Exercise Induced Laryngeal Obstruction (EILO)NCT04620343
HelpILO - RCT on EILO Treatment
A study testing A: Breathing advice with bio-feedback, B: Breathing advice with bio-feedback, Inspiratory muscle training (IMT) and C: Breathing advice with bio-feedback, Speech Therapy in people with Exercise Induced Laryngeal Obstruction (EILO), run by Haukeland University Hospital at 1 site in Norway.
Trial summary
Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high intensity exercise. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Exercise Induced Laryngeal Obstruction (EILO)
- What is being tested?
- A: Breathing advice with bio-feedback, B: Breathing advice with bio-feedback, Inspiratory muscle training (IMT) and C: Breathing advice with bio-feedback, Speech Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 1 siteNorway
- Study dates
- 1 Jan 2021to 31 Dec 2036
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- EILO with CLE score at peak exercise graded as ≥ 2 at glottic or supraglottic level and
- Respiratory complaints to an extent that the patient wants further treatment and follow-up.
Who cannot join
- Breathing problems caused by disorders other than EILO or well controlled asthma.
- Perceived to be unable to perform repeated maximal cardiopulmonary treadmill exercise tests, or failing to accept the procedures required for repeated successful CLE tests, or unable to perform any of the other examinations required by the protocol.
- Abnormal anatomy at rest in the laryngeal region or the upper airways.
- Age below 12 years
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Norway1 site, 1 recruiting
- Recruiting
Haukeland University Hospital, Children and Youth Clinic
Bergen, Vestland, 5021
Hege H Clemm, MD, PhD, 004792606661, hege.synnove.havstad.clemm@helse-bergen.no
Thomas Halvorsen, MD, PhD, 004792464843, thomas.halvorsen@helse-bergen.no
About this study
Official title: Exercise Induced Laryngeal Obstruction; a Randomized Controlled Treatment Trial
Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high intensity exercise.
Read the detailed description
Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high intensity exercise.
Studies indicate that EILO responds positively to treatment interventions; however, the investigators lack randomized controlled studies to confirm this (10-15). This study aims to provide evidence-based information on interventions commonly applied to treat EILO. Background: Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high intensity exercise. Empirical data suggest that EILO consists of different subtypes that require different therapeutic approaches. However, currently applied treatment schemes do not rest on randomized controlled trials. This study aims to provide evidence-based information on treatment schemes commonly applied in patients with EILO.
Methods: Consenting patients consecutively diagnosed with EILO at Haukeland University Hospital will be randomized into four different conservative treatment arms, selected on the basis of promising reports from non-randomized studies: (A) standardized information and breathing advice only (IBA), (B) IBA plus inspiratory muscle training, (C) IBA plus speech therapy, and (D) IBA plus provision of both inspiratory muscle training and speech therapy. Differential effects in predefined EILO subtypes will be addressed. Patients failing the conservative approach and otherwise qualifying for surgical treatment by current department policy will be considered for randomization into (E) standard or (F) minimal laser supraglottoplasty, and a "wait-and-see" control group. Power calculations will be based on the main outcomes, laryngeal adduction during peak exercise, rated by a validated scoring system before and after the interventions.
Discussion: The study will provide evidence-based information on the treatment of EILO, listed as a priority in a recent statement issued by the European Respiratory Society, requested by clinicians and researchers engaged in this area, and relevant to 5-7% of young people.
- Being tested
- A: Breathing advice with bio-feedback, B: Breathing advice with bio-feedback, Inspiratory muscle training (IMT), C: Breathing advice with bio-feedback, Speech Therapy, D: Breathing advice with bio-feedback, IMT and Speech Therapy, A: If CLE-test unchanged, additional IMT and Speech Therapy
- Keywords
- Larynx, Obstruction, Exercise
- Medical subject headings
- Laryngeal Diseases, Bites and Stings, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A: Breathing advice with bio-feedbackProcedure or surgery
Information and breathing advice with biofeedback will serve as an active comparator in this study, and time allowed for IBA and biofeedback in this study will be max 30 min. The teaching will be provided by the attending physician and the test leader. The session will follow a strict checklist. After the laryngoscope has been secured in correct position the patient will be shown his/her larynx on the screen, providing the patient with basic knowledge on laryngeal anatomy and function in a calm atmosphere before the CLE-test. After, the patients will be trained to make any symptoms abate, and a good breathing posture and how to optimally use their breathing muscles.
B: Breathing advice with bio-feedback, Inspiratory muscle training (IMT)Procedure or surgery
Breathing advise and IMT. The inspiratory muscle training (IMT) will build on the information the patients have obtained during the IBA and biofeedback session. The IMT will focus on training endurance and coordination of the PCA muscle, aiming to reduce fatigue of the abducting capacity of the larynx and to enhance coordination and create a sense of laryngeal control. When performing the IMT sessions, it is of utmost importance that a functional diaphragmatic breathing pattern has been established, and that this breathing pattern is maintained throughout all the IMT sessions. Once the patient has demonstrated that he/she is able to perform breathing according to these principles, the IMT session will follow a detailed protocol while wearing a flexible laryngoscope and settings and techniques are adjusted to ensure max open larynx. The patient will perform IMT training at home as instructed and have video meetings one and three weeks after initial training to observe progress.
C: Breathing advice with bio-feedback, Speech TherapyProcedure or surgery
The training period with the speech therapist takes three days, divided into 6 sessions. The training is continued at home, implementing the techniques during physical activity and at rest. The aim of the speech therapy is to help the patients to develop a strategy on how to control his/her larynx during exercise, and to be able to continue exercising without experiencing dramatic EILO incidents. They will be informed that the best approach is to start practicing while performing low to moderate intensity exercise, and then gradually increase the intensity as they become more confident. It will be emphasized that the new breathing technique they are about to adopt will need to be repeated until it becomes adapted as a part of their automated breathing pattern. Patients will be followed up with video meetings one and three weeks after initial training to observe progress.
D: Breathing advice with bio-feedback, IMT and Speech TherapyProcedure or surgery
All treatments as described above.
A: If CLE-test unchanged, additional IMT and Speech TherapyProcedure or surgery
All treatments as described above.
Surgery 1: Supraglottoplasty - full procedure under general anesthesiaProcedure or surgery
Endoscopic supraglottoplasty with carbon dioxide laser and cold steel microlaryngeal instruments. The patient is intubated with an armored laser-tube which is positioned in the posterior midline to protect this area from laser injury. The laryngoscope is positioned into the vallecula and the surgery is visualized through an operation-microscope. CO2-laser beams of 2-4W focused with micro spot is utilized. Releasing incisions are made at the anterior border of both AEFs. The depth of the incisions are limited to the cranial border of the ventricular folds. The cuneiform tubercles including their surrounding mucosa are removed in a circular pattern before the two incisions are adjoined, thus creating a drop shaped excision. Care is taken to avoid scarring. It is recommended to protect the posterior commissure and the piriform sinus with wet tissue cloths. In case of perioperative edema of the laryngeal mucosa, corticosteroids are administrated to prevent laryngeal edema post-operatively.
Surgery 2: Supraglottoplasty - mini-invasive procedure under general anesthesiaProcedure or surgery
Endoscopic supraglottoplasty with carbon dioxide laser. The patients are intubated with an armored laser-tube, which is positioned in the posterior midline to protect this area from laser injury. The laryngoscope (Benjamin/Lindholm) is positioned into the vallecula and the surgery is visualized through an operation-microscope. CO2-laser beams of 2-4W focused with micro spot are utilized. Four punctures will be made along the lateral borders of both aryepiglottic folds bilateral, thus creating a row of small punctures parallel to the rim of the aryepiglottic folds. The punctions should not be deeper than the incision in the "full procedure" (above); i.e. less than 5 millimeter, and care must be taken to avoid heat affecting the nervus recurrens posteriorly. Care is taken to avoid scarring and collateral thermal injury. It is recommended to protect the posterior commissure and the piriform sinus with wet tissue cloths. No antibiotic prophylaxis is administered.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1, Group 1 | Active comparator | Patients are provided with basic information and breathing advice with biofeedback (IBA).
This is the reference treatment against which the other methods will be measured. Receives: Procedure: A: Breathing advice with bio-feedback |
| Phase 1, Group 2 | Experimental | Patients are provided with basic information and breathing advice with biofeedback (IBA) and treated with inspiratory muscle training (IMT) Receives: Procedure: B: Breathing advice with bio-feedback, Inspiratory muscle training (IMT) |
| Phase 1, Group 3 | Experimental | Patients are provided with basic information and breathing advice with biofeedback (IBA) and treated with speech therapy Receives: Procedure: C: Breathing advice with bio-feedback, Speech Therapy |
| Phase 1, Group 4 | Experimental | Patients are provided with basic information and breathing advice with biofeedback (IBA) and treated with inspiratory muscle training (IMT) and speech therapy Receives: Procedure: D: Breathing advice with bio-feedback, IMT and Speech Therapy |
| Phase 2, Group 1 | No intervention | Groups 2,3,4 in Phase 1 Wait for therapy effect |
| Phase 2, Group 2 | Experimental | If patients from Phase 1, Group 1 (reference treatment) have unchanged CLE-scoring, they are treated with inspiratory muscle training (IMT) and speech therapy. Receives: Procedure: A: If CLE-test unchanged, additional IMT and Speech Therapy |
| Phase 3, Group 1 | Experimental | Treated with Surgery, supraglottoplasty - full procedure Receives: Procedure: Surgery 1: Supraglottoplasty - full procedure under general anesthesia |
| Phase 3, Group 2 | Experimental | Treated with Surgery, supraglottoplasty mini-invasive procedure Receives: Procedure: Surgery 2: Supraglottoplasty - mini-invasive procedure under general anesthesia |
| Phase3, Group 3 | No intervention | Non-surgery control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Questionnaires
All patients will complete custom-made questionnaires recording demographic background variables and symptom scores. The questionnaires focus mainly on respiratory symptoms experienced by the patients, treatment they have been exposed to, and diagnoses they have been assigned. Relevant co-morbidities will also be recorded.
Measured: Day 1
Pulmonary function and exercise test - Spirometry 1
Recording of expiratory and inspiratory volumes and flows will be recorded: Forced expiratory and inspiratory volume capacity (FVC and FIVC). Volumes measured in liters
Measured: Through study completion, on average 6 months
Pulmonary function and exercise test - Spirometry 2
Recording of expiratory and inspiratory volumes and flows will be recorded: forced expiratory and inspiratory volume in first second (FEV1 and FIV1). Volumes measured in liters
Measured: Through study completion, on average 6 months
Pulmonary function and exercise test - Spirometry 3
Recording of expiratory and inspiratory volumes and flows will be recorded: forced expiratory and inspiratory flow at 50% of FVC (FEF and FIF50) and at 25-75% of FVC (FEF and FIF25-75). Volumes measured in liters.
Measured: Through study completion, on average 6 months
Continuous Laryngoscopy Exercise test (CLE-test) and scoring
CLE-scores from the video recordings from the CLE-test will be evaluated. Two highly experienced raters will score all CLE tests according to a system that has been published previously. CLE scoring of glottic and supraglottic obstruction, grades 0 to 4.
Measured: Through study completion, on average 6 months
Cardiopulmonary exercise (CPX) data - Variables of gas exchange
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Variables of gas exchange are measured breath-by-breath. Oxygen absorption measured in mL(min)/kg. Co2 production and O2 production in mL/min.
Measured: Through study completion, on average 6 months
Cardiopulmonary exercise (CPX) data - duration of run
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Duration of run is recorded in minutes and seconds.
Measured: Through study completion, on average 6 months
Cardiopulmonary exercise (CPX) data - distance of run
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Distance of run is recorded in meters
Measured: Through study completion, on average 6 months
Cardiopulmonary exercise (CPX) data - oxygen consumption
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Variables of oxygen consumption will be recorded. Oxygen consumption is measured in (mL/min)/kg
Measured: Through study completion, on average 6 months
Cardiopulmonary exercise (CPX) data - CO2 production
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Variables of CO2 production will be recorded in mL/minute.
Measured: Through study completion, on average 6 months
Cardiopulmonary exercise (CPX) data - respiratory rates.
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Variables of respiratory and tidal volumes will be recorded in liters and ratios calculated.
Measured: Through study completion, on average 6 months
Cardiopulmonary exercise (CPX) data - heart rates.
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Variables of heart rates will be recorded in Hf/min.
Measured: Through study completion, on average 6 months
Cardiopulmonary exercise (CPX) data - Exercise tidal flow/volume loops
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Exercise tidal flow/volume loops will be obtained at fixed interval during the session by plotting air flow (l/sec) and air volume the patient breathes during testing.
Measured: Through study completion, on average 6 months
Continuous laryngoscopy exercise (CLE) with pressure recordings
Translaryngeal resistance will be measured during CLE-testing in the third phase. Calculation of resistance will be based on pressure recordings obtained by two pressure sensors placed above and below the larynx, and airflow measured breath by breath by the mouth. Pressure is measured in kPa.
Measured: During Phase 3, average duration 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2020
- Study start1 Jan 2021
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Exercise Induced Laryngeal Obstruction (EILO)Studies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hege H Clemm, MD, PhD, Principal investigator, Haukeland University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04620343
- Sponsor's protocol ID
- 2020/134444
- Status last verified
- Aug 2022
- First submitted
- 9 Oct 2020
- Last updated
- 16 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Halvorsen T, Clemm HSH, Vollsaeter M, Roksund OD. Conundrums of Exercise-related Breathing Problems. Epiglottic, Laryngeal, or Bronchial Obstruction? Am J Respir Crit Care Med. 2020 Nov 15;202(10):e142-e143. doi: 10.1164/rccm.201910-1921IM. No abstract available.
PubMed 32783778Engan M, Engeseth MS, Fevang S, Vollsaeter M, Eide GE, Roksund OD, Halvorsen T, Clemm H. Predicting physical activity in a national cohort of children born extremely preterm. Early Hum Dev. 2020 Jun;145:105037. doi: 10.1016/j.earlhumdev.2020.105037. Epub 2020 Apr 11.
PubMed 32438296Fretheim-Kelly ZL, Halvorsen T, Clemm H, Roksund O, Heimdal JH, Vollsaeter M, Fintl C, Strand E. Exercise Induced Laryngeal Obstruction in Humans and Equines. A Comparative Review. Front Physiol. 2019 Oct 30;10:1333. doi: 10.3389/fphys.2019.01333. eCollection 2019.
PubMed 31736771Sandnes A, Hilland M, Vollsaeter M, Andersen T, Engesaeter IO, Sandvik L, Heimdal JH, Halvorsen T, Eide GE, Roksund OD, Clemm HH. Severe Exercise-Induced Laryngeal Obstruction Treated With Supraglottoplasty. Front Surg. 2019 Jul 31;6:44. doi: 10.3389/fsurg.2019.00044. eCollection 2019.
PubMed 31417908Sandnes A, Andersen T, Clemm HH, Hilland M, Vollsaeter M, Heimdal JH, Eide GE, Halvorsen T, Roksund OD. Exercise-induced laryngeal obstruction in athletes treated with inspiratory muscle training. BMJ Open Sport Exerc Med. 2019 Jan 18;5(1):e000436. doi: 10.1136/bmjsem-2018-000436. eCollection 2019.
PubMed 30792880Fretheim-Kelly Z, Halvorsen T, Heimdal JH, Strand E, Vollsaeter M, Clemm H, Roksund O. Feasibility and tolerability of measuring translaryngeal pressure during exercise. Laryngoscope. 2019 Dec;129(12):2748-2753. doi: 10.1002/lary.27846. Epub 2019 Jan 30.
PubMed 30698834Andersen TM, Sandnes A, Fondenes O, Clemm H, Halvorsen T, Nilsen RM, Tysnes OB, Heimdal JH, Vollsaeter M, Roksund OD. Laryngoscopy Can Be a Valuable Tool for Unexpected Therapeutic Response in Noninvasive Respiratory Interventions. Respir Care. 2018 Nov;63(11):1459-1461. doi: 10.4187/respcare.06674. No abstract available.
PubMed 30389835Clemm HSH, Sandnes A, Vollsaeter M, Hilland M, Heimdal JH, Roksund OD, Halvorsen T. The Heterogeneity of Exercise-induced Laryngeal Obstruction. Am J Respir Crit Care Med. 2018 Apr 15;197(8):1068-1069. doi: 10.1164/rccm.201708-1646IM. No abstract available.
PubMed 29390192Roksund OD, Heimdal JH, Clemm H, Vollsaeter M, Halvorsen T. Exercise inducible laryngeal obstruction: diagnostics and management. Paediatr Respir Rev. 2017 Jan;21:86-94. doi: 10.1016/j.prrv.2016.07.003. Epub 2016 Jul 18.
PubMed 27492717Heimdal JH, Roksund OD, Halvorsen T, Skadberg BT, Olofsson J. Continuous laryngoscopy exercise test: a method for visualizing laryngeal dysfunction during exercise. Laryngoscope. 2006 Jan;116(1):52-7. doi: 10.1097/01.mlg.0000184528.16229.ba.
PubMed 16481809Maat RC, Roksund OD, Olofsson J, Halvorsen T, Skadberg BT, Heimdal JH. Surgical treatment of exercise-induced laryngeal dysfunction. Eur Arch Otorhinolaryngol. 2007 Apr;264(4):401-7. doi: 10.1007/s00405-006-0216-6. Epub 2007 Jan 4.
PubMed 17203312Maat RC, Roksund OD, Halvorsen T, Skadberg BT, Olofsson J, Ellingsen TA, Aarstad HJ, Heimdal JH. Audiovisual assessment of exercise-induced laryngeal obstruction: reliability and validity of observations. Eur Arch Otorhinolaryngol. 2009 Dec;266(12):1929-36. doi: 10.1007/s00405-009-1030-8. Epub 2009 Jul 8.
PubMed 19585139Roksund OD, Maat RC, Heimdal JH, Olofsson J, Skadberg BT, Halvorsen T. Exercise induced dyspnea in the young. Larynx as the bottleneck of the airways. Respir Med. 2009 Dec;103(12):1911-8. doi: 10.1016/j.rmed.2009.05.024. Epub 2009 Sep 26.
PubMed 19782550Maat RC, Hilland M, Roksund OD, Halvorsen T, Olofsson J, Aarstad HJ, Heimdal JH. Exercise-induced laryngeal obstruction: natural history and effect of surgical treatment. Eur Arch Otorhinolaryngol. 2011 Oct;268(10):1485-92. doi: 10.1007/s00405-011-1656-1. Epub 2011 Jun 5.
PubMed 21643933Sandnes A, Andersen T, Hilland M, Ellingsen TA, Halvorsen T, Heimdal JH, Roksund OD. Laryngeal movements during inspiratory muscle training in healthy subjects. J Voice. 2013 Jul;27(4):448-53. doi: 10.1016/j.jvoice.2013.02.010. Epub 2013 May 15.
PubMed 23683807
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exercise Induced Laryngeal Obstruction; a Randomized Controlled Treatment Trial
- ClinicalTrials.gov ID
- NCT04620343
- Acronym / sponsor ID
- 2020/134444
- Keywords
- Larynx, Obstruction, Exercise
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2036 (estimated)
- First posted
- 9 Nov 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.
Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high intensity exercise.
Detailed description
Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high intensity exercise.
Studies indicate that EILO responds positively to treatment interventions; however, the investigators lack randomized controlled studies to confirm this (10-15). This study aims to provide evidence-based information on interventions commonly applied to treat EILO. Background: Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high intensity exercise. Empirical data suggest that EILO consists of different subtypes that require different therapeutic approaches. However, currently applied treatment schemes do not rest on randomized controlled trials. This study aims to provide evidence-based information on treatment schemes commonly applied in patients with EILO.
Methods: Consenting patients consecutively diagnosed with EILO at Haukeland University Hospital will be randomized into four different conservative treatment arms, selected on the basis of promising reports from non-randomized studies: (A) standardized information and breathing advice only (IBA), (B) IBA plus inspiratory muscle training, (C) IBA plus speech therapy, and (D) IBA plus provision of both inspiratory muscle training and speech therapy. Differential effects in predefined EILO subtypes will be addressed. Patients failing the conservative approach and otherwise qualifying for surgical treatment by current department policy will be considered for randomization into (E) standard or (F) minimal laser supraglottoplasty, and a "wait-and-see" control group. Power calculations will be based on the main outcomes, laryngeal adduction during peak exercise, rated by a validated scoring system before and after the interventions.
Discussion: The study will provide evidence-based information on the treatment of EILO, listed as a priority in a recent statement issued by the European Respiratory Society, requested by clinicians and researchers engaged in this area, and relevant to 5-7% of young people.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Phase 1, Group 1 | Active comparator | Procedure: A: Breathing advice with bio-feedbackPatients are provided with basic information and breathing advice with biofeedback (IBA). This is the reference treatment against which the other methods will be measured. |
| Phase 1, Group 2 | Experimental | Procedure: B: Breathing advice with bio-feedback, Inspiratory muscle training (IMT)Patients are provided with basic information and breathing advice with biofeedback (IBA) and treated with inspiratory muscle training (IMT) |
| Phase 1, Group 3 | Experimental | Procedure: C: Breathing advice with bio-feedback, Speech TherapyPatients are provided with basic information and breathing advice with biofeedback (IBA) and treated with speech therapy |
| Phase 1, Group 4 | Experimental | Procedure: D: Breathing advice with bio-feedback, IMT and Speech TherapyPatients are provided with basic information and breathing advice with biofeedback (IBA) and treated with inspiratory muscle training (IMT) and speech therapy |
| Phase 2, Group 1 | No intervention | –Groups 2,3,4 in Phase 1 Wait for therapy effect |
| Phase 2, Group 2 | Experimental | Procedure: A: If CLE-test unchanged, additional IMT and Speech TherapyIf patients from Phase 1, Group 1 (reference treatment) have unchanged CLE-scoring, they are treated with inspiratory muscle training (IMT) and speech therapy. |
| Phase 3, Group 1 | Experimental | Procedure: Surgery 1: Supraglottoplasty - full procedure under general anesthesiaTreated with Surgery, supraglottoplasty - full procedure |
| Phase 3, Group 2 | Experimental | Procedure: Surgery 2: Supraglottoplasty - mini-invasive procedure under general anesthesiaTreated with Surgery, supraglottoplasty mini-invasive procedure |
| Phase3, Group 3 | No intervention | –Non-surgery control group |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- EILO with CLE score at peak exercise graded as ≥ 2 at glottic or supraglottic level and
- Respiratory complaints to an extent that the patient wants further treatment and follow-up.
Key exclusion criteria (4 listed)
- Breathing problems caused by disorders other than EILO or well controlled asthma.
- Perceived to be unable to perform repeated maximal cardiopulmonary treadmill exercise tests, or failing to accept the procedures required for repeated successful CLE tests, or unable to perform any of the other examinations required by the protocol.
- Abnormal anatomy at rest in the laryngeal region or the upper airways.
- Age below 12 years
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 |
|---|---|---|
| A: Breathing advice with bio-feedbackInformation and breathing advice with biofeedback will serve as an active comparator in this study, and time allowed for IBA and biofeedback in this study will be max 30 min. The teaching will be provided by the attending physician and the test leader. The session will follow a strict checklist. After the laryngoscope has been secured in correct position the patient will be shown his/her larynx on the screen, providing the patient with basic knowledge on laryngeal anatomy and function in a calm atmosphere before the CLE-test. After, the patients will be trained to make any symptoms abate, and a good breathing posture and how to optimally use their breathing muscles. | Procedure or surgery | Phase 1, Group 1 |
| B: Breathing advice with bio-feedback, Inspiratory muscle training (IMT)Breathing advise and IMT. The inspiratory muscle training (IMT) will build on the information the patients have obtained during the IBA and biofeedback session. The IMT will focus on training endurance and coordination of the PCA muscle, aiming to reduce fatigue of the abducting capacity of the larynx and to enhance coordination and create a sense of laryngeal control. When performing the IMT sessions, it is of utmost importance that a functional diaphragmatic breathing pattern has been established, and that this breathing pattern is maintained throughout all the IMT sessions. Once the patient has demonstrated that he/she is able to perform breathing according to these principles, the IMT session will follow a detailed protocol while wearing a flexible laryngoscope and settings and techniques are adjusted to ensure max open larynx. The patient will perform IMT training at home as instructed and have video meetings one and three weeks after initial training to observe progress. | Procedure or surgery | Phase 1, Group 2 |
| C: Breathing advice with bio-feedback, Speech TherapyThe training period with the speech therapist takes three days, divided into 6 sessions. The training is continued at home, implementing the techniques during physical activity and at rest. The aim of the speech therapy is to help the patients to develop a strategy on how to control his/her larynx during exercise, and to be able to continue exercising without experiencing dramatic EILO incidents. They will be informed that the best approach is to start practicing while performing low to moderate intensity exercise, and then gradually increase the intensity as they become more confident. It will be emphasized that the new breathing technique they are about to adopt will need to be repeated until it becomes adapted as a part of their automated breathing pattern. Patients will be followed up with video meetings one and three weeks after initial training to observe progress. | Procedure or surgery | Phase 1, Group 3 |
| D: Breathing advice with bio-feedback, IMT and Speech TherapyAll treatments as described above. | Procedure or surgery | Phase 1, Group 4 |
| A: If CLE-test unchanged, additional IMT and Speech TherapyAll treatments as described above. | Procedure or surgery | Phase 2, Group 2 |
| Surgery 1: Supraglottoplasty - full procedure under general anesthesiaEndoscopic supraglottoplasty with carbon dioxide laser and cold steel microlaryngeal instruments. The patient is intubated with an armored laser-tube which is positioned in the posterior midline to protect this area from laser injury. The laryngoscope is positioned into the vallecula and the surgery is visualized through an operation-microscope. CO2-laser beams of 2-4W focused with micro spot is utilized. Releasing incisions are made at the anterior border of both AEFs. The depth of the incisions are limited to the cranial border of the ventricular folds. The cuneiform tubercles including their surrounding mucosa are removed in a circular pattern before the two incisions are adjoined, thus creating a drop shaped excision. Care is taken to avoid scarring. It is recommended to protect the posterior commissure and the piriform sinus with wet tissue cloths. In case of perioperative edema of the laryngeal mucosa, corticosteroids are administrated to prevent laryngeal edema post-operatively. | Procedure or surgery | Phase 3, Group 1 |
| Surgery 2: Supraglottoplasty - mini-invasive procedure under general anesthesiaEndoscopic supraglottoplasty with carbon dioxide laser. The patients are intubated with an armored laser-tube, which is positioned in the posterior midline to protect this area from laser injury. The laryngoscope (Benjamin/Lindholm) is positioned into the vallecula and the surgery is visualized through an operation-microscope. CO2-laser beams of 2-4W focused with micro spot are utilized. Four punctures will be made along the lateral borders of both aryepiglottic folds bilateral, thus creating a row of small punctures parallel to the rim of the aryepiglottic folds. The punctions should not be deeper than the incision in the "full procedure" (above); i.e. less than 5 millimeter, and care must be taken to avoid heat affecting the nervus recurrens posteriorly. Care is taken to avoid scarring and collateral thermal injury. It is recommended to protect the posterior commissure and the piriform sinus with wet tissue cloths. No antibiotic prophylaxis is administered. | Procedure or surgery | Phase 3, Group 2 |
Primary outcome
Questionnaires
Time frame: Day 1
All patients will complete custom-made questionnaires recording demographic background variables and symptom scores. The questionnaires focus mainly on respiratory symptoms experienced by the patients, treatment they have been exposed to, and diagnoses they have been assigned. Relevant co-morbidities will also be recorded.
Pulmonary function and exercise test - Spirometry 1
Time frame: Through study completion, on average 6 months
Recording of expiratory and inspiratory volumes and flows will be recorded: Forced expiratory and inspiratory volume capacity (FVC and FIVC). Volumes measured in liters
Pulmonary function and exercise test - Spirometry 2
Time frame: Through study completion, on average 6 months
Recording of expiratory and inspiratory volumes and flows will be recorded: forced expiratory and inspiratory volume in first second (FEV1 and FIV1). Volumes measured in liters
Pulmonary function and exercise test - Spirometry 3
Time frame: Through study completion, on average 6 months
Recording of expiratory and inspiratory volumes and flows will be recorded: forced expiratory and inspiratory flow at 50% of FVC (FEF and FIF50) and at 25-75% of FVC (FEF and FIF25-75). Volumes measured in liters.
Continuous Laryngoscopy Exercise test (CLE-test) and scoring
Time frame: Through study completion, on average 6 months
CLE-scores from the video recordings from the CLE-test will be evaluated. Two highly experienced raters will score all CLE tests according to a system that has been published previously. CLE scoring of glottic and supraglottic obstruction, grades 0 to 4.
Cardiopulmonary exercise (CPX) data - Variables of gas exchange
Time frame: Through study completion, on average 6 months
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Variables of gas exchange are measured breath-by-breath. Oxygen absorption measured in mL(min)/kg. Co2 production and O2 production in mL/min.
Cardiopulmonary exercise (CPX) data - duration of run
Time frame: Through study completion, on average 6 months
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Duration of run is recorded in minutes and seconds.
Cardiopulmonary exercise (CPX) data - distance of run
Time frame: Through study completion, on average 6 months
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Distance of run is recorded in meters
Cardiopulmonary exercise (CPX) data - oxygen consumption
Time frame: Through study completion, on average 6 months
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Variables of oxygen consumption will be recorded. Oxygen consumption is measured in (mL/min)/kg
Cardiopulmonary exercise (CPX) data - CO2 production
Time frame: Through study completion, on average 6 months
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Variables of CO2 production will be recorded in mL/minute.
Cardiopulmonary exercise (CPX) data - respiratory rates.
Time frame: Through study completion, on average 6 months
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Variables of respiratory and tidal volumes will be recorded in liters and ratios calculated.
Cardiopulmonary exercise (CPX) data - heart rates.
Time frame: Through study completion, on average 6 months
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Variables of heart rates will be recorded in Hf/min.
Cardiopulmonary exercise (CPX) data - Exercise tidal flow/volume loops
Time frame: Through study completion, on average 6 months
A treadmill will run according to a modified Bruce protocol, incrementing speed and/or grade every 1 min, aiming for peak oxygen uptake after 6-14 min. Exercise tidal flow/volume loops will be obtained at fixed interval during the session by plotting air flow (l/sec) and air volume the patient breathes during testing.
Continuous laryngoscopy exercise (CLE) with pressure recordings
Time frame: During Phase 3, average duration 6 months.
Translaryngeal resistance will be measured during CLE-testing in the third phase. Calculation of resistance will be based on pressure recordings obtained by two pressure sensors placed above and below the larynx, and airflow measured breath by breath by the mouth. Pressure is measured in kPa.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2022.
- Background: PubMed 32783778Halvorsen T, Clemm HSH, Vollsaeter M, Roksund OD. Conundrums of Exercise-related Breathing Problems. Epiglottic, Laryngeal, or Bronchial Obstruction? Am J Respir Crit Care Med. 2020 Nov 15;202(10):e142-e143. doi: 10.1164/rccm.201910-1921IM. No abstract available.
- Background: PubMed 32438296Engan M, Engeseth MS, Fevang S, Vollsaeter M, Eide GE, Roksund OD, Halvorsen T, Clemm H. Predicting physical activity in a national cohort of children born extremely preterm. Early Hum Dev. 2020 Jun;145:105037. doi: 10.1016/j.earlhumdev.2020.105037. Epub 2020 Apr 11.
- Background: PubMed 31736771Fretheim-Kelly ZL, Halvorsen T, Clemm H, Roksund O, Heimdal JH, Vollsaeter M, Fintl C, Strand E. Exercise Induced Laryngeal Obstruction in Humans and Equines. A Comparative Review. Front Physiol. 2019 Oct 30;10:1333. doi: 10.3389/fphys.2019.01333. eCollection 2019.
- Background: PubMed 31417908Sandnes A, Hilland M, Vollsaeter M, Andersen T, Engesaeter IO, Sandvik L, Heimdal JH, Halvorsen T, Eide GE, Roksund OD, Clemm HH. Severe Exercise-Induced Laryngeal Obstruction Treated With Supraglottoplasty. Front Surg. 2019 Jul 31;6:44. doi: 10.3389/fsurg.2019.00044. eCollection 2019.
- Background: PubMed 30792880Sandnes A, Andersen T, Clemm HH, Hilland M, Vollsaeter M, Heimdal JH, Eide GE, Halvorsen T, Roksund OD. Exercise-induced laryngeal obstruction in athletes treated with inspiratory muscle training. BMJ Open Sport Exerc Med. 2019 Jan 18;5(1):e000436. doi: 10.1136/bmjsem-2018-000436. eCollection 2019.
- Background: PubMed 30698834Fretheim-Kelly Z, Halvorsen T, Heimdal JH, Strand E, Vollsaeter M, Clemm H, Roksund O. Feasibility and tolerability of measuring translaryngeal pressure during exercise. Laryngoscope. 2019 Dec;129(12):2748-2753. doi: 10.1002/lary.27846. Epub 2019 Jan 30.
- Background: PubMed 30389835Andersen TM, Sandnes A, Fondenes O, Clemm H, Halvorsen T, Nilsen RM, Tysnes OB, Heimdal JH, Vollsaeter M, Roksund OD. Laryngoscopy Can Be a Valuable Tool for Unexpected Therapeutic Response in Noninvasive Respiratory Interventions. Respir Care. 2018 Nov;63(11):1459-1461. doi: 10.4187/respcare.06674. No abstract available.
- Background: PubMed 29390192Clemm HSH, Sandnes A, Vollsaeter M, Hilland M, Heimdal JH, Roksund OD, Halvorsen T. The Heterogeneity of Exercise-induced Laryngeal Obstruction. Am J Respir Crit Care Med. 2018 Apr 15;197(8):1068-1069. doi: 10.1164/rccm.201708-1646IM. No abstract available.
- Background: PubMed 27492717Roksund OD, Heimdal JH, Clemm H, Vollsaeter M, Halvorsen T. Exercise inducible laryngeal obstruction: diagnostics and management. Paediatr Respir Rev. 2017 Jan;21:86-94. doi: 10.1016/j.prrv.2016.07.003. Epub 2016 Jul 18.
- Background: PubMed 16481809Heimdal JH, Roksund OD, Halvorsen T, Skadberg BT, Olofsson J. Continuous laryngoscopy exercise test: a method for visualizing laryngeal dysfunction during exercise. Laryngoscope. 2006 Jan;116(1):52-7. doi: 10.1097/01.mlg.0000184528.16229.ba.
- Background: PubMed 17203312Maat RC, Roksund OD, Olofsson J, Halvorsen T, Skadberg BT, Heimdal JH. Surgical treatment of exercise-induced laryngeal dysfunction. Eur Arch Otorhinolaryngol. 2007 Apr;264(4):401-7. doi: 10.1007/s00405-006-0216-6. Epub 2007 Jan 4.
- Background: PubMed 19585139Maat RC, Roksund OD, Halvorsen T, Skadberg BT, Olofsson J, Ellingsen TA, Aarstad HJ, Heimdal JH. Audiovisual assessment of exercise-induced laryngeal obstruction: reliability and validity of observations. Eur Arch Otorhinolaryngol. 2009 Dec;266(12):1929-36. doi: 10.1007/s00405-009-1030-8. Epub 2009 Jul 8.
- Individual participant dataSharing planned: No
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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.
Hege H Clemm, MD, PhD principal investigator
Haukeland University 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 A: Breathing advice with bio-feedback, B: Breathing advice with bio-feedback, Inspiratory muscle training (IMT) and C: Breathing advice with bio-feedback, Speech Therapy in people with Exercise Induced Laryngeal Obstruction (EILO), run by Haukeland University Hospital at 1 site in Norway.
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 2 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 16 Aug 2022. 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 Norway. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hege H Clemm, MD, PhD (004792606661, hege.synnove.havstad.clemm@helse-bergen.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Questionnaires (time frame: Day 1). The study lists 14 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 NCT04620343, which also lists 20 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 16 Aug 2022.