Evaluation of the Attenuation by Aes-103 of Hypoxia Mediated Decrements in Endurance Exercise Performance
Condition: Hypoxia
MeSH terms: Hypoxia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      In low oxygen environments, such as high-altitude, some adults may become ill and suffer from
      acute mountain sickness. Further, all adults will find that exercising becomes much more
      difficult when compared with exercise at lower altitudes (e.g. sea-level). The purpose of
      this investigation is to study the effects of a new medicine called Aes-103. A company called
      AesRx, LLC makes this medicine. The active ingredient in the medicine is
      5-Hydroxymethyl-2-Furfural (5HMF), a naturally occurring substance that can be found in
      coffee, honey, dried fruits, fruit juices, malt, barley, Balsamic vinegar and caramel.The
      investigators believe that Aes-103 may help people adjust to high-altitude quickly and
      prevent them from becoming ill. The purpose of the study is to determine if Aes-103 will
      promote endurance performance in low oxygen environments in healthy adult humans.

      Aes-103 is currently being investigated by AesRx, LLC (Newton, MA) in collaboration with the
      National Heart, Lung and Blood Institute of the NIH (Bethesda, MD) as a potential
      anti-sickling agent in sickle cell disease. Sickle-cell disease is characterized by problems
      in blood that prevent blood cells from carrying oxygen. Aes-103 might be able to help blood
      cells carry more oxygen. It is for this reason that the investigators in this study believe
      Aes-103 might help people adjust to high-altitude quickly.

      There are no known special safety considerations with the active ingredient in Aes-103
      (5-HMF). In recent, placebo controlled, clinical safety tests, Aes-103 was given in single
      doses of 300 mg, 1000 mg,2000 mg and 4000 mg to healthy normal volunteers. Additionally, the
      toxicological effects of Aes-103 have been studied when given acutely, sub-acutely, and
      chronically in rodents, and for up to 28 days in dogs. Based on these safety studies, single
      doses of Aes-103 are expected to have no significant negative/toxicological effect at the
      doses being evaluated in this study.
    

Detailed description: 
      This is a randomized, placebo-controlled, double-blind blind, repeated measures (cross-over)
      study. Approximately 12 healthy adult men will consume, in a random order, a placebo prior to
      exercise in normoxia, a placebo prior to exercise in hypoxia, 1000 mg of Aes-103 prior to
      exercise in hypoxia, and 3000 mg of Aes-103 prior to exercise in hypoxia.

      Study participants will report to the Human Performance/Clinical Research Laboratory (HPCRL)
      on 6 separate occasions. On visit 1 study participants will undergo screening (e.g. medical
      history and 12-lead electrocardiogram and blood pressure at rest and during incremental
      exercise to volitional exhaustion), and will be instructed to avoid foods and drinks high in
      5-HMF (e.g., coffee, malt, barley, dried fruits, and caramel) for at least 3 days before each
      subsequent visit. Visit 2 will comprise of a habituation visit during which subjects will be
      given the opportunity to rehearse the exercise test. Visits 3, 4, 5 and 6, will occur in a
      random order and be almost identical in nature. Study participants will abstain from vigorous
      physical exercise and alcohol consumption during the 24-hours prior to each visit. In
      addition, study participants will abstain from all food and beverages, except water, during
      the 4-hours prior to visits 3, 4, 5 and 6. On arrival subjects will be instrumented for
      measurement of heart rate, blood pressure and blood oxygen saturation. Following baseline
      determination subjects will consume either: a placebo, 1000 mg of Aes-103 or 3000 mg of
      Aes-103. 45 minutes after consumption, participants will enter our environmental chamber,
      adjusted randomly to either normoxia (21% oxygen) or hypoxia (15% oxygen). The pairing of
      normoxia/hypoxia and supplement will be as follows: placebo + normoxia, placebo + hypoxia,
      1000 mg + hypoxia, and 3000 mg + hypoxia. Participants will remain seated in the
      environmental chamber for 15 minutes, after which they will complete a standardized warm-up
      bout of exercise (100 W for 30 minutes) followed by a brief time trial (time taken to cycle
      12.5 km (~7.75 miles)). Heart rate, blood pressure and blood oxygen saturation will be
      recorded every 5 minutes. During exercise, subjective ratings of perceived exertion (Borg
      Scale) will be recorded every 10 minutes, and at end-exercise.
    

Intervention name(s): Placebo; Aes-103; Aes-103
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 100 mL; Single dose of 1000mg Aes-103 dissolved in 100 mL of Tropicana Pure Premium Orange Juice; Single dose of 3000mg Aes-103 dissolved in 100 mL of Tropicana Pure Premium Orange Juice
Other intervention name(s): Tropicana Pure Premium Orange Juice; 5-Hydroxymethyl-2-Furfural (5-HMF); 5-Hydroxymethyl-2-Furfural (5-HMF)
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: 5 Hydroxymethyl 2 Furfural; AES103; Exercise