HelpILO - RCT on EILO Treatment

NCT ID: NCT04620343

Last Updated: 2022-08-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

350 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-01

Study Completion Date

2036-12-31

Brief Summary

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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

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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.

Conditions

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Exercise Induced Laryngeal Obstruction (EILO)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors

Study Groups

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Phase 1, Group 1

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.

Group Type ACTIVE_COMPARATOR

A: Breathing advice with bio-feedback

Intervention Type PROCEDURE

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.

Phase 1, Group 2

Patients are provided with basic information and breathing advice with biofeedback (IBA) and treated with inspiratory muscle training (IMT)

Group Type EXPERIMENTAL

B: Breathing advice with bio-feedback, Inspiratory muscle training (IMT)

Intervention Type PROCEDURE

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.

Phase 1, Group 3

Patients are provided with basic information and breathing advice with biofeedback (IBA) and treated with speech therapy

Group Type EXPERIMENTAL

C: Breathing advice with bio-feedback, Speech Therapy

Intervention Type PROCEDURE

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.

Phase 1, Group 4

Patients are provided with basic information and breathing advice with biofeedback (IBA) and treated with inspiratory muscle training (IMT) and speech therapy

Group Type EXPERIMENTAL

D: Breathing advice with bio-feedback, IMT and Speech Therapy

Intervention Type PROCEDURE

All treatments as described above.

Phase 2, Group 1

Groups 2,3,4 in Phase 1 Wait for therapy effect

Group Type NO_INTERVENTION

No interventions assigned to this group

Phase 2, Group 2

If patients from Phase 1, Group 1 (reference treatment) have unchanged CLE-scoring, they are treated with inspiratory muscle training (IMT) and speech therapy.

Group Type EXPERIMENTAL

A: If CLE-test unchanged, additional IMT and Speech Therapy

Intervention Type PROCEDURE

All treatments as described above.

Phase 3, Group 1

Treated with Surgery, supraglottoplasty - full procedure

Group Type EXPERIMENTAL

Surgery 1: Supraglottoplasty - full procedure under general anesthesia

Intervention Type PROCEDURE

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.

Phase 3, Group 2

Treated with Surgery, supraglottoplasty mini-invasive procedure

Group Type EXPERIMENTAL

Surgery 2: Supraglottoplasty - mini-invasive procedure under general anesthesia

Intervention Type PROCEDURE

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.

Phase3, Group 3

Non-surgery control group

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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A: Breathing advice with bio-feedback

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.

Intervention Type PROCEDURE

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.

Intervention Type PROCEDURE

C: Breathing advice with bio-feedback, Speech Therapy

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.

Intervention Type PROCEDURE

D: Breathing advice with bio-feedback, IMT and Speech Therapy

All treatments as described above.

Intervention Type PROCEDURE

A: If CLE-test unchanged, additional IMT and Speech Therapy

All treatments as described above.

Intervention Type PROCEDURE

Surgery 1: Supraglottoplasty - full procedure under general anesthesia

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.

Intervention Type PROCEDURE

Surgery 2: Supraglottoplasty - mini-invasive procedure under general anesthesia

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.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Haukeland University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hege H Clemm, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Haukeland University Hospital

Locations

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Haukeland University Hospital, Children and Youth Clinic

Bergen, Vestland, Norway

Site Status RECRUITING

Countries

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Norway

Central Contacts

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Hege H Clemm, MD, PhD

Role: CONTACT

004792606661

Thomas Halvorsen, MD, PhD

Role: CONTACT

004792464843

Facility Contacts

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Hege H Clemm, MD, PhD

Role: primary

004792606661

Thomas Halvorsen, MD, PhD

Role: backup

004792464843

References

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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.

Reference Type BACKGROUND
PMID: 32783778 (View on PubMed)

Engan 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.

Reference Type BACKGROUND
PMID: 32438296 (View on PubMed)

Fretheim-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.

Reference Type BACKGROUND
PMID: 31736771 (View on PubMed)

Sandnes 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.

Reference Type BACKGROUND
PMID: 31417908 (View on PubMed)

Sandnes 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.

Reference Type BACKGROUND
PMID: 30792880 (View on PubMed)

Fretheim-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.

Reference Type BACKGROUND
PMID: 30698834 (View on PubMed)

Andersen 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.

Reference Type BACKGROUND
PMID: 30389835 (View on PubMed)

Clemm 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.

Reference Type BACKGROUND
PMID: 29390192 (View on PubMed)

Roksund 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.

Reference Type BACKGROUND
PMID: 27492717 (View on PubMed)

Heimdal 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.

Reference Type BACKGROUND
PMID: 16481809 (View on PubMed)

Maat 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.

Reference Type BACKGROUND
PMID: 17203312 (View on PubMed)

Maat 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.

Reference Type BACKGROUND
PMID: 19585139 (View on PubMed)

Roksund 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.

Reference Type BACKGROUND
PMID: 19782550 (View on PubMed)

Maat 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.

Reference Type BACKGROUND
PMID: 21643933 (View on PubMed)

Sandnes 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.

Reference Type BACKGROUND
PMID: 23683807 (View on PubMed)

Roksund OD, Heimdal JH, Olofsson J, Maat RC, Halvorsen T. Larynx during exercise: the unexplored bottleneck of the airways. Eur Arch Otorhinolaryngol. 2015 Sep;272(9):2101-9. doi: 10.1007/s00405-014-3159-3. Epub 2014 Jul 18.

Reference Type BACKGROUND
PMID: 25033930 (View on PubMed)

Christensen PM, Heimdal JH, Christopher KL, Bucca C, Cantarella G, Friedrich G, Halvorsen T, Herth F, Jung H, Morris MJ, Remacle M, Rasmussen N, Wilson JA; ERS/ELS/ACCP Task Force on Inducible Laryngeal Obstructions. ERS/ELS/ACCP 2013 international consensus conference nomenclature on inducible laryngeal obstructions. Eur Respir Rev. 2015 Sep;24(137):445-50. doi: 10.1183/16000617.00006513.

Reference Type BACKGROUND
PMID: 26324806 (View on PubMed)

Norlander K, Christensen PM, Maat RC, Halvorsen T, Heimdal JH, Moren S, Rasmussen N, Nordang L. Comparison between two assessment methods for exercise-induced laryngeal obstructions. Eur Arch Otorhinolaryngol. 2016 Feb;273(2):425-30. doi: 10.1007/s00405-015-3758-7. Epub 2015 Sep 8.

Reference Type BACKGROUND
PMID: 26351037 (View on PubMed)

Hilland M, Roksund OD, Sandvik L, Haaland O, Aarstad HJ, Halvorsen T, Heimdal JH. Congenital laryngomalacia is related to exercise-induced laryngeal obstruction in adolescence. Arch Dis Child. 2016 May;101(5):443-8. doi: 10.1136/archdischild-2015-308450. Epub 2016 Feb 23.

Reference Type BACKGROUND
PMID: 26906070 (View on PubMed)

Roksund OD, Olin JT, Halvorsen T. Working Towards a Common Transatlantic Approach for Evaluation of Exercise-Induced Laryngeal Obstruction. Immunol Allergy Clin North Am. 2018 May;38(2):281-292. doi: 10.1016/j.iac.2018.01.002. Epub 2018 Feb 19.

Reference Type BACKGROUND
PMID: 29631736 (View on PubMed)

Other Identifiers

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2020/134444

Identifier Type: -

Identifier Source: org_study_id

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