Impaired Oxygen DeliveryNCT01454128
The Role of Exercise-Periodic-Breathing (EPB) in Impaired Ventilation Regulation Dysfunction in Heart Failure Patients
A study testing exercise in people with Impaired Oxygen Delivery and Ischemic Reperfusion Injury, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial summary
Heart failure (HF) is a complex syndrome characterized by myocardial dysfunction and an impaired regulatory function of multiple organ systems which were resulted from impaired cardiac output and consequently impaired perfusion of target organ. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Impaired Oxygen Delivery, Ischemic Reperfusion Injury
- What is being tested?
- exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 1 siteTaiwan
- Study dates
- Apr 2011to Mar 2013
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- cardiac event with optimal medial treatment within 3 months and have 4 more weeks spared from heart disease attack or major cardiac procedure.
Who cannot join
- unstable angina pectoris
- uncompensated heart failure
- myocardial infarction during the past 4 weeks
- complex ventricular arrhythmias
- orthopedic or neurological limitations to exercise
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Dept of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital
Keelung, 204
About this study
Official title: The Role of Exercise-Periodic-Breathing in Impaired Ventilation Regulation Dysfunction in Patients With Heart Failure
Heart failure (HF) is a complex syndrome characterized by myocardial dysfunction and an impaired regulatory function of multiple organ systems which were resulted from impaired cardiac output and consequently impaired perfusion of target organ. In cardiopulmonary exercise test (CPET), the investigators found there is periodic oscillation in minute ventilation of some patient. With periodic breathing (PB), clear oscillations in oxygen uptake, carbon dioxide output, tidal volume and left ventricle ejection fraction (LVEF) were also noted. Exertional hyper-ventilation that is caused by HF may further induce vasoconstriction during exercise and lead to further dysfunction of end-organ and muscle. Reduced end-organ perfusion/oxygenation may critically limit exercise performance. Hypoxic change during nadir phase of PB may deteriorate the exercise limitation. Physical training can have beneficial effects which can effectively counteract the progression of deleterious compensatory mechanisms of HF. Whether exercise yields the same beneficial effect on ventilation oscillation and inefficacy is not clear.
The investigators will observe the real-time cardiac and hemodynamic change respond to exercise with periodic breathing change. The investigators expect that these results obtained from this study can aid in determining appropriate exercise intervention to improve aerobic fitness as well as simultaneously improve hemodynamic control in patients with HF. A quasi-experimental design will be used in this investigation. 60 HF patients will be recruited from Chang Gung Medical Foundation, Keelung Branch after they have provided informed consent. These subjects will be divided into PB (n=30) and non-PB groups (n=30) by their expression of CPET. Patients from each groups received the same therapy and trace course for 2years including CV clinics, CPET and polysomnography. The investigators will measure subjects' physical fitness, oxygen transport and utilization of exercising skeletal muscles, cardiovascular functions and hemodynamics, blood cell parameters, RBC deformity and aggregation, plasma biomarkers of myocardial damage, oxygen stress and quality of life at pre-training stage and following the 6th , 12th, 18th, 24th months of the tracing program. Experimental results were analyzed by descriptive statistics, independent t-test, and repeated measure ANOVA. The investigators study the above parameter to realize the physiological response to exercise of these patients and discover the appropriate exercise intensity for prescription for EPB.
Read the detailed description
Patients with heart failure display dyspnea on exertion, lower PCO2 and higher ventilatory response to exercise (V E -V CO 2slope), which demonstrated dysregulation of breathing in this disease category. Some of these patients develop further ventilation dysregulation pattern with ventilatory oscillation composed with exercise periodic breathing (EPB) and sleep apnea. Previous studies revealed the ventilatory oscillation was associated with cyclic changes in arterial oxygen (PO2) and carbon dioxide (PCO2) tensions, and also associated with severely impaired exercise tolerance, a steep V E -V CO 2slope, and low peak O 2 consumption, both correlated with the worse severity of heart failure and adverse prognosis. The origin of ventilatory oscillation might involved instability of the ventilator control system, which composed with prolonged circulatory delay, abnormal peripheral ergoreflex activation and peripheral chemo- and baro-sensitivity, even through abnormal autonomic reflexes to an altered central command. However, the most studies investigated these responses via sleep apnea under resting status especially those about brain. The real-time change response to exercise was limited to ventilatory parameters such as oxygen consumption, carbon dioxide production. Whether the exercise periodic breathing response to exercise which lead to abnormal cerebral hemodynamic responses to exercise in HF remain unclear.
Impaired cerebral blood flow was demonstrated during apnetic episode and related to neuropsychological deficits in sleep apnea patient. To be controlled by the same key feedback mechanism, impaired cerebral blood flow during exercise in EPB patients could be speculated. Moreover, Cerebral hypo-perfusion responses to exercise may contribute to the impairment of functional capacity in patients with HF. Accordingly, we hypothesize that the abnormal cerebral hemodynamics by exercise periodic breathing during exercise is associated with the decline of functional capacity in patients with HF. Besides, Physical training can have beneficial effects which can effectively counteract the progression of deleterious compensatory mechanisms of HF. Whether exercise yields the same beneficial effect on ventilation oscillation and inefficacy is not clear.
We will observe the real-time cardiac and hemodynamic change respond to exercise with periodic breathing change. We expect that these results obtained from this study can aid in determining appropriate exercise intervention to improve aerobic fitness as well as simultaneously improve hemodynamic control in patients with HF. A quasi-experimental design will be used in this investigation. Sixty HF patients will be recruited from Chang Gung Medical Foundation, Keelung Branch after they have provided informed consent. These subjects will be divided into PB (n=30) and non-PB groups (n=30) by their expression of CPET. Patients from each groups received the same therapy and trace course for 2years including CV clinics, CPET and polysomnography. We will measure subjects' physical fitness, oxygen transport and utilization of exercising skeletal muscles, cardiovascular functions and hemodynamics, blood cell parameters, RBC deformity and aggregation, plasma biomarkers of myocardial damage, oxygen stress and quality of life at pre-training stage and following the 6th , 12th, 18th, 24th months of the tracing program. Experimental results were analyzed by descriptive statistics (percentage, mean, and standard deviation), independent t-test, and repeated measure ANOVA. We study the above parameter to realize the physiological response to exercise of these patients and discover the appropriate exercise intensity for prescription for EPB.
This study employed simultaneously a noninvasive, bio-reactance device (i.e., noninvasive continuous CO monitoring system, NICOM) to assess cardiac hemodynamics, and a near-infrared spectroscopy (NIRS) to monitor changes in cerebral and muscular perfusion/oxygenation. We further elucidated the real-time adaption between ventilator parameter and hemodynamic ones during ventilation oscillation in patients with HF.
- Being tested
- exercise
- Keywords
- exercise base rehabilitation, heart failure, periodic breathing, aerobic fitness
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
exerciseBehavioural
Also called cardiac rehabilitation
36 session supervised exercise intervention
| Study group | Role | What they receive |
|---|---|---|
| Non-EPB | Active comparator | with exercise Receives: Behavioral: exercise |
| EPB with exercise | Experimental | with exercise Receives: Behavioral: exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
VO2 max(maximal oxygen consumption)
During cardiopulmonary exercise test, we could measure the value of patients' maximal oxygen consumption. It could represent the functional level of heart failure patient and be the mortality prediction.
Measured: 2 years
Secondary outcomes (2)
EPB pattern
We define the exercise periodic breathing pattern in primary cardiopulmonary exercise test(CPET). After exercise intervention, we analyze the ventilation picture again in follow up CPET. (EPB also a morality prediction )
Measured: 2 years
All-cause mortality/CV morbidity
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2011 (estimated)
- Study startApr 2011
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Impaired Oxygen DeliveryStudies of the same condition, open and under way.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 600 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tieh-Cheng Fu, M.D, Principal investigator, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01454128
- Sponsor's protocol ID
- 99-2546B
- Status last verified
- May 2019
- First submitted
- 14 Oct 2011
- Last updated
- 21 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Corra U, Pistono M, Mezzani A, Braghiroli A, Giordano A, Lanfranchi P, Bosimini E, Gnemmi M, Giannuzzi P. Sleep and exertional periodic breathing in chronic heart failure: prognostic importance and interdependence. Circulation. 2006 Jan 3;113(1):44-50. doi: 10.1161/CIRCULATIONAHA.105.543173. Epub 2005 Dec 27.
PubMed 16380551Bradley TD, Logan AG, Kimoff RJ, Series F, Morrison D, Ferguson K, Belenkie I, Pfeifer M, Fleetham J, Hanly P, Smilovitch M, Tomlinson G, Floras JS; CANPAP Investigators. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med. 2005 Nov 10;353(19):2025-33. doi: 10.1056/NEJMoa051001.
PubMed 16282177Francis DP, Davies LC, Piepoli M, Rauchhaus M, Ponikowski P, Coats AJ. Origin of oscillatory kinetics of respiratory gas exchange in chronic heart failure. Circulation. 1999 Sep 7;100(10):1065-70. doi: 10.1161/01.cir.100.10.1065.
PubMed 10477531Leite JJ, Mansur AJ, de Freitas HF, Chizola PR, Bocchi EA, Terra-Filho M, Neder JA, Lorenzi-Filho G. Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation. J Am Coll Cardiol. 2003 Jun 18;41(12):2175-81. doi: 10.1016/s0735-1097(03)00460-1.
PubMed 12821243Yajima T, Koike A, Sugimoto K, Miyahara Y, Marumo F, Hiroe M. Mechanism of periodic breathing in patients with cardiovascular disease. Chest. 1994 Jul;106(1):142-6. doi: 10.1378/chest.106.1.142.
PubMed 8020261
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Exercise-Periodic-Breathing in Impaired Ventilation Regulation Dysfunction in Patients With Heart Failure
- ClinicalTrials.gov ID
- NCT01454128
- Acronym / sponsor ID
- 99-2546B
- Keywords
- exercise base rehabilitation, heart failure, periodic breathing, aerobic fitness
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 600 participants (actual)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 18 Oct 2011 (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.
Heart failure (HF) is a complex syndrome characterized by myocardial dysfunction and an impaired regulatory function of multiple organ systems which were resulted from impaired cardiac output and consequently impaired perfusion of target organ. In cardiopulmonary exercise test (CPET), the investigators found there is periodic oscillation in minute ventilation of some patient. With periodic breathing (PB), clear oscillations in oxygen uptake, carbon dioxide output, tidal volume and left ventricle ejection fraction (LVEF) were also noted. Exertional hyper-ventilation that is caused by HF may further induce vasoconstriction during exercise and lead to further dysfunction of end-organ and muscle. Reduced end-organ perfusion/oxygenation may critically limit exercise performance. Hypoxic change during nadir phase of PB may deteriorate the exercise limitation. Physical training can have beneficial effects which can effectively counteract the progression of deleterious compensatory mechanisms of HF. Whether exercise yields the same beneficial effect on ventilation oscillation and inefficacy is not clear.
The investigators will observe the real-time cardiac and hemodynamic change respond to exercise with periodic breathing change. The investigators expect that these results obtained from this study can aid in determining appropriate exercise intervention to improve aerobic fitness as well as simultaneously improve hemodynamic control in patients with HF. A quasi-experimental design will be used in this investigation. 60 HF patients will be recruited from Chang Gung Medical Foundation, Keelung Branch after they have provided informed consent. These subjects will be divided into PB (n=30) and non-PB groups (n=30) by their expression of CPET. Patients from each groups received the same therapy and trace course for 2years including CV clinics, CPET and polysomnography. The investigators will measure subjects' physical fitness, oxygen transport and utilization of exercising skeletal muscles, cardiovascular functions and hemodynamics, blood cell parameters, RBC deformity and aggregation, plasma biomarkers of myocardial damage, oxygen stress and quality of life at pre-training stage and following the 6th , 12th, 18th, 24th months of the tracing program. Experimental results were analyzed by descriptive statistics, independent t-test, and repeated measure ANOVA. The investigators study the above parameter to realize the physiological response to exercise of these patients and discover the appropriate exercise intensity for prescription for EPB.
Detailed description
Patients with heart failure display dyspnea on exertion, lower PCO2 and higher ventilatory response to exercise (V E -V CO 2slope), which demonstrated dysregulation of breathing in this disease category. Some of these patients develop further ventilation dysregulation pattern with ventilatory oscillation composed with exercise periodic breathing (EPB) and sleep apnea. Previous studies revealed the ventilatory oscillation was associated with cyclic changes in arterial oxygen (PO2) and carbon dioxide (PCO2) tensions, and also associated with severely impaired exercise tolerance, a steep V E -V CO 2slope, and low peak O 2 consumption, both correlated with the worse severity of heart failure and adverse prognosis. The origin of ventilatory oscillation might involved instability of the ventilator control system, which composed with prolonged circulatory delay, abnormal peripheral ergoreflex activation and peripheral chemo- and baro-sensitivity, even through abnormal autonomic reflexes to an altered central command. However, the most studies investigated these responses via sleep apnea under resting status especially those about brain. The real-time change response to exercise was limited to ventilatory parameters such as oxygen consumption, carbon dioxide production. Whether the exercise periodic breathing response to exercise which lead to abnormal cerebral hemodynamic responses to exercise in HF remain unclear.
Impaired cerebral blood flow was demonstrated during apnetic episode and related to neuropsychological deficits in sleep apnea patient. To be controlled by the same key feedback mechanism, impaired cerebral blood flow during exercise in EPB patients could be speculated. Moreover, Cerebral hypo-perfusion responses to exercise may contribute to the impairment of functional capacity in patients with HF. Accordingly, we hypothesize that the abnormal cerebral hemodynamics by exercise periodic breathing during exercise is associated with the decline of functional capacity in patients with HF. Besides, Physical training can have beneficial effects which can effectively counteract the progression of deleterious compensatory mechanisms of HF. Whether exercise yields the same beneficial effect on ventilation oscillation and inefficacy is not clear.
We will observe the real-time cardiac and hemodynamic change respond to exercise with periodic breathing change. We expect that these results obtained from this study can aid in determining appropriate exercise intervention to improve aerobic fitness as well as simultaneously improve hemodynamic control in patients with HF. A quasi-experimental design will be used in this investigation. Sixty HF patients will be recruited from Chang Gung Medical Foundation, Keelung Branch after they have provided informed consent. These subjects will be divided into PB (n=30) and non-PB groups (n=30) by their expression of CPET. Patients from each groups received the same therapy and trace course for 2years including CV clinics, CPET and polysomnography. We will measure subjects' physical fitness, oxygen transport and utilization of exercising skeletal muscles, cardiovascular functions and hemodynamics, blood cell parameters, RBC deformity and aggregation, plasma biomarkers of myocardial damage, oxygen stress and quality of life at pre-training stage and following the 6th , 12th, 18th, 24th months of the tracing program. Experimental results were analyzed by descriptive statistics (percentage, mean, and standard deviation), independent t-test, and repeated measure ANOVA. We study the above parameter to realize the physiological response to exercise of these patients and discover the appropriate exercise intensity for prescription for EPB.
This study employed simultaneously a noninvasive, bio-reactance device (i.e., noninvasive continuous CO monitoring system, NICOM) to assess cardiac hemodynamics, and a near-infrared spectroscopy (NIRS) to monitor changes in cerebral and muscular perfusion/oxygenation. We further elucidated the real-time adaption between ventilator parameter and hemodynamic ones during ventilation oscillation in patients with HF.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-EPB | Active comparator | Behavioral: exercisewith exercise |
| EPB with exercise | Experimental | Behavioral: exercisewith exercise |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- cardiac event with optimal medial treatment within 3 months and have 4 more weeks spared from heart disease attack or major cardiac procedure.
Key exclusion criteria (5 listed)
- unstable angina pectoris
- uncompensated heart failure
- myocardial infarction during the past 4 weeks
- complex ventricular arrhythmias
- orthopedic or neurological limitations to exercise
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 |
|---|---|---|
| exerciseAlso: cardiac rehabilitation36 session supervised exercise intervention | Behavioural | EPB with exercise, Non-EPB |
Primary outcome
VO2 max(maximal oxygen consumption)
Time frame: 2 years
During cardiopulmonary exercise test, we could measure the value of patients' maximal oxygen consumption. It could represent the functional level of heart failure patient and be the mortality prediction.
2 secondary outcomes
EPB pattern
Time frame: 2 years
All-cause mortality/CV morbidity
Time frame: 2 years
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 21 May 2019.
- Background: PubMed 16380551Corra U, Pistono M, Mezzani A, Braghiroli A, Giordano A, Lanfranchi P, Bosimini E, Gnemmi M, Giannuzzi P. Sleep and exertional periodic breathing in chronic heart failure: prognostic importance and interdependence. Circulation. 2006 Jan 3;113(1):44-50. doi: 10.1161/CIRCULATIONAHA.105.543173. Epub 2005 Dec 27.
- Background: PubMed 16282177Bradley TD, Logan AG, Kimoff RJ, Series F, Morrison D, Ferguson K, Belenkie I, Pfeifer M, Fleetham J, Hanly P, Smilovitch M, Tomlinson G, Floras JS; CANPAP Investigators. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med. 2005 Nov 10;353(19):2025-33. doi: 10.1056/NEJMoa051001.
- Background: PubMed 10477531Francis DP, Davies LC, Piepoli M, Rauchhaus M, Ponikowski P, Coats AJ. Origin of oscillatory kinetics of respiratory gas exchange in chronic heart failure. Circulation. 1999 Sep 7;100(10):1065-70. doi: 10.1161/01.cir.100.10.1065.
- Background: PubMed 12821243Leite JJ, Mansur AJ, de Freitas HF, Chizola PR, Bocchi EA, Terra-Filho M, Neder JA, Lorenzi-Filho G. Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation. J Am Coll Cardiol. 2003 Jun 18;41(12):2175-81. doi: 10.1016/s0735-1097(03)00460-1.
- Background: PubMed 8020261Yajima T, Koike A, Sugimoto K, Miyahara Y, Marumo F, Hiroe M. Mechanism of periodic breathing in patients with cardiovascular disease. Chest. 1994 Jul;106(1):142-6. doi: 10.1378/chest.106.1.142.
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.
Tieh-Cheng Fu, M.D principal investigator
Chang Gung Memorial Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing exercise in people with Impaired Oxygen Delivery and Ischemic Reperfusion Injury, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
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 1 inclusion and 5 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 21 May 2019. 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 Taiwan. 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?
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?
VO2 max(maximal oxygen consumption) (time frame: 2 years). 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 NCT01454128, which also lists 5 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 21 May 2019.