Acute Mountain Sickness and FatiguePhase 1GQ02NCT01794078
A Study to Test the Safety of Combined Dosing With Aminophylline and Ambrisentan in Exercising Healthy Human Volunteers at Simulated High Altitude
A Phase 1 study testing Aminophylline 400 mg and Ambrisentan 5 mg in people with Acute Mountain Sickness and Fatigue, run by Robert J Noveck, M.D. at 2 sites in United States.
Trial summary
Acute exposure of the unacclimatized human body to high altitude leads to health complications, such as loss of exercise performance capacity and fatigue. The investigators have found that the combination of the xanthine drug theophylline and the endothelin receptor antagonist ambrisentan improves the exercise… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Mountain Sickness and Fatigue
- What is being tested?
- Aminophylline 400 mg and Ambrisentan 5 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2013to Dec 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must give written Informed Consent to participate in the study prior to undergoing any screening procedures. The subject will be given a signed and dated copy of the Informed Consent.
- Subjects must be healthy non-smoking (for 6 months or greater at commencement of Cycle 1) adult male and female volunteers; at least 18 through 50 years at screening, with a BMI of 18-33 kg/m2 and weighing at least 143 lbs. (65 kg). Subjects' health status will be determined by the medical history, physical examination, vital signs, ECG, blood chemistry, hematology, and urinalysis performed at screening.
- Subjects must be willing to fast a minimum of 2 hours prior to screening.
- Subjects must be willing to abstain from alcohol and xanthine-containing food and beverages from 48 hours before check-in for each study day,
- Women who are of non-childbearing potential, must be:
- Surgically sterile (removal of both ovaries and/ or uterus at least 12 months prior to dosing) and with an FSH level at screening of ≥ 40 mIU/mL.
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- Naturally postmenopausal (spontaneous cessation of menses) for at least 24 consecutive months prior to dosing on Day -1, and with an FSH level at screening of ≥ 40 mIU/mL.
- Women of child-bearing potential must have a negative serum or urine pregnancy test at screening, during the study, and must agree to avoid pregnancy during study and for three months after the last dose of study drug. Pregnancy is tested at screening, during check-in of each testing cycle, during the follow-up visit, and at any given point if deemed necessary to the PI or designate. During treatment, women of child-bearing potential must use two acceptable methods of contraception at the same time unless the subject has had a documented tubal sterilization or chooses to use a Copper T 380A IUD or LNG 20 IUS, in which case no additional contraception is required. Abstinence is not considered a form of contraception. Medically acceptable contraceptives include: (1) documented surgical sterilization (such as a hysterectomy), (2) barrier methods (such as a condom or diaphragm) used with a spermicide, or (3) an intrauterine device (IUD) or intrauterine system (IUS).
- Male subjects must agree to take all necessary measures to avoid causing pregnancy in their sexual partners during the study and for three months after the last dose of study drug. Medically acceptable contraceptives include: (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicidal. Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use.
- Subjects must agree not to donate blood, platelets, or any other blood components 30 days, or plasma 90 days, prior to consenting and for 1 month after the last dose.
- Male subjects must agree not to donate sperm during the study and for 12 weeks after the last dose.
Who cannot join
- Subjects with laboratory results outside the normal range, if considered clinically significant (CS) by the PI or delegate. In addition, subjects must have a hemoglobin concentration of ≥ 12.0 g/dL.
- A mental capacity that is limited to the extent that the subject cannot provide legal consent or understand information regarding the side effects of the study drug.
- Currently abusing drugs or alcohol or with a history of drug or alcohol abuse within the past two years.
- Unwillingness or lack of ability to comply with the protocol, or to cooperate fully with the PI and site personnel.
- Use of any of the following:
- Any concomitant medication including oral contraceptive hormones. Subjects who have received any prescribed or non-prescribed (over-the-counter [OTC]) systemic medication, topical medications, or herbal supplements within 14 days from Day 1. St. John's Wort (hypericin) must not have been taken for at least 30 days prior to Cycle 1, Day 1.
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- Any drugs, foods or substances known to be strong inhibitors or strong inducers of CYP enzymes (also known as cytochrome P450 enzymes); especially CYP 1A2, or Pgp within 7 days prior to Cycle 1, Day 1.
- Clinically significant ECG abnormality in the opinion of the PI or delegate.
- Vital signs or clinically significant laboratory values at the screening visit that in the opinion of the PI or delegate would make the subject an inappropriate candidate for the study.
- A VO2 max value of less than 42 mL/kg/min, as determined during exercise testing at screening. This value represents an educated estimate, and may be changed, to include new information, at the discretion of the PI.
- A history of, or otherwise indicated predisposition for, claustrophobia, i.e. the fear of closed, narrow spaces (because of the limited size of the high altitude chamber).
- A history of "undeserved" altitude sickness, i.e. altitude sickness at only moderate altitude. This would consist of altitude-related headaches, dizziness, or nausea during plane rides, or when traveling to moderately elevated locations of less than 2,743.2 meters/ 9,000 ft
- Has taken any other investigational drug during the 30 days prior to the screening visit or is currently participating in another investigational drug clinical trial.
- Made any significant donation or have had a significant loss of blood within 30, or donated plasma within 90 days of consenting.
- Receipt of a transfusion or any blood products within 90 days prior to commencement of Cycle 1
- History or manifestation of clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematologic or other medical disorders. For the purpose of the study, individual fitness and health are more important than family history of disease burden as a criterion for participation. For example, an individual may have significant family history of cardiovascular disease; however, the individual subject's active lifestyle makes a manifestation of such disease at young ages unlikely. To account for such expected variation, the ultimate decision whether to exclude or include an individual based on family history or manifestation of disease will be made by the PI. The PI may choose to use physiological assessments, such as e.g. ECG, blood pressure, and VO2 max fitness level as an aid for decision making.
- Any condition that might interfere with the absorption of the study medications or influence the interpretation of the results of the study.
- Subjects who are carriers of the Hepatitis B surface antigen (HbsAg), Hepatitis C antibody, or HIV antibody.
- Serious mental or physical illness within the past year.
- Male subjects who consume more than 28 units of alcohol per week and female subjects who consume more than 21 units of alcohol per week (one unit of alcohol equals 250 mL of beer, 100 mL of a medium glass of wine, or 25 mL of spirits) or those subjects who have a significant history of alcoholism or drug/ chemical abuse within the last 2 years.
- Failure to agree to abstain from alcohol, cola, tea, coffee, chocolate and other caffeinated drink/ food from 48 h before check-in for Cycles 1 \& 2.
- Subjects who have used tobacco products or nicotine-containing products (including smoking cessation aids, such as gums or patches) within 6 months prior to commencement of Cycle 1
- Women of childbearing potential who are pregnant (as based on test results) or are breast feeding
- Subjects who have a history of hypersensitivity or idiosyncratic reaction to any of the products administered during the study.
- Subjects who, in the opinion of the PI (or delegate), should not participate in the study.
- Subjects who are employed by the Duke Clinical Research Unit and/or the Duke Hypobaric/ Hyperbaric Center
- Subjects who have a history of unexplained syncope or fainting from the collection of blood; i.e., autonomic dysfunction.
- Subjects who have a history of hypotension, including orthostatic hypotension. The ultimate decision about exclusion or inclusion of a potential subject is made by the PI.
- Lack of ability to understand verbal and/ or written English.
- History of clinically significant illness within 4 weeks prior to commencement of Cycle 1. In case a subject develops an illness between any of the study activities (Screening, Cycle 1, and Cycle 2), the subject may be removed from the study, if it deems appropriate and/ or necessary to the PI.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Duke Center for Hyperbaric Medicine
Durham, North Carolina, 27710
Duke Clinical Research Unit (DCRU)
Durham, North Carolina, 27710
About this study
Official title: A Randomized, 4-Sequence, Double-Blind Study to Test the Safety of Combined Dosing With Aminophylline and Ambrisentan in Exercising Healthy Human Volunteers at Simulated High Altitude
Acute exposure of the unacclimatized human body to high altitude leads to health complications, such as loss of exercise performance capacity and fatigue. The investigators have found that the combination of the xanthine drug theophylline and the endothelin receptor antagonist ambrisentan improves the exercise performance capacity of rats under simulated high altitude. In young, healthy human volunteers, this combination of drugs has not increase toxicity over the single compounds under sea-level conditions. The aim of this study is to test whether the combination of theophylline, supplied as its more soluble formulation aminophylline, and ambrisentan, are also safe to take under simulated high altitude of 4,267 meters, under both resting and exercising conditions. The study also aims to test whether this drug combination improves exercise capacity in humans. In this study, human subjects will be randomized to one of four treatment sequences and receive the same study drug(s) throughout all procedures. The study consists of an initial exercise test, followed by two cycles of drug testing at simulated high altitude: Cycle 1 - resting subjects receiving study drug at simulated altitude and continually monitored for safety with pharmacodynamic and pharmacokinetic assessments; and Cycle 2, the same as Cycle 1, with the addition of exercise testing. It is hypothesized that the combination of aminophylline and ambrisentan is not only safe under simulated high altitude, but also improves exercise performance capacity, in comparison with placebo.
- Conditions
- Acute Mountain Sickness and Fatigue
- Being tested
- Aminophylline 400 mg, Ambrisentan 5 mg, Placebo
- Keywords
- Acute Mountain Sickness, High altitude induced fatigue
- Medical subject headings
- Altitude Sickness, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aminophylline 400 mgDrug
Also called Mixture of theophylline and ethylene diamine
Xanthine derivative
Ambrisentan 5 mgDrug
Also called Letairis, Volibris
Endothelin receptor antagonist
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Oral placebo, administered as single dose during simulated altitude episodes Cycle 1 and Cycle 2 Receives: Other: Placebo |
| Aminophylline 400 mg | Experimental | Oral aminophylline 400 mg, administered as single dose during simulated altitude episodes Cycle 1 and Cycle 2 Receives: Drug: Aminophylline 400 mg |
| ambrisentan 5 mg | Experimental | Oral ambrisentan 5 mg, administered as single dose during simulated altitude episodes Cycle 1 and Cycle 2 Receives: Drug: Ambrisentan 5 mg |
| Combined aminophylline 400 mg and ambrisentan 5 mg | Experimental | Oral combined aminophylline 400 mg and ambrisentan 5 mg, administered as single doses during simulated altitude episodes Cycle 1 and Cycle 2 Receives: Drug: Aminophylline 400 mg; Drug: Ambrisentan 5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of combined or single-dose aminophylline and ambrisentan at simulated high altitude in resting human subjects
Incidence and severity of Adverse Events, blood pressure, heart rate, ECGs, blood oxygen saturation (pulse oximetry), symptoms related to early acute mountain sickness (AMS)
Measured: Safety endpoints will be measured during an episode of simulated high altitude (Cycle 1), at least 7 days post screening
The safety of combined or single-dose aminophylline and ambrisentan at simulated altitude in exercising human subjects
Incidence and severity of Adverse Events, blood pressure, heart rate, ECGs, blood oxygen saturation (pulse oximetry), symptoms related to acute mountain sickness (AMS)
Measured: Safety endpoints will be measured during simulated high altitude (Cycle 2) at least 22 days post screening
Secondary outcomes (2)
The efficacy of combined aminophylline and ambrisentan to improve exercise capacity under simulated high altitude
Exercise capacity is measured as the self-chosen level of exercise burden during cycling on a bicycle ergometer
Measured: Drug effects on exercise capacity are assessed during an episode of simulated high altitude (Cycle 2), at least 22 days after screening
The influence of simulated high altitude on pharmacokinetic profiles and drug interaction of aminophylline and ambrisentan
PK profiles will be compared between combined and single-dosed subjects
Measured: Blood samples for drug interaction analysis are acquired during an episode of simulated high altitude (Cycle 1), at least 7 days past screening
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2013 (estimated)
- Study startSep 2013
- Primary completionSep 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Mountain Sickness and FatigueStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Robert J Noveck, M.D.
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor-investigator, Robert J Noveck, M.D., Duke University
- Investigators
- Robert J Noveck, MD, PhD, Principal investigator, Duke UniversityClaude A Piantadosi, MD, Study director, Duke UniversityThies Schroeder, PhD, Study director, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01794078
- Sponsor's protocol ID
- Pro00037605
- Acronym
- GQ02
- Status last verified
- Nov 2015
- First submitted
- 10 Feb 2013
- Last updated
- 13 Nov 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, 4-Sequence, Double-Blind Study to Test the Safety of Combined Dosing With Aminophylline and Ambrisentan in Exercising Healthy Human Volunteers at Simulated High Altitude
- ClinicalTrials.gov ID
- NCT01794078
- Acronym / sponsor ID
- GQ02 / Pro00037605
- Conditions
- Acute Mountain Sickness and Fatigue
- Keywords
- Acute Mountain Sickness, High altitude induced fatigue
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Robert J Noveck, M.D.University, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- Sep 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 18 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute exposure of the unacclimatized human body to high altitude leads to health complications, such as loss of exercise performance capacity and fatigue. The investigators have found that the combination of the xanthine drug theophylline and the endothelin receptor antagonist ambrisentan improves the exercise performance capacity of rats under simulated high altitude. In young, healthy human volunteers, this combination of drugs has not increase toxicity over the single compounds under sea-level conditions. The aim of this study is to test whether the combination of theophylline, supplied as its more soluble formulation aminophylline, and ambrisentan, are also safe to take under simulated high altitude of 4,267 meters, under both resting and exercising conditions. The study also aims to test whether this drug combination improves exercise capacity in humans. In this study, human subjects will be randomized to one of four treatment sequences and receive the same study drug(s) throughout all procedures. The study consists of an initial exercise test, followed by two cycles of drug testing at simulated high altitude: Cycle 1 - resting subjects receiving study drug at simulated altitude and continually monitored for safety with pharmacodynamic and pharmacokinetic assessments; and Cycle 2, the same as Cycle 1, with the addition of exercise testing. It is hypothesized that the combination of aminophylline and ambrisentan is not only safe under simulated high altitude, but also improves exercise performance capacity, in comparison with placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Other: PlaceboOral placebo, administered as single dose during simulated altitude episodes Cycle 1 and Cycle 2 |
| Aminophylline 400 mg | Experimental | Drug: Aminophylline 400 mgOral aminophylline 400 mg, administered as single dose during simulated altitude episodes Cycle 1 and Cycle 2 |
| ambrisentan 5 mg | Experimental | Drug: Ambrisentan 5 mgOral ambrisentan 5 mg, administered as single dose during simulated altitude episodes Cycle 1 and Cycle 2 |
| Combined aminophylline 400 mg and ambrisentan 5 mg | Experimental | Drug: Aminophylline 400 mg, Drug: Ambrisentan 5 mgOral combined aminophylline 400 mg and ambrisentan 5 mg, administered as single doses during simulated altitude episodes Cycle 1 and Cycle 2 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Subjects must give written Informed Consent to participate in the study prior to undergoing any screening procedures. The subject will be given a signed and dated copy of the Informed Consent.
- Subjects must be healthy non-smoking (for 6 months or greater at commencement of Cycle 1) adult male and female volunteers; at least 18 through 50 years at screening, with a BMI of 18-33 kg/m2 and weighing at least 143 lbs. (65 kg). Subjects' health status will be determined by the medical history, physical examination, vital signs, ECG, blood chemistry, hematology, and urinalysis performed at screening.
- Subjects must be willing to fast a minimum of 2 hours prior to screening.
- Subjects must be willing to abstain from alcohol and xanthine-containing food and beverages from 48 hours before check-in for each study day,
- Women who are of non-childbearing potential, must be:
Key exclusion criteria (30 listed)
- Subjects with laboratory results outside the normal range, if considered clinically significant (CS) by the PI or delegate. In addition, subjects must have a hemoglobin concentration of ≥ 12.0 g/dL.
- A mental capacity that is limited to the extent that the subject cannot provide legal consent or understand information regarding the side effects of the study drug.
- Currently abusing drugs or alcohol or with a history of drug or alcohol abuse within the past two years.
- Unwillingness or lack of ability to comply with the protocol, or to cooperate fully with the PI and site personnel.
- Use of any of the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aminophylline 400 mgAlso: Mixture of theophylline and ethylene diamineXanthine derivative | Drug | Aminophylline 400 mg, Combined aminophylline 400 mg and ambrisentan 5 mg |
| Ambrisentan 5 mgAlso: Letairis, VolibrisEndothelin receptor antagonist | Drug | Combined aminophylline 400 mg and ambrisentan 5 mg, ambrisentan 5 mg |
| Placebo | Other | Control |
Primary outcome
The safety of combined or single-dose aminophylline and ambrisentan at simulated high altitude in resting human subjects
Time frame: Safety endpoints will be measured during an episode of simulated high altitude (Cycle 1), at least 7 days post screening
Incidence and severity of Adverse Events, blood pressure, heart rate, ECGs, blood oxygen saturation (pulse oximetry), symptoms related to early acute mountain sickness (AMS)
The safety of combined or single-dose aminophylline and ambrisentan at simulated altitude in exercising human subjects
Time frame: Safety endpoints will be measured during simulated high altitude (Cycle 2) at least 22 days post screening
Incidence and severity of Adverse Events, blood pressure, heart rate, ECGs, blood oxygen saturation (pulse oximetry), symptoms related to acute mountain sickness (AMS)
2 secondary outcomes
The efficacy of combined aminophylline and ambrisentan to improve exercise capacity under simulated high altitude
Time frame: Drug effects on exercise capacity are assessed during an episode of simulated high altitude (Cycle 2), at least 22 days after screening
The influence of simulated high altitude on pharmacokinetic profiles and drug interaction of aminophylline and ambrisentan
Time frame: Blood samples for drug interaction analysis are acquired during an episode of simulated high altitude (Cycle 1), at least 7 days past screening
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2015.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert J Noveck, MD, PhD principal investigator
Duke University
Claude A Piantadosi, MD study director
Duke University
Thies Schroeder, PhD study director
Duke University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Aminophylline 400 mg and Ambrisentan 5 mg in people with Acute Mountain Sickness and Fatigue, run by Robert J Noveck, M.D. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The safety of combined or single-dose aminophylline and ambrisentan at simulated high altitude in resting human subjects (time frame: Safety endpoints will be measured during an episode of simulated high altitude (Cycle 1), at least 7 days post screening). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2015.