RECRUITING

Advair HFA in Healthy and HAPE Predisposed Subjects

Conditions

Altitude Edema salmeterol fluticasone exercise performance high altitude pulmonary edema hypoxia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The current protocol is composed of two studies. The first study is designed to carefully evaluate the safety of high-dose salmeterol/fluticasone (Advair HFA) versus placebo (hydrofluoroalkane, HFA) administration over 7 days, as well as the efficacy of the study drug to increase exercise performance, in healthy individuals exercising under hypoxic, simulated high-altitude conditions (Phase 1/2a study). The second study will examine sensitive measures of cardiopulmonary function using invasive cardiopulmonary testing, in both HAPE-sensitive and HAPE-resistant individuals, to assess the potential efficacy of salmeterol/fluticasone to prevent pulmonary edema and to enhance exercise capacity (Phase 2a) in these individuals.

Official Title

Double-Blinded, Placebo-Controlled, Randomized, 2 Period, Crossover Phase 1/2a Study Testing Safety/Efficacy of Advair HFA (Salmeterol, Fluticasone) in Resting & Exercising Healthy & High Altitude Pulmonary Edema (HAPE) Predisposed Subjects

Quick Facts

Study Start:2023-12-12

Study Completion:2026-11-15

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06040268

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 50 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
* Written informed consent signed prior to entry into the study. * Male or female age 18-50 years of age * BMI ≥ 20 and \< 35 kg/m2 * Agreement to comply with the study-required interventions and treatment during the full duration of the study. * In good health as determined by screening medical history, physical examination, vital signs (blood pressure, heart rate, respiratory rate and temperature), clinical laboratory tests (CBC, protime (PT) (INR)/partial thromboplastin time (PTT), thyroid stimulating hormone (TSH), Total Bilirubin, blood chemistries, urine drug screening), and a resting 12-lead Electrocardiogram with a 10 second rhythm strip. * Adequate peripheral venous access for IV insertion and blood sample collection (assessments will be made prior to undergoing further assessments). * HAPE-susceptible individuals (Study 2 only) must have had a medically documented (hospital admission or emergency room visit) HAPE episode characterized by noncardiogenic pulmonary edema and hypoxemia that occurred during high altitude travel in Colorado and must reside below 3,000 feet (unacclimatized individuals; non-Colorado residents). * HAPE-resistant individuals (Study 2 only) will have had no evidence of HAPE during high altitude travel in Colorado, and must reside below 3,000 feet (unacclimatized; often being travel partners of HAPE-susceptible subjects). * Healthy controls (Study 1 only) will all be Colorado residents.	* Currently participating in or has been enrolled in another clinical trial within the last 30 days (observational studies are acceptable). * Donation of any blood or plasma in the last month, or donation of \> 500 milliliters (ml) of blood within the 3 months preceding study drug administration. * Female subjects of childbearing potential with positive serum pregnancy (beta human chorionic gonadotropin) test, who are breastfeeding, plan to become pregnant during the study, or decline to either be abstinent or use highly effective birth control if they have sexual intercourse with a male partner (ie, oral contraceptives; contraceptive patches, implants, injections, and rings; intrauterine devices - both hormonally-impregnated and untreated devices) throughout the study and for at least 1 month after study completion; * Known history of impaired liver function * Clinically significant laboratory abnormalities (one retest is allowed at the discretion of the Investigator and Medical Monitor), defined as: * Impaired renal function as estimated glomerular filtration rate \< 60 mL/min/1.73 m2) as estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening.(81) * Serum Potassium \< 3.2 millimolar (mM) * aspartate aminotransferase (AST) or alanine transaminase (ALT) \> 2x upper reference limit * international normalized ratio (INR) \> 1.5 * Fasting serum triglycerides \> 500 mg/dL (lipemic serum affects assays) * TSH \< 0.5 or \> 5 milliunits/Liter (mU/L) * Hemoglobin \< 12.0 g/dL * Bilirubin \> 2, unless consistent with Gilbert's disorder (indirect bilirubinemia) * Platelet count \< 100,000/µL * Any other abnormality deemed by the Investigator to exceed normal safety limits for this study or exclude subject participation. * Cardiovascular conditions: * Clinically significant abnormal electrocardiogram at screening: * Any history of congenital or acquired long QT syndrome * Any history of uncorrected re-entrant supraventricular tachycardia, atrial fibrillation, sinus tachycardia (\> 100 bpm at rest), or ventricular tachycardia. * Evidence of conduction abnormality including QTc prolongation on ECG, defined as \> 450 msec for men and \> 470 msec for women * Unstable angina pectoris, history of myocardial infarction (MI), transient ischemic attack (TIA) or stroke within 3 months prior to screening, or subjects who have ever undergone percutaneous coronary intervention or a coronary artery bypass or who are due to undergo these procedures at the time of screening, as evidence of atherosclerotic cardiovascular disease (ASCVD). * New York Heart Association Functional Class I-IV congestive heart failure (any congestive heart failure) * Use of any blood thinner (e.g. novel oral anticoagulant, coumadin/warfarin). Use of aspirin is acceptable for study and will not need to be discontinued prior to involvement in the study. Use of a P2Y12 inhibitor (such as clopidogrel) is also not permitted due to bleeding risks. * Use of any phosphodiesterase-5 inhibitors (as prescribed medications or obtained by other means) such as sildenafil, tadalafil, or vardenafil (as they may enhance hypoxic exercise performance) * Infectious conditions: * Concomitant Medications: * Nonselective beta-blockers including propranolol, carvedilol, and labetalol (due to antagonization of beta-2 agonist effects) * Use of any inhaled or oral beta-2 receptor agonists, or oral theophylline * Non-potassium sparing diuretics (due to hypokalemia risks) * The use of any medication known to be a strong inhibitor or strong inducer of cytochrome P (CYP) 3A4 or 3A5 enzymes (cytochrome P450 isoenzymes) that metabolize salmeterol.(66) Also, any medication that has been reported to have a major or moderate interaction with salmeterol or fluticasone(82) * Use of monoamine oxidase inhibitors or tricyclic antidepressants within 2 weeks of screening * Prescription amphetamines or other sympathetic stimulants used for disorders such as narcolepsy, somnolence, or attention deficit disorder * History of claustrophobia or post traumatic stress disorder that would limit use of gas breathing masks or mouthpieces. * Essential tremor limiting handwriting, or any tremor requiring medication.

Inclusion Criteria

Exclusion Criteria

* Written informed consent signed prior to entry into the study.
* Male or female age 18-50 years of age
* BMI ≥ 20 and \< 35 kg/m2
* Agreement to comply with the study-required interventions and treatment during the full duration of the study.
* In good health as determined by screening medical history, physical examination, vital signs (blood pressure, heart rate, respiratory rate and temperature), clinical laboratory tests (CBC, protime (PT) (INR)/partial thromboplastin time (PTT), thyroid stimulating hormone (TSH), Total Bilirubin, blood chemistries, urine drug screening), and a resting 12-lead Electrocardiogram with a 10 second rhythm strip.
* Adequate peripheral venous access for IV insertion and blood sample collection (assessments will be made prior to undergoing further assessments).
* HAPE-susceptible individuals (Study 2 only) must have had a medically documented (hospital admission or emergency room visit) HAPE episode characterized by noncardiogenic pulmonary edema and hypoxemia that occurred during high altitude travel in Colorado and must reside below 3,000 feet (unacclimatized individuals; non-Colorado residents).
* HAPE-resistant individuals (Study 2 only) will have had no evidence of HAPE during high altitude travel in Colorado, and must reside below 3,000 feet (unacclimatized; often being travel partners of HAPE-susceptible subjects).
* Healthy controls (Study 1 only) will all be Colorado residents.

* Currently participating in or has been enrolled in another clinical trial within the last 30 days (observational studies are acceptable).
* Donation of any blood or plasma in the last month, or donation of \> 500 milliliters (ml) of blood within the 3 months preceding study drug administration.
* Female subjects of childbearing potential with positive serum pregnancy (beta human chorionic gonadotropin) test, who are breastfeeding, plan to become pregnant during the study, or decline to either be abstinent or use highly effective birth control if they have sexual intercourse with a male partner (ie, oral contraceptives; contraceptive patches, implants, injections, and rings; intrauterine devices - both hormonally-impregnated and untreated devices) throughout the study and for at least 1 month after study completion;
* Known history of impaired liver function
* Clinically significant laboratory abnormalities (one retest is allowed at the discretion of the Investigator and Medical Monitor), defined as:
* Impaired renal function as estimated glomerular filtration rate \< 60 mL/min/1.73 m2) as estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening.(81)
* Serum Potassium \< 3.2 millimolar (mM)
* aspartate aminotransferase (AST) or alanine transaminase (ALT) \> 2x upper reference limit
* international normalized ratio (INR) \> 1.5
* Fasting serum triglycerides \> 500 mg/dL (lipemic serum affects assays)
* TSH \< 0.5 or \> 5 milliunits/Liter (mU/L)
* Hemoglobin \< 12.0 g/dL
* Bilirubin \> 2, unless consistent with Gilbert's disorder (indirect bilirubinemia)
* Platelet count \< 100,000/µL
* Any other abnormality deemed by the Investigator to exceed normal safety limits for this study or exclude subject participation.
* Cardiovascular conditions:
* Clinically significant abnormal electrocardiogram at screening:
* Any history of congenital or acquired long QT syndrome
* Any history of uncorrected re-entrant supraventricular tachycardia, atrial fibrillation, sinus tachycardia (\> 100 bpm at rest), or ventricular tachycardia.
* Evidence of conduction abnormality including QTc prolongation on ECG, defined as \> 450 msec for men and \> 470 msec for women
* Unstable angina pectoris, history of myocardial infarction (MI), transient ischemic attack (TIA) or stroke within 3 months prior to screening, or subjects who have ever undergone percutaneous coronary intervention or a coronary artery bypass or who are due to undergo these procedures at the time of screening, as evidence of atherosclerotic cardiovascular disease (ASCVD).
* New York Heart Association Functional Class I-IV congestive heart failure (any congestive heart failure)
* Use of any blood thinner (e.g. novel oral anticoagulant, coumadin/warfarin). Use of aspirin is acceptable for study and will not need to be discontinued prior to involvement in the study. Use of a P2Y12 inhibitor (such as clopidogrel) is also not permitted due to bleeding risks.
* Use of any phosphodiesterase-5 inhibitors (as prescribed medications or obtained by other means) such as sildenafil, tadalafil, or vardenafil (as they may enhance hypoxic exercise performance)
* Infectious conditions:
* Concomitant Medications:
* Nonselective beta-blockers including propranolol, carvedilol, and labetalol (due to antagonization of beta-2 agonist effects)
* Use of any inhaled or oral beta-2 receptor agonists, or oral theophylline
* Non-potassium sparing diuretics (due to hypokalemia risks)
* The use of any medication known to be a strong inhibitor or strong inducer of cytochrome P (CYP) 3A4 or 3A5 enzymes (cytochrome P450 isoenzymes) that metabolize salmeterol.(66) Also, any medication that has been reported to have a major or moderate interaction with salmeterol or fluticasone(82)
* Use of monoamine oxidase inhibitors or tricyclic antidepressants within 2 weeks of screening
* Prescription amphetamines or other sympathetic stimulants used for disorders such as narcolepsy, somnolence, or attention deficit disorder
* History of claustrophobia or post traumatic stress disorder that would limit use of gas breathing masks or mouthpieces.
* Essential tremor limiting handwriting, or any tremor requiring medication.

Contacts and Locations

Study Contact

James P Maloney, MD

CONTACT

3037246072

james.maloney@ucdenver.edu

Principal Investigator

James P Maloney, MD

PRINCIPAL_INVESTIGATOR

Univ. of Colorado, Denver

Study Locations (Sites)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045

United States

Collaborators and Investigators

Sponsor: University of Colorado, Denver

James P Maloney, MD, PRINCIPAL_INVESTIGATOR, Univ. of Colorado, Denver

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-12-12

Study Completion Date2026-11-15

Study Record Updates

Study Start Date2023-12-12

Study Completion Date2026-11-15

Terms related to this study

Keywords Provided by Researchers

salmeterol
fluticasone
exercise performance
high altitude pulmonary edema
hypoxia

Additional Relevant MeSH Terms

Altitude Edema