Exercise-induced Arterial HypoxemiaNCT04305873
Cytokine and Stress Hormone Responses to Exercise-induced Hypoxemia Among Endurance-trained
An observational study of Exercise-induced Arterial Hypoxemia, run by Gepner Yftach at 1 site in Israel.
Trial summary
It is well documented that exercise-induced arterial hypoxemia (EIAH) is highly prevalent among endurance-trained athletes performing heavy intensity exercise, regardless of sex and age. Although it has been shown that a drop in arterial oxyhemoglobin saturation (SaO2) during exercise (i.e. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Exercise-induced Arterial Hypoxemia
- How many people
- 50 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Mar 2020to 1 Sep 2024
- Phase
- Observational
- 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 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Highly endurance trained athletes who have run a half marathon or marathon in the past.
Who may be able to join
- 1) Physically active (minimum of 50 km running/week) and maximal oxygen consumption > 55 and 50 ml/kg-1/min-1 for men and women, respectively.
- 2) classified as low risk based on a medical questionnaire, body mass index and non-smoking status.
- 3) No history of pulmonary, metabolic and/or cardiovascular disease.
- 4) normal pulmonary function as defined by a ≥ 80% of predicted forced vital capacity (FVC), forced expired volume in one second (FEV1) and FEV1/FVC according the American Thoracic Society standards.
Who cannot join
- Smoking and/or any pulmonary, metabolic and/or cardiovascular disease.
- maximal oxygen consumption lower than set criteria.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Exercise-induced Hypoxemia on Cytokine and Stress Hormone Responses Among Endurance-trained Athletes
It is well documented that exercise-induced arterial hypoxemia (EIAH) is highly prevalent among endurance-trained athletes performing heavy intensity exercise, regardless of sex and age. Although it has been shown that a drop in arterial oxyhemoglobin saturation (SaO2) during exercise (i.e. EIAH) negatively affects aerobic capacity measures such as VO2max and time trial performance, there remains a gap in the literature as to the physiological consequences of EIAH, and specifically acute cytokines and stress-related responses to hypoxemia during exercise. Exposure to hypoxic environments in which SaO2 is reduced and exercise can each, independently, alter/activate various pro- and anti-inflammatory markers and increases stress hormones. It follows then that EIAH athletes could be more susceptible to, and encounter more frequently, episodes of elevated levels of inflammatory cytokines and an exaggerated stress response than non-EIAH athletes; however, to the best of the investigators knowledge, this is yet to be confirmed. Therefore, it is hypothesized that highly trained endurance athletes who develop EIAH will experience more pronounced increases in inflammatory cytokines and stress hormones following a bout of heavy intensity exercise compared to athletes without EIAH.
Read the detailed description
Fifty highly trained endurance runners (men and women, age: 18-35 years) will be recruited for this study. The first testing session will serve as a screening tool to determine subject eligibility. Following the first testing sessions subjects will be divided into EIAH or non-EIAH groups based on SaO2 at VO2max (EIAH < 93%, non-EIAH > 95%; Dempsey and Wagner criteria). Subjects with intermediate SaO2 (93-95% at VO2max) values will be included in the study for correlational analyses only.
All subjects will be advised orally, and in writing, as to the nature of the experiments and will give written, informed consent to the study protocol.
Study Design \& protocol:
Subjects will be asked to visit the Exercise Performance Laboratory at the Sylvan Adams Sports Institute on three occasions. During the first visit subject will perform resting pulmonary function tests (PFTs) followed by a graded exercise test to exhaustion on either a motorized-treadmill for the determination of VO2max, degree of EIAH (SaO2 at VO2max) and maximal heart rate (HRmax). On the second visit, subjects will perform PFTs, followed by a brief warm-up run for 10 min at a moderate intensity equivalent to 60% of HRmax, as obtained from the incremental test and a 30-min trial at either half-marathon pace (HM30), designed to simulate a tempo workout often practiced by endurance runners. The third visit, conducted 24 hours after the 30-min trial, will include a blood draw only.
- Conditions
- Exercise-induced Arterial Hypoxemia
- Keywords
- High intensity exercise, Endurance, Athletes, Desaturation, Stress response, Inflammatory markers
- Medical subject headings
- Fractures, Stress
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| EIAH athletes | Athletes with arterial oxyhemoglobin saturation at maximal exercise during a graded exercise test <93% | |
| Non-EIAH athletes | Athletes with arterial oxyhemoglobin saturation at maximal exercise during a graded exercise test >95% | |
| Intermediate EIAH athletes | Athletes with arterial oxyhemoglobin saturation at maximal exercise during a graded exercise test of 93-95% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inflammatory cytokines
Changes in Inflammatory cytokines (e.g. IL-6, IL-1b, IL-ra, IL-10)
Measured: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Inflammatory cytokine
Changes in Inflammatory cytokine TNF-a
Measured: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Changes in Cortisol level
Stress hormones
Measured: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Changes in epinephrine level
Stress hormones
Measured: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Changes in norepinephrine level
Stress hormones
Measured: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Secondary outcomes (4)
Changes in number of Neutrophiles
Measured: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Changes in number of lymphocytes
Measured: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Changes in number of monocytes
Measured: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Immune markers
Changes in basophiles count (number of)
Measured: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2020
- Study start1 Mar 2020
- Primary completion1 May 2024 (estimated)
- Study completion1 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Exercise-induced Arterial HypoxemiaStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gepner Yftach
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gepner Yftach, Tel Aviv University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04305873
- Sponsor's protocol ID
- EIAH1
- Status last verified
- Feb 2024
- First submitted
- 4 Mar 2020
- Last updated
- 22 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Babb TG. Exercise ventilatory limitation: the role of expiratory flow limitation. Exerc Sport Sci Rev. 2013 Jan;41(1):11-8. doi: 10.1097/JES.0b013e318267c0d2.
PubMed 23038244Bayliss DA, Millhorn DE. Central neural mechanisms of progesterone action: application to the respiratory system. J Appl Physiol (1985). 1992 Aug;73(2):393-404. doi: 10.1152/jappl.1992.73.2.393.
PubMed 1399957Beaver WL, Wasserman K, Whipp BJ. A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol (1985). 1986 Jun;60(6):2020-7. doi: 10.1152/jappl.1986.60.6.2020.
PubMed 3087938Behan M, Kinkead R. Neuronal control of breathing: sex and stress hormones. Compr Physiol. 2011 Oct;1(4):2101-39. doi: 10.1002/cphy.c100027.
PubMed 23733699Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377-81.
PubMed 7154893Chapman RF, Emery M, Stager JM. Extent of expiratory flow limitation influences the increase in maximal exercise ventilation in hypoxia. Respir Physiol. 1998 Jul;113(1):65-74. doi: 10.1016/s0034-5687(98)00043-7.
PubMed 9776552Duke JW, Stickford JL, Weavil JC, Chapman RF, Stager JM, Mickleborough TD. Operating lung volumes are affected by exercise mode but not trunk and hip angle during maximal exercise. Eur J Appl Physiol. 2014 Nov;114(11):2387-97. doi: 10.1007/s00421-014-2956-0. Epub 2014 Aug 2.
PubMed 25085604Pearman T, Yanez B, Peipert J, Wortman K, Beaumont J, Cella D. Ambulatory cancer and US general population reference values and cutoff scores for the functional assessment of cancer therapy. Cancer. 2014 Sep 15;120(18):2902-9. doi: 10.1002/cncr.28758. Epub 2014 May 22.
PubMed 24853866Johnson BD, Saupe KW, Dempsey JA. Mechanical constraints on exercise hyperpnea in endurance athletes. J Appl Physiol (1985). 1992 Sep;73(3):874-86. doi: 10.1152/jappl.1992.73.3.874.
PubMed 1400051Johnson BD, Weisman IM, Zeballos RJ, Beck KC. Emerging concepts in the evaluation of ventilatory limitation during exercise: the exercise tidal flow-volume loop. Chest. 1999 Aug;116(2):488-503. doi: 10.1378/chest.116.2.488.
PubMed 10453881McClaran SR, Harms CA, Pegelow DF, Dempsey JA. Smaller lungs in women affect exercise hyperpnea. J Appl Physiol (1985). 1998 Jun;84(6):1872-81. doi: 10.1152/jappl.1998.84.6.1872.
PubMed 9609779Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.
PubMed 16055882Weavil JC, Duke JW, Stickford JL, Stager JM, Chapman RF, Mickleborough TD. Endurance exercise performance in acute hypoxia is influenced by expiratory flow limitation. Eur J Appl Physiol. 2015 Aug;115(8):1653-63. doi: 10.1007/s00421-015-3145-5. Epub 2015 Mar 13.
PubMed 25761731Romer LM, Dempsey JA, Lovering A, Eldridge M. Exercise-induced arterial hypoxemia: consequences for locomotor muscle fatigue. Adv Exp Med Biol. 2006;588:47-55. doi: 10.1007/978-0-387-34817-9_5.
PubMed 17089878Amann M, Eldridge MW, Lovering AT, Stickland MK, Pegelow DF, Dempsey JA. Arterial oxygenation influences central motor output and exercise performance via effects on peripheral locomotor muscle fatigue in humans. J Physiol. 2006 Sep 15;575(Pt 3):937-52. doi: 10.1113/jphysiol.2006.113936. Epub 2006 Jun 22.
PubMed 16793898
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Exercise-induced Hypoxemia on Cytokine and Stress Hormone Responses Among Endurance-trained Athletes
- ClinicalTrials.gov ID
- NCT04305873
- Acronym / sponsor ID
- EIAH1
- Conditions
- Exercise-induced Arterial Hypoxemia
- Keywords
- High intensity exercise, Endurance, Athletes, Desaturation, Stress response, Inflammatory markers
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Gepner YftachUniversity, hospital or other
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 1 May 2024 (estimated)
- Study completion
- 1 Sep 2024 (estimated)
- First posted
- 12 Mar 2020 (actual)
- 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.
It is well documented that exercise-induced arterial hypoxemia (EIAH) is highly prevalent among endurance-trained athletes performing heavy intensity exercise, regardless of sex and age. Although it has been shown that a drop in arterial oxyhemoglobin saturation (SaO2) during exercise (i.e. EIAH) negatively affects aerobic capacity measures such as VO2max and time trial performance, there remains a gap in the literature as to the physiological consequences of EIAH, and specifically acute cytokines and stress-related responses to hypoxemia during exercise. Exposure to hypoxic environments in which SaO2 is reduced and exercise can each, independently, alter/activate various pro- and anti-inflammatory markers and increases stress hormones. It follows then that EIAH athletes could be more susceptible to, and encounter more frequently, episodes of elevated levels of inflammatory cytokines and an exaggerated stress response than non-EIAH athletes; however, to the best of the investigators knowledge, this is yet to be confirmed. Therefore, it is hypothesized that highly trained endurance athletes who develop EIAH will experience more pronounced increases in inflammatory cytokines and stress hormones following a bout of heavy intensity exercise compared to athletes without EIAH.
Detailed description
Fifty highly trained endurance runners (men and women, age: 18-35 years) will be recruited for this study. The first testing session will serve as a screening tool to determine subject eligibility. Following the first testing sessions subjects will be divided into EIAH or non-EIAH groups based on SaO2 at VO2max (EIAH < 93%, non-EIAH > 95%; Dempsey and Wagner criteria). Subjects with intermediate SaO2 (93-95% at VO2max) values will be included in the study for correlational analyses only.
All subjects will be advised orally, and in writing, as to the nature of the experiments and will give written, informed consent to the study protocol.
Study Design \& protocol:
Subjects will be asked to visit the Exercise Performance Laboratory at the Sylvan Adams Sports Institute on three occasions. During the first visit subject will perform resting pulmonary function tests (PFTs) followed by a graded exercise test to exhaustion on either a motorized-treadmill for the determination of VO2max, degree of EIAH (SaO2 at VO2max) and maximal heart rate (HRmax). On the second visit, subjects will perform PFTs, followed by a brief warm-up run for 10 min at a moderate intensity equivalent to 60% of HRmax, as obtained from the incremental test and a 30-min trial at either half-marathon pace (HM30), designed to simulate a tempo workout often practiced by endurance runners. The third visit, conducted 24 hours after the 30-min trial, will include a blood draw only.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| EIAH athletes | – | –Athletes with arterial oxyhemoglobin saturation at maximal exercise during a graded exercise test <93% |
| Non-EIAH athletes | – | –Athletes with arterial oxyhemoglobin saturation at maximal exercise during a graded exercise test >95% |
| Intermediate EIAH athletes | – | –Athletes with arterial oxyhemoglobin saturation at maximal exercise during a graded exercise test of 93-95% |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Highly endurance trained athletes who have run a half marathon or marathon in the past.
Key inclusion criteria (4 listed)
- 1) Physically active (minimum of 50 km running/week) and maximal oxygen consumption > 55 and 50 ml/kg-1/min-1 for men and women, respectively.
- 2) classified as low risk based on a medical questionnaire, body mass index and non-smoking status.
- 3) No history of pulmonary, metabolic and/or cardiovascular disease.
- 4) normal pulmonary function as defined by a ≥ 80% of predicted forced vital capacity (FVC), forced expired volume in one second (FEV1) and FEV1/FVC according the American Thoracic Society standards.
Key exclusion criteria (2 listed)
- Smoking and/or any pulmonary, metabolic and/or cardiovascular disease.
- maximal oxygen consumption lower than set criteria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Inflammatory cytokines
Time frame: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Changes in Inflammatory cytokines (e.g. IL-6, IL-1b, IL-ra, IL-10)
Inflammatory cytokine
Time frame: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Changes in Inflammatory cytokine TNF-a
Changes in Cortisol level
Time frame: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Stress hormones
Changes in epinephrine level
Time frame: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Stress hormones
Changes in norepinephrine level
Time frame: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Stress hormones
4 secondary outcomes
Changes in number of Neutrophiles
Time frame: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Changes in number of lymphocytes
Time frame: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Changes in number of monocytes
Time frame: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Immune markers
Time frame: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2024.
- Background: PubMed 23038244Babb TG. Exercise ventilatory limitation: the role of expiratory flow limitation. Exerc Sport Sci Rev. 2013 Jan;41(1):11-8. doi: 10.1097/JES.0b013e318267c0d2.
- Background: PubMed 1399957Bayliss DA, Millhorn DE. Central neural mechanisms of progesterone action: application to the respiratory system. J Appl Physiol (1985). 1992 Aug;73(2):393-404. doi: 10.1152/jappl.1992.73.2.393.
- Background: PubMed 3087938Beaver WL, Wasserman K, Whipp BJ. A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol (1985). 1986 Jun;60(6):2020-7. doi: 10.1152/jappl.1986.60.6.2020.
- Background: PubMed 23733699Behan M, Kinkead R. Neuronal control of breathing: sex and stress hormones. Compr Physiol. 2011 Oct;1(4):2101-39. doi: 10.1002/cphy.c100027.
- Background: PubMed 7154893Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377-81.
- Background: PubMed 9776552Chapman RF, Emery M, Stager JM. Extent of expiratory flow limitation influences the increase in maximal exercise ventilation in hypoxia. Respir Physiol. 1998 Jul;113(1):65-74. doi: 10.1016/s0034-5687(98)00043-7.
- Background: PubMed 25085604Duke JW, Stickford JL, Weavil JC, Chapman RF, Stager JM, Mickleborough TD. Operating lung volumes are affected by exercise mode but not trunk and hip angle during maximal exercise. Eur J Appl Physiol. 2014 Nov;114(11):2387-97. doi: 10.1007/s00421-014-2956-0. Epub 2014 Aug 2.
- Background: PubMed 24853866Pearman T, Yanez B, Peipert J, Wortman K, Beaumont J, Cella D. Ambulatory cancer and US general population reference values and cutoff scores for the functional assessment of cancer therapy. Cancer. 2014 Sep 15;120(18):2902-9. doi: 10.1002/cncr.28758. Epub 2014 May 22.
- Background: PubMed 1400051Johnson BD, Saupe KW, Dempsey JA. Mechanical constraints on exercise hyperpnea in endurance athletes. J Appl Physiol (1985). 1992 Sep;73(3):874-86. doi: 10.1152/jappl.1992.73.3.874.
- Background: PubMed 10453881Johnson BD, Weisman IM, Zeballos RJ, Beck KC. Emerging concepts in the evaluation of ventilatory limitation during exercise: the exercise tidal flow-volume loop. Chest. 1999 Aug;116(2):488-503. doi: 10.1378/chest.116.2.488.
- Background: PubMed 9609779McClaran SR, Harms CA, Pegelow DF, Dempsey JA. Smaller lungs in women affect exercise hyperpnea. J Appl Physiol (1985). 1998 Jun;84(6):1872-81. doi: 10.1152/jappl.1998.84.6.1872.
- Background: PubMed 16055882Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Exercise-induced Arterial Hypoxemia, run by Gepner Yftach at 1 site in Israel.
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 4 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
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?
Inflammatory cytokines (time frame: Changes from baseline to immediately, 2 hour and 24 hour post 30 minutes run at half marathon pace (HM30)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04305873, which also lists 22 linked publications.
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 22 Feb 2024.