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Periodic BreathingNCT03532412

Different Loop Gain Phenotypes in Patients With Chronic Systolic Heart Failure and Periodic Breathing

An observational study of Periodic Breathing, run by Wissenschaftliches Institut Bethanien e.V at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Central sleep apnoea (CSA) is common in patients with chronic systolic heart failure (HFrEF). Various trials have shown a prevalence of 21 - 37% in this group of people. Up to 66% of patients with CSA and HFrEF present with periodic breathing (PB), which is considered being a marker of HF severity and poor prognosis. Read more about this study

Who is it for?
Any age
Conditions the study is for
Periodic Breathing
How many people
12 participants
Where
1 siteGermany
Study dates
28 Jun 2016to 14 Nov 2016
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Study population: Patients admitted to the sleep lab for diagnostic polysomnography.

Who may be able to join

  • Systolic heart failure with left-ventricular ejection fraction <45%
  • Apnea-Hypopnea index >15 per hour as determined by diagnostic polysomnography
  • Predominant central sleep apnea as defined by >50% central respiratory events

Who cannot join

  • <50 evaluable respiratory events for loop gain analysis during diagnostic polysomnography

Trial locations and contacts

1 site in 1 country.

Germany1 site
  • Wissenschaftliches Institut Bethanien für Pneumologie e.V.

    Solingen, 42699

Other trials in Germany

About this study

Central sleep apnoea (CSA) is common in patients with chronic systolic heart failure (HFrEF). Various trials have shown a prevalence of 21 - 37% in this group of people. Up to 66% of patients with CSA and HFrEF present with periodic breathing (PB), which is considered being a marker of HF severity and poor prognosis. Brack et al. summarized data from cohorts, longitudinal studies and retrospective analyses showing an independently increased risk of death in HF patients with PB (HR 2.1-5.7 in five of seven studies). Furthermore, PB in HF patients is known to reduce quality of life and exercise performance and to increase sympathetic nerve activity as well as the probability of malignant cardiac arrhythmias.

The pathogenesis of PB is characterized by an instability of ventilatory drive. The level of carbon dioxide (CO2) in blood and cerebrospinal fluid correlates linearly with minute ventilation. A high level of CO2 increases ventilation while hypocapnia dampens it. This control theory is based on the loop gain (LG), which represents the sensitivity and reactivity of the ventilatory system and comprises three components: The plant gain defines the capacity of the system to change PaCO2 in response to a change in ventilation (metabolic response). It is influenced by the lung volume as well as the anatomy of the thorax and the upper airways. The feedback gain is defined by the chemoreceptor responsiveness in reaction to blood gas changes. The controller gain is represented by the respiratory control center in the brain stem and defines the capacity of the system to change ventilation in response to a change in PaCO2 (ventilatory response).

Read more

Sands et al. proposed and validated a mathematical model based on the ventilatory cycle pattern that quantifies the feedback loop. The ratio of ventilatory and cycle duration within the PB pattern is defined as the duty ratio (DR), which is the basis to calculate the LG. Any temporary breathing disturbance causing a PB pattern with a LG < 1 stabilizes within a few breathing cycles. A LG > 1 represents an unstable ventilatory response and slight changes of CO2 are accompanied by overshooting and undershooting of the ventilation. In that case, the polysomnography shows the typical pattern of waxing and waning of the tidal volume and effort.

HF patients typically present with an increased LG due to an impaired left ventricular function and a hyperstimulation of pulmonary vagal receptors. Furthermore, Khoo showed an increased chemosensitivity (controller gain) as well as a decreased ventilatory capacity (plant gain) in this group of people.

Sands and colleagues characterized PB considering the mean LG derived from several ventilatory cycles during non-REM sleep. This retrospective study of PB in HFrEF patients addresses the following questions:

  1. Is a single LG value appropriate to characterize the individual PB?
  2. Does the LG depend on sleep stage and body position?
  3. Does the intraindividual LG variability allow for the discrimination of different PB phenotypes and, if so, do these phenotypes differ in further characteristics?
Keywords
Polysomnography, Sleep apnea, Central sleep apnea
Medical subject headings
Sleep Apnea Syndromes, Sleep Apnea, Central

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03532412
Study groupRoleWhat they receive
HF+CSA+PBSystolic heart failure with predominant central sleep apnea and periodic breathing

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Loop Gain

    Mathematically determined loop gain of periodic breathing according to Sands et al. [10] based on diagnostic polysomnography

    Measured: During one day of diagnostic polysomnography

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2018
  2. Study start28 Jun 2016
  3. Primary completion14 Nov 2016
  4. Study completion14 Nov 2016

Resources

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
Retrospective
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03532412
Sponsor's protocol ID
WI_LoopGain
Status last verified
Dec 2023
First submitted
9 May 2018
Last updated
15 Dec 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Brack T, Randerath W, Bloch KE. Cheyne-Stokes respiration in patients with heart failure: prevalence, causes, consequences and treatments. Respiration. 2012;83(2):165-76. doi: 10.1159/000331457. Epub 2011 Oct 18.

    PubMed 22025128
  • Javaheri S, Shukla R, Zeigler H, Wexler L. Central sleep apnea, right ventricular dysfunction, and low diastolic blood pressure are predictors of mortality in systolic heart failure. J Am Coll Cardiol. 2007 May 22;49(20):2028-34. doi: 10.1016/j.jacc.2007.01.084. Epub 2007 May 4.

    PubMed 17512359
  • Naughton MT. Epidemiology of central sleep apnoea in heart failure. Int J Cardiol. 2016 Mar;206 Suppl:S4-7. doi: 10.1016/j.ijcard.2016.02.125. Epub 2016 Feb 26.

    PubMed 26948168
  • Randerath W, Verbraecken J, Andreas S, Arzt M, Bloch KE, Brack T, Buyse B, De Backer W, Eckert DJ, Grote L, Hagmeyer L, Hedner J, Jennum P, La Rovere MT, Miltz C, McNicholas WT, Montserrat J, Naughton M, Pepin JL, Pevernagie D, Sanner B, Testelmans D, Tonia T, Vrijsen B, Wijkstra P, Levy P. Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep. Eur Respir J. 2017 Jan 18;49(1):1600959. doi: 10.1183/13993003.00959-2016. Print 2017 Jan.

    PubMed 27920092
  • Yumino D, Bradley TD. Central sleep apnea and Cheyne-Stokes respiration. Proc Am Thorac Soc. 2008 Feb 15;5(2):226-36. doi: 10.1513/pats.200708-129MG.

    PubMed 18250216
  • Kasai T, Floras JS, Bradley TD. Sleep apnea and cardiovascular disease: a bidirectional relationship. Circulation. 2012 Sep 18;126(12):1495-510. doi: 10.1161/CIRCULATIONAHA.111.070813. No abstract available.

    PubMed 22988046
  • Rowley JA, Badr MS. Central Sleep Apnea in Patients with Congestive Heart Failure. Sleep Med Clin. 2017 Jun;12(2):221-227. doi: 10.1016/j.jsmc.2017.03.001.

    PubMed 28477776
  • Naughton MT. Loop gain in apnea: gaining control or controlling the gain? Am J Respir Crit Care Med. 2010 Jan 15;181(2):103-5. doi: 10.1164/rccm.200909-1449ED. No abstract available.

    PubMed 20053968
  • Wellman A, Malhotra A, Fogel RB, Edwards JK, Schory K, White DP. Respiratory system loop gain in normal men and women measured with proportional-assist ventilation. J Appl Physiol (1985). 2003 Jan;94(1):205-12. doi: 10.1152/japplphysiol.00585.2002. Epub 2002 Sep 20.

    PubMed 12391042
  • Sands SA, Edwards BA, Kee K, Turton A, Skuza EM, Roebuck T, O'Driscoll DM, Hamilton GS, Naughton MT, Berger PJ. Loop gain as a means to predict a positive airway pressure suppression of Cheyne-Stokes respiration in patients with heart failure. Am J Respir Crit Care Med. 2011 Nov 1;184(9):1067-75. doi: 10.1164/rccm.201103-0577OC.

    PubMed 21816941
  • Khoo VS. MRI--"magic radiotherapy imaging" for treatment planning? Br J Radiol. 2000 Mar;73(867):229-33. doi: 10.1259/bjr.73.867.10817036. No abstract available.

    PubMed 10817036

Questions about this trial

What is this clinical trial studying?

An observational study of Periodic Breathing, run by Wissenschaftliches Institut Bethanien e.V at 1 site in Germany.

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 3 inclusion and 1 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 15 Dec 2023. 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 Germany. 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?

Loop Gain (time frame: During one day of diagnostic polysomnography). 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 NCT03532412, which also lists 11 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 15 Dec 2023.

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