Evaluation of the Attenuation by Aes-103 of Hypoxia Mediated Decrements in Endurance Exercise Performance

• Sponsor: Colorado State University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01871142
• Collaborator: AesRx, LLC (Industry)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 15
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hypoxia	Drug: Placebo; Drug: Aes-103; Drug: Aes-103	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Double-Blind, Placebo Controlled Evaluation of the Attenuation by Aes-103 of Hypoxia Mediated Decrements in Endurance Exercise Performance in Healthy Adult Humans
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Randomized crossover assignment Participants will receive, 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. Each intervention is separated by a 7 day washout period.	Drug: Placebo; 100 mL; Other Names: Tropicana Pure Premium Orange Juice ; Drug: Aes-103; Single dose of 1000mg Aes-103 dissolved in 100 mL of Tropicana Pure Premium Orange Juice; Other Names: 5-Hydroxymethyl-2-Furfural (5-HMF) ; Drug: Aes-103; Single dose of 3000mg Aes-103 dissolved in 100 mL of Tropicana Pure Premium Orange Juice; Other Names: 5-Hydroxymethyl-2-Furfural (5-HMF)

Outcome Measures

Primary Outcome Measures

1. Primary Objective Endurance Exercise Performance [The time trial will begin after 1 hour after consumption of the intervention or placebo under normoxic or hypoxic conditions.]

   To quantify endurance exercise performance (time trial performance during stationary cycle ergometer exercise) in healthy adult men in four conditions: normoxia (normal oxygen; fraction of inspired oxygen = 0.21) following oral placebo consumption, hypoxia (low oxygen; fraction of inspired oxygen = 0.15) following oral placebo consumption, hypoxia following oral consumption Aes-103 (1000 mg) and hypoxia following oral consumption Aes-103 (3000 mg).

Secondary Outcome Measures

1. Secondary Objective Safety and Tolerability [AEs will be monitored at the time of visit and during the follow up period of 7 to 14 days.]

   To assess the safety and tolerability of single, escalating oral doses of Aes-103 compared with placebo in healthy adult men at rest and during stationary cycle ergometer exercise in normoxia and hypoxia by monitoring adverse events (AEs), electrocardiograms (ECGs), blood pressure, blood oxygen saturation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Be a healthy male volunteer, aged 18-40 years old, body mass index 18-30 kg/m2, inclusive

• Have successfully completed a screening visit consisting of medical history, physical examination, 12-lead ECG, blood pressure, blood oxygen saturation at rest and during incremental exercise to volitional exhaustion (Note: Subjects with abnormal screening values may be eligible if the results are not clinically significant, as judged by the investigator or medical monitor)

• Be able to understand and have provided written informed consent including signature on an informed consent form approved by an institutional review board

• Have provided written authorization for use and disclosure of protected health information

• Agree to abide by the study schedule and dietary restrictions and to return for the required assessments

• Be willing to abstain from foods high in 5-HMF (e.g., coffee, malt, barley, balsamic vinegar, dried fruits,and caramel products) for at least 3 days prior to each dosing

• Be willing and able to repeatedly perform exhaustive cycle ergometer exercise

Exclusion Criteria:

• Have evidence of clinically significant cardiovascular, respiratory, renal, hepatic, pulmonary, gastrointestinal, hematological, neurological, psychiatric, or other disease that may interfere with the objectives of the study or the safety of the subject, as judged by the investigator in agreement with the sponsor or medical monitor, have been hospitalized in the past 2 years as a result of these conditions, or are receiving pharmacological treatment for these conditions

• Have taken prescription drugs or herbal preparations in the 2 weeks before dosing

• Is currently enrolled in another clinical study for another investigational drug or has taken any other investigational drug within 30 days before the screening visit

• Habitual and/or recent use of recreational drugs, such as cocaine, marijuana, opiates, amphetamines, methamphetamines, benzodiazepines,

• Have taken disulfiram, 4-methylpyrazole, or any other drug that is an inhibitor of alcohol dehydrogenase or aldehyde dehydrogenase within the past 30 days

• Have engaged in strenuous physical activity within 24 hours prior to dosing

• Be considered not suitable for participation in this trial for any reason, as judged by the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colorado State University, Dept. of Health and Exercise Science	Fort Collins	Colorado	United States	80523-1582

Sponsors and Collaborators

• Colorado State University
• AesRx, LLC

Investigators

• Principal Investigator: Christopher Bell, PhD, Colorado State University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Department of Health and Exercise Science, Colorado State University
• Initial Safety Trial For Treatments Under Investigation In Current Study

Publications

None provided.

• Responsible Party: Christopher Bell, Associate Professor, Colorado State University
• ClinicalTrials.gov Identifier: NCT01871142
• Other Study ID Numbers: 13-4002H
• First Posted: Jun 6, 2013
• Last Update Posted: Oct 24, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Christopher Bell, Associate Professor, Colorado State University: 5 Hydroxymethyl 2 Furfural; AES103; Exercise
• Additional relevant MeSH terms: Hypoxia

Study Results

Participant Flow

Arm/Group Title	Randomized Crossover Assignment
Arm/Group Description	Participants will receive, 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. Each intervention is separated by a 7 day washout period.
Period Title: Overall Study
STARTED	12
Received Placebo + Normoixa	11
Received Placebo + Hypoxia	12
Received 1000mg Aes 103+ Hypoxia	11
Received 3000mg Aes-103 + Hypoxia	12
COMPLETED	11
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	All enrolled participant baseline data
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27 (6)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	12 100%
Region of Enrollment (participants) [Number]
United States	12 100%
Height (meters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters]	1.75 (0.03)
Body Mass (kg) (Kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms]	74.8 (6)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24.3 (2)
Fat Mass (kg) (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	14.1 (4)
Lean Mass (kg) (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	56.7 (5)
Percent Body Fat (Percentage of body fat) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of body fat]	19 (4)
Waist Circumference (cm) (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	79.3 (5)
Waist-to-Hip Ratio (ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ratio]	79.3 (0.04)
Maximal oxygen uptake (VO2max (L/min)) (Liters/minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liters/minute]	3.96 (0.06)
VO2max (ml/kg/min) (milliliter/kilogram/minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliliter/kilogram/minute]	53.2 (8)
Maximal heart rate (HRmax (beats/min)) (Beats/minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Beats/minute]	187 (4)
Maximal respiratory exchange ratio (RERmax) (VCO2/VO2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [VCO2/VO2]	1.09 (0.02)

Outcome Measures

1. Primary Outcome

Title	Primary Objective Endurance Exercise Performance
Description	To quantify endurance exercise performance (time trial performance during stationary cycle ergometer exercise) in healthy adult men in four conditions: normoxia (normal oxygen; fraction of inspired oxygen = 0.21) following oral placebo consumption, hypoxia (low oxygen; fraction of inspired oxygen = 0.15) following oral placebo consumption, hypoxia following oral consumption Aes-103 (1000 mg) and hypoxia following oral consumption Aes-103 (3000 mg).
Time Frame	The time trial will begin after 1 hour after consumption of the intervention or placebo under normoxic or hypoxic conditions.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palcebo + Normoxia	Placebo + Hypoxia	1000mg Aes-103 + Hypoxia	3000mg Aes-103 + Hypoxia
Arm/Group Description	Randomized crossover assignment for each participant. Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Normoxia (21% oxygen)	Randomized crossover assignment for each participant. Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Hypoxia (15% Oxygen)	Randomized crossover assignment for each participant. Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Hypoxia (15% oxygen)	Randomized crossover assignment for each participant. Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Hypoxia (15% oxygen)
Measure Participants	11	11	11	11
Mean (Standard Error) [minutes]	22.4 (0.7)	24.5 (0.5)	24.0 (0.7)	24.6 (0.6)

2. Secondary Outcome

Title	Secondary Objective Safety and Tolerability
Description	To assess the safety and tolerability of single, escalating oral doses of Aes-103 compared with placebo in healthy adult men at rest and during stationary cycle ergometer exercise in normoxia and hypoxia by monitoring adverse events (AEs), electrocardiograms (ECGs), blood pressure, blood oxygen saturation.
Time Frame	AEs will be monitored at the time of visit and during the follow up period of 7 to 14 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo + Normoxia	Placebo + Hypoxia	1000mg Aes-103 + Hypoxia	3000mg Aes-103 + Hypoxia
Arm/Group Description	Number of participants receiving placebo in normoxic conditions. Randomized crossover assignment for each participant. Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Normoxia (21% oxygen)	Number of participants receiving placebo in hypoxic conditions Randomized crossover assignment for each participant. Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Normoxia (21% oxygen)	Number of participants receiving 1000mg Aes-103 in hypoxic conditions Randomized crossover assignment for each participant. Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Hypoxia (15% oxygen)	Number of participants receiving 3000mg Aes-103 in hypoxic conditions Randomized crossover assignment for each participant. Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Hypoxia (15% oxygen)
Measure Participants	11	12	11	12
Number [participants]	0 0%	0 NaN	0 NaN	1 NaN

Adverse Events

Time Frame	1 day
Arm/Group Title	Placebo + Normoxia		Placebo + Hypoxia		1000 mg Aes-103 + Hypoxia		Hypoxia 3000 mg Aes-103 + Hypoxia
Arm/Group Description	Participants receiving placebo in normoxic conditions Randomized crossover assignment for each participant. Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Normoxia (21% oxygen)		Participants receiving placebo in Hypoxic conditions Randomized crossover assignment for each participant Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Hypoxia (15% Oxygen)		Participants receiving 1000mg Aes-103 in hypoxic conditions Randomized crossover assignment for each participant. Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Hypoxia (15% oxygen)		Participants receiving 3000mg Aes-103 in hypoxic conditions Randomized crossover assignment for each participant. Intervention 1 dose. Next random crossover assignment was followed by a 7 day washout period. Note: Hypoxia (15% oxygen
All Cause Mortality
	Placebo + Normoxia		Placebo + Hypoxia		1000 mg Aes-103 + Hypoxia		Hypoxia 3000 mg Aes-103 + Hypoxia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo + Normoxia		Placebo + Hypoxia		1000 mg Aes-103 + Hypoxia		Hypoxia 3000 mg Aes-103 + Hypoxia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/12 (0%)		0/11 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Placebo + Normoxia		Placebo + Hypoxia		1000 mg Aes-103 + Hypoxia		Hypoxia 3000 mg Aes-103 + Hypoxia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/12 (0%)		0/11 (0%)		1/12 (8.3%)
General disorders
Nausea leading to vomiting	0/11 (0%)	0	0/12 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.