elicited for the benefits of application regarding the biomedical intervention. For all
      trials, participants will undergo fluid restriction to attain hypohydration. Moreover,
      participants will arrive to the laboratory in a dehydrated state (protocols regarding this
      have been provided further below) and will either receive a pre-determined fluid bolus to
      replace a portion of their previous day's losses (relative to their body composition) or no
      fluid. This will allow us to assess the efficiency of the biomedical intervention for the
      retention of fluids consumed during their exposure to both passive and exertional heat stress
      while in a dehydrated state.

      Baseline Visits and Dehydration Periods To properly induce dehydration within study
      participants, they will be asked not to take in fluid or high fluid containing foods (i.e.,
      soup, cereal with milk, etc.) for approximately 18-24 hours prior to their scheduled Climatic
      Chamber Testing Session. However, before the initiation of this fluid restriction period,
      participants will be asked to arrive to the HPL for the completion of a pre-testing Baseline
      Visit that will need to be conducted before the beginning of each individual phase within the
      study. This session will include the collection of the participant's nude body weight in
      addition to a spot urine sample and a blood draw. The collection of the participant's nude
      body weight and urine sample will be conducted within the privacy of a restroom within the
      HPL. Additionally, a single blood draw will be conducted for the collection of approximately
      11 mL (~0.75 tablespoon) of blood. These measurements will be collected in order to provide a
      euhydrated baseline measurement to compare to the measurements collected at the beginning of
      each Climatic Chamber Testing Session to confirm that proper dehydration has been attained.
      At the completion of all the previously described tasks associated with this visit,
      participants will be provided a urine jug for the collection of a 24-hour urine sample which
      will be provided to the administrating research personnel upon arrival for their upcoming
      testing session. Additionally, participants will also be asked to consume a similar dietary
      intake between each lab visit (measured via completion of the dietary recall log), with the
      exception of fluid and high fluid containing foods. This time period has been designed to
      elicit an

      ~1.5-3.0% loss in body mass and has been performed previously in our laboratory (See UCONN
      IRB Protocol #H18-220, #H15-183, and #H10-043).

      Pre-Testing Procedures The initial Climatic Chamber Testing Session can be completed after
      approximately 48 hours have passed since the completion of all Session 1 baseline testing
      procedures. This time period would include the completion of both the phase specific Baseline
      Visit and Dehydration Period. Phases 2, 3, 4, and 5 will be completed approximately 24 hours
      the completion of their phase specific Baseline Visit where participants will be instructed
      to arrive at the HPL at the cessation of their Dehydration Period. Similar to Session 1,
      participants will be instructed to refrain from eating or smoking for up to 3 hours before
      the beginning of their testing session. Additionally, participants will be instructed to
      partake in an 18-24-hour fluid restriction period in order to exacerbate the dehydrated
      response to both passive and exertional heat stress. For testing sessions only, upon arrival
      participants will be asked to complete a nude body mass in private to confirm that they have
      achieved the desired level of dehydration from their baseline (~1.5-3%). In addition to the
      body mass loss, participants will also be asked to provide their 24-hour urine sample
      (collected during the dehydration period) and a spot urine sample. The spot urine sample will
      be used to confirm dehydration indicated by a USG >1.024, however this urinary measure will
      not exclude participation but rather confirm the participant's hydration status. Next, the
      participant will be asked to don a heart rate strap and provide their completed thirst scale
      and dietary recall log. Upon completion, resting cardiovascular measurements will be
      collected including HRV, HR, and BP. Once completed, the participant will complete the
      cognitive/performance battery which will include completion of the ANAM testing battery,
      BESS, and hand grip strength and endurance. Afterwards, participants will have a venous
      cannula inserted by an HPL trained research team member to allow for subsequent sampling of
      blood without the need for multiple needle sticks. Upon a successful insertion of the venous
      cannula a blood draw will be completed for the collection of 11 mL (~0.75 tablespoon) of
      blood. Afterwards, the participant will have the Nix Biosensor applied to the pre-determined
      location on their body (between the belly button and the rib cage) and will be provided the
      predetermined amount (i.e., 0.8g/kg or 0.4g/kg) of the biomedical intervention supplement
      (i.e., PR or Placebo Lotion) to be applied to their entire body (from neck to ankles) within
      the privacy of a restroom. Finally, prior to entering the environmental chamber, participants
      will be instructed to privately insert the rectal thermometer 10-15 cm beyond the anal
      sphincter for the continuous monitoring of core body temperature.

      Data Collection - Initial 95 minutes Once the subject has indicated they have successfully
      completed all required arrival procedures, they will then be permitted to enter the
      environmental chamber (~330C [91.40F], ~25% relative humidity) where they will be instructed
      to sit down at a desk provided and begin a 15-minute period of environmental equilibration.
      At the end of the environmental equilibration, identified as time point 0 in Figure 7, the
      participant will be asked to complete an HRV assessment before having another 11mL blood
      sample, nude body mass, and spot urine sample collected. Similar assessments will be
      completed at time point 40. At time point 80, similar assessments will be completed in
      addition to the cognitive battery (ANAM testing battery) and the performance battery (BESS
      and hand grip strength and endurance). Furthermore, 2 additional 3 mL blood samples (~1
      teaspoon total) will be collected at time points 20 and 60 of the protocol as illustrated in
      Figure 7. Finally, three equal fluid boluses will be provided for three of the proposed
      phases to be completed (0.8PR - Fluid, 0.4PR - Fluid, PLA - Fluid) at the 10-, 20-, and 30-
      minute marks as illustrated in Figure 7. The fluid bolus amount will be relative to the
      subject's body composition and will be enough to replace ~1% of the body mass lost between
      body mass measured on the intervention trial day and body mass measured during their initial
      baseline visit (Session 1). This fluid bolus will be provided for the assessment of fluid
      retention in regards to the biomedical intervention and its associated amount applied to the
      participant's body.

      Data Collection - 120-minute Exercise Protocol At the completion of all data collection
      procedures conducted at the 80-minute mark (i.e., passive heat stress), the participant will
      immediately be escorted to the treadmill for the initiation of their exercise protocol. The
      protocol will include the completion of aerobic exercise (walking or jogging) conducted at
      ~40% of the participant's velocity measured during the last stage of their baseline VO2max
      test (i.e., vVO2max). This portion of the protocol (i.e., exertional heat stress) will begin
      with the participant donning the Hans Rudolph mask which will be attached to a breathing tube
      for the measurement of expired air delivered to the metabolic cart system during the exercise
      protocol. Similar to measurements collected during the participant's baseline VO2max test,
      the metabolic cart will continuously measure respiratory exchange ratio (RER), oxygen
      consumption (VO2), and carbon dioxide production (VCO2) while being used by the participant.
      This assessment will be used during three separate 5-minute intervals at the 100-, 160-, and
      215-minute marks. Aerobic exercise completed between these time points will not require the
      subject to wear the Hans Rudolph mask as indicated in Figure 7. Using the previously inserted
      cannula, supplemental 3 mL blood draws will be completed at the 130- and 190-minute marks.
      Additionally, one 11 mL blood draw will be completed at the 220-minute time mark. Finally,
      assessments will be completed immediately after the completion of the exercise protocol and
      will include the assessment of the participant's nude body mass and collection of a spot
      urine sample in addition to assessment of the participants cardiovascular health (i.e., HR,
      HRV, and BP) and completion of the cognitive battery (ANAM testing battery) and performance
      tasks (BESS, hand grip strength, and hand grip endurance). Once all measurements have been
      collected the participant will be directed to exit the environmental chamber for the
      completion of their discharge from the HPL.

      Sub-study - 24-hour Rehydration Sessions At the completion of the participant's discharge
      procedures, the participant will initiate their 24-hour recovery period where the progression
      of their rehydration during the post-exercise recovery period will be compared between the
      provision of one of two amino acid rehydration beverages (i.e., AminoVITAL Rapid Recovery or
      Placebo). For the completion of comparisons between these two beverages, participants will be
      matched on demographical information pertaining to their aerobic fitness level (i.e.,
      VO2max), body mass index (BMI), body surface area (BSA), and/or age. Once identified, the
      beverage will be provided to the participant before the completion of each of their discharge
      protocols to ensure completion for the 24-hour follow-up session. Moreover, participants will
      be provided specific instructions pertaining to consistency in regards to their nutritional
      intake and fluid consumption over the 24-hour period following exercise until they are
      directed to come back to the HPL for the completion of follow-up testing procedures.

      Rehydration Protocol Before departing the HPL, participants will be provided four separate
      bags where each will include all of the following items: (1) one jug provided for the
      collection of urine throughout the predetermined time period; (2) one urine cup for the
      collection of a spot urine sample at the end of each predetermined time period; (3) two
      perceptual questionnaires (i.e., AD-ACL and CFS) for completion at the end of each
      predetermined time period; and (4) the predetermined nutritional supplement (AminoVITAL Rapid
      Recovery or Placebo) to be consumed at the beginning of each predetermined time period (See
      illustration of timeline in Figure 8). Participants will be instructed on storage of all
      materials and will be required to return all completed materials and collected biospecimens
      upon their return to the HPL approximately 24-hours after the completion of their testing
      session.

      Topical Solution Procedures Supplies containing the topical solution will be provided to the
      participant for application to their body within the privacy of a restroom. The amount of
      lotion provided for application will be dependent on the session completed (i.e., 0.8g/kg or
      0.4g/kg) and relative to the participant's body composition. To ensure the product usage
      adheres to the drug facts label provided, research team personnel will ensure that the bottle
      is well shaken prior to dispensing the lotion into the plastic bag. When it is time to apply
      the product to their body, the participant will be instructed to wash their hands before and
      after applying the product in addition to avoiding contact with any open orifices on their
      face (i.e., eyes, mouth, nose, etc.) until their hands have been washed. In efforts to keep
      the lotion from the participant's hands, the lotion will be provided within a plastic bag and
      the participant will be instructed to insert their hand into the opposite side of the bag
      while directly applying the lotion to the body from the bag. After the lotion has been
      appropriately applied, the participant will return the used bag to the research team member
      so that pre-application and post-application weight can be measured and compared for proper
      assessment of lotion amount applied to the skin. Participants will be instructed to apply the
      solution primarily to areas of their lower extremities (i.e., thighs, hamstrings, calves,
      buttocks, etc.) in addition to their lower back, arms, midsection, and/or chest if enough
      solution is available. Application will be considered complete when the solution has been
      transmitted to the skin in a fashion where no residue from the lotion is visible by
      researchers from the skin of the participant.

      Collection of Urine Samples and Body Weight Measurements For the collection of all urine spot
      samples, researchers will provide a clean cup and top to seal the capsule. Participants will
      be asked to provide a sample regardless of urgency to urinate at specific time points during
      the trial. If the participant is unable to provide a sample at the time point requested, no
      protocol deviation will be considered as the lack in sample provided will still be used
      towards the completion of data analysis. Furthermore, if the participant must provide a urine
      sample without being requested by a research team member, any urine expelled will be added to
      the amount collected (if any) during the next urine sample collection time point.
      Additionally, participants will be instructed to complete a measurement of nude body weight
      completed before the provision of a urine sample. Both the collection of urine samples and
      measurement of body weight will be completed within the privacy of a bathroom.
    

Intervention name(s): PR Lotion - AMP Human Performance; Placebo Lotion; AminoVital - Rapid Recovery; Placebo Supplement
Intervention type(s): Other; Other; Other; Other
Intervention description(s): Sodium Bicarbonate Topical Solution. For use of the PR Lotion solution, consumers are instructed to apply the lotion to areas of the body that have been identified as most likely to use during their activity (i.e. calves and thighs for runners, shoulders and forearms for swimmers, etc.). Moreover, the product can be applied up to 2 hours prior to beginning a workout or event with one use supporting a 4-6 hour workout. AMP Human has also verified the safety of their product as being well tolerated in consumers >2 years of age unless there is a known allergy to an ingredient on the label. Moreover, to the company's knowledge no side effects have been reported per the SAFETY Section at https://amphuman.com/pages/faq.
Other Names:
NDC Code: 72358-101-01 NDC Code: 72358-101-02 NDC Code: 72358-101-03; Placebo Topical Solution. Lotion will be created by the AMP Human Performance company and will include all ingredients similar to the PR Lotion product except for the exclusion of sodium bicarbonate.; AminoVITAL Rapid Recovery is a commercially available supplement that is not currently regulated by the FDA but does complete both internal quality control and third-party testing for all of their products. AminoVITAL Rapid Recovery has been certified by the Banned Substance Control Group (BSCG; https://www.bscg.org/certified-drug- free-supplements/?AminoVITAL) and has been certified to be free of 496+ drugs including WADA Prohibited Substances as well as prescription, over the counter, and illicit drugs not banned in sport. AminoVITAL Rapid Recovery is safe to consume multiple times within a single day and has been found most effective when taken within 30 minutes of cessation of exercise. No known side effects are associated with the ingestion of aminoVITAL Rapid Recovery; however, side effects of amino acid toxicity include gastrointestinal distress, nausea and headache.; Supplement will be created by the aminoVITAL company and will include all ingredients similar to the commercially available Rapid Recovery product except for the exclusion of the amino acid blend.
Other intervention name(s): NDC Code: 72358-101-01; NDC Code: 72358-101-02; NDC Code: 72358-101-03
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Sodium Bicarbonate; Amino Acid Supplementation; Topical Lotion; Renal Injury