- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06370897
Prediction & Mechanisms of Recovery Following IEDS
A Prospective and Retrospective Observational Study of Symptoms and Mechanisms of Recovery in People With Inner Ear Decompression Sickness (IEDS)
Inner Ear Decompression sickness (IEDS) accounts for 20% of all types of decompression sickness (the bends) in divers. The condition commonly affects the peripheral vestibular system (inner ear). IEDS results in acute symptoms of dizzyness (vertigo) and imbalance. Even with the recommended treatment of hyperbaric oxygen therapy some people do not recovery fully. However, even in the presence of a permanent vestibular deficit many people can show a behavioural recovery where symptoms improve over time. Recovery can be aided by vestibular rehabilitation (VR) which is now routine for acute IEDS but was not provided before 2021, and is not widespread across the UK (United Kingdom) or world, meaning people may have a suboptimal recovery.
This project will investigate if and how people recover after an acute episode of IEDS and whether people who had IEDS in the past show changes in the central (brain) processing of vestibular function and in symptoms of dizziness, balance and posture.
This project has two main parts. Part one is a prospective observational study where people with an acute onset of IEDS are serially monitored while they are receiving hyperbaric treatment and VR over 10-14 days. Part two is a retrospective observational study where who have had IEDS in the past 15 years are re-assessed in a one-off session. The tests in both parts involve clinical tests and specialist eye movement recordings that assess vestibular function. We will also determine the site of any vestibular pathology by using selective stimulation of the vestibular end organ or nerve and assess whether there are any changes in how the structure and function of central vestibular pathways in the brain. In people with chronic IEDS with vestibular symptoms we will offer participants a course of VR over 12 weeks and assess whether this is associated with any improvement in symptoms.
Study Overview
Status
Conditions
Detailed Description
Decompression sickness after diving can occur following a rapid ascent. Here, nitrogen, absorbed by the body when breathing compressed air at depth, comes out of solution and forms microbubbles in the blood. Inner ear decompression sickness (IEDS) accounts for approximately 20% of all cases of decompression sickness. The vestibular system is involved in ~85% cases of IEDS resulting in symptoms of vertigo, nausea, vomiting and unsteadiness with hearing loss and tinnitus.
The strong association of IEDS with a patent foramen ovale (50-73% of cases) suggests that a shunted venous gas embolism causes damage to the vestibular apparatus, which is particularly vulnerable due to its low perfusion and thus slow inert gas washout, compared to the cochlea and other brain structures. It is hypothesised that the nitrogen bubbles within the blood vessels trigger an inflammatory reaction in the endothelium with a coagulation cascade that leads to hypoxic injury and/or that there is direct damage to the membranous labyrinth. Animal models of rapid decompression suggest that it can cause a haemorrhage within the labyrinth with ectopic bone growth and fibrosis occurring over the next month. Advances in the imaging of the inner ear using a gadolinium-based contrast agent (GBCA) allow us to explore structural changes in human divers. Imaging can also help to differentially diagnose another potential cause of diving induced dizziness, superior structural dehiscence syndrome
Decompression sickness and the subsequent inflammatory response requires emergency treatment using with hyperbaric oxygen. The effects of hyperbaric therapy and rehabilitation are not uniform across participants, factors affecting recovery include a high clinical score on admission and a delay in hyperbaric recompression of over 6 hours. Complete recovery is seen in only about 30% of cases. Previous studies have highlighted that people who do not fully recover can have a variety of symptoms that can affect work, hobbies and well-being. These include feelings of instability in some situations (working at a height and with movement) and imbalance in the dark or when changing position.
In people with permanent vestibular pathology, symptoms can still improve due to central adaptive processes within the brain termed vestibular compensation. Clinical studies in other types of peripheral vestibular dysfunction show that it is possible to facilitate the compensation process and symptom recovery through vestibular rehabilitation. Early access to vestibular rehabilitation is now routine practice at the Diving Diseases Research Centre (DDRC) where patients are treated in the South-West UK. This is coupled to diagnosis and monitoring of vestibular function using objective laboratory tests (rotary testing) and clinical tests.
Animal studies highlight the mechanisms underlying vestibular compensation following a peripheral nerve lesion. These focus on changes in the interconnections between brainstem nuclei (e.g. vestibular nuclei) and the cerebellum and re-weighting of the relative importance of multi-sensory sensory inputs. Human studies in chronic peripheral dysfunction also suggest there are recovery-related changes in cortical areas that normally process vestibular information over time. Functional changes in the acute stages include an increase in contralesional activity in the parietoinsular vestibular cortex as well as interlinked subcortical areas (posterolateral thalamus, anterior cingulate gyrus, pontomesencephalic brainstem, hippocampus) with a decrease in activity was seen in the visual, somatosensory and auditory cortices. Structural changes over the first 3 months post lesion include increases in grey matter volume in the vestibular cortex, bilateral hippocampus, visual cortices and the cerebellum.
Within the DDRC vestibular rehabilitation has only been routinely undertaken for people diagnosed with IEDS since 2021. As complete recovery is seen in only about 30% of cases [9]; this suggests that there may be a cohort of patients with residual vestibular symptoms. In surveys of the aural and vestibular effects of diving, including those conducted by the DDRC, 79% (of 790 respondents) have reported aural related problems after learning to dive. Of those with reported problems 46% did not seek any medical advice and 39% specifically reported dizziness / vertigo. In total this suggests that at least 14% of all divers may have undiagnosed vestibular problems that could benefit from vestibular rehabilitation. A case review highlights that since 1999 there have been 79 cases of clinically diagnosed IEDS at the DDRC. Therefore, there is a need to assess and provide rehabilitation support to people with past IEDS and potentially in the future a larger cohort of divers with previously undiagnosed symptoms.
This study plans to:
undertake a prospective observational study where people with acute onset IEDS are followed up. This will include the current battery of clinical and laboratory (rotary) tests but also additional optional clinical and physiological testing (Vestibular Evoked Myogenic Potentials VEMPs), imaging (Diffusor Tensor Imaging DTI and functional Magnetic Resonance Imaging f MRI) and semis-structured interviews in the acute (1-14 days) and chronic (3 months and 12 months) stage.
We will also:
undertake a retrospective cross-sectional study of people who have previously been managed for IEDS by the DDRC. Here we will undertake the same battery of tests as for the prospective study which includes measures of potential risk factors and patient reported outcome measures. We will also take this opportunity to explore people's symptoms post IEDS and their views on future rehabilitation trials. In those with remaining vestibular symptoms and signs we will provide advice on vestibular rehabilitation by qualified personnel with follow up as required. We will compare our data to a cohort of healthy controls of a similar age and gender distribution.
Study Type
Enrollment (Estimated)
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Population: Divers
Exposure: Dive resulting in IEDS symptoms
Description
Prospective Study
Inclusion
Divers admitted with suspected IEDS
Exclusion
Medically unstable
Unstable orthopaedic deficits
Retrospective study
Inclusion
Divers diagnosed with IEDS at DDRC within past 10 years
Exclusion
We will include all co-morbidities as these could affect prognosis and recovery following IEDS.
Healthy control comparator group :
Normative data will be gathered on an age matched group. There will be at least 10 participants for each decade (<30yrs ,30-40yrs, 40-50 yrs,50-60yrs,60-70 yr.)
Inclusion criteria: Adults over 18 years
Exclusion criteria: Neurological, sensory or orthopaedic conditions that could affect balance.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
---|
Prospective Cohort
Divers admitted with suspected IEDS
|
Retrospective Cohort
Divers diagnosed with Inner ear decompression sickness (IEDS) at Deep Diving Research Centre within past 10 years
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Side of peripheral vestibular damage: Prospective cohort
Time Frame: T0=baseline within 24 hrs of IEDS in the prospective cohort
|
Side (left or right) of vestibular dysfunction as determine by video head impulse test (v HIT) testing
|
T0=baseline within 24 hrs of IEDS in the prospective cohort
|
Site of peripheral vestibular damage: Prospective cohort
Time Frame: T0=baseline within 24 hrs of IEDS in the prospective cohort
|
Site of dysfunction: semi-circular canals affected as determine by v HIT testing.
One or a combination of Horizontal, anterior or posterior canals.
|
T0=baseline within 24 hrs of IEDS in the prospective cohort
|
Extent of peripheral vestibular damage: Prospective cohort
Time Frame: T0=baseline within 24 hrs of IEDS in the prospective cohort
|
VOR gain (unit less) as measured by v HIT at T0 (Range 0-1 higher values are better outcome)
|
T0=baseline within 24 hrs of IEDS in the prospective cohort
|
Side of peripheral vestibular damage: Retrospective cohort
Time Frame: 1 time point: 0-10 years post injury
|
Side (left or right) of vestibular dysfunction as determine by video head impulse test (v HIT) testing
|
1 time point: 0-10 years post injury
|
Site of peripheral vestibular damage:Retrospective cohort
Time Frame: 1 time point: 0-10 years post injury
|
Site of dysfunction: semi-circular canals affected as determine by v HIT testing.One or a combination of Horizontal, anterior or posterior canals.
|
1 time point: 0-10 years post injury
|
Extent of peripheral vestibular damage:Retrospective cohort
Time Frame: 1 time point: 0-10 years post injury
|
VOR gain (unit less) at T0 (Range 0-1 higher values are better outcome)
|
1 time point: 0-10 years post injury
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
VOR gain v HIT: Prospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
Change from baseline (T0) in VOR gain assessed through V HIT test .
Gain is unit less and range from 0-1 where higher values indicate a better clinical outcome.
|
7-10 days , 3 months and 12 months post injury
|
VOR gain: Prospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
Change from baseline (T0) in VOR gain assessed through sinusoidal rotation in the dark .
Gain is unit less and range from 0-1 where higher values indicate a better clinical outcome.
|
7-10 days , 3 months and 12 months post injury
|
VOR Time constant:Prospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
Change from baseline (T0)in VOR time constant in response to a step rotation (initial 140°/s acceleration/deceleration and a 60°/s fixed-chair velocity) stimulus .
Time constant (seconds) where a higher time constant is clinically better.
Range 0-40s.
|
7-10 days , 3 months and 12 months post injury
|
Patient reported outcome measure: Prospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
Change from baseline (T0) in PROM (patient reported outcome measure) vertigo severity scale.15
questions rated 0-4.
Score range =0-60 where lower scores indicate a better clinical outcome
|
7-10 days , 3 months and 12 months post injury
|
Clinical measure of walking: Prospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
Change from baseline (T0) in Dynamic Gait Assessment (DGA).
Eight tasks scored 0-3.
Total range = 0-24 with a higher score indicating better walking ability.
|
7-10 days , 3 months and 12 months post injury
|
Clinical measure of balance: Prospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
Change from baseline (T0) in Clinical measures of balance sharpened Romberg (tandem stance).
The length of time a person is able to stand in the eyes open, tandem stance position is recorded up to a maximum of 30 seconds.
|
7-10 days , 3 months and 12 months post injury
|
Posturography: Prospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
Change from baseline (T0) in Postural sway quotient.
Postural sway (mm/s) is measured via force plates.
The ratio of the sway with eyes open and eyes closed is calculated (unitless ratio).
|
7-10 days , 3 months and 12 months post injury
|
Perception of verticality: Prospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
Change from baseline (T0) in Rod and Disk test: The ability to orientate a line to vertical is assessed with / without visual distractors.
The error from vertical is recorded in degrees.
Outcomes range from 0-180 degrees where lower numbers indicate better verical perception.
|
7-10 days , 3 months and 12 months post injury
|
Functional MRI response to an optokinetic stimulus: Prospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
Change from baseline (T0) in Regions of interest will also assess changes in activation with an optokinetic stimulus compared to rest in cortical and subcortical sites that process vestibular information namely the insulo-parietal cortex and hippocampus and sites that process other sensory information namely the visual cortex and somatosensory cortex
|
7-10 days , 3 months and 12 months post injury
|
Vestibular Evoked myogenic Potentials latency: Prospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
Change from baseline (T0) in Galvanic and Auditory Vestibular Evoked myogenic Potentials (VEMPs) will be assessed and the latency of evoked responses measured in milliseconds.
|
7-10 days , 3 months and 12 months post injury
|
Vestibular Evoked myogenic Potentials amplitude: Prospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
Change from baseline (T0) in Galvanic and Auditory Vestibular Evoked myogenic Potentials (VEMPs) will be assessed and the amplitude of evoked responses measured in millivolts.
|
7-10 days , 3 months and 12 months post injury
|
VOR gain: Retrospective Study
Time Frame: 7-10 days , 3 months and 12 months post injury
|
VOR gain assessed through sinusoidal rotation in the dark .
Gain is unit less and range from 0-1 where higher values indicate a better clinical outcome.
|
7-10 days , 3 months and 12 months post injury
|
VOR Time constant: Retrospective Study
Time Frame: 1 time point: 0-10 years post injury
|
VOR time constant in response to a step rotation (initial 140°/s acceleration/deceleration and a 60°/s fixed-chair velocity) stimulus .
Time constant (seconds) where a higher time constant is clinically better.
Range 0-40s.
|
1 time point: 0-10 years post injury
|
Patient reported outcome measure: Retrospective Study
Time Frame: 1 time point: 0-10 years post injury
|
PROM (patient reported outcome measure) vertigo severity scale.15
questions rated 0-4.
Score range =0-60 where lower scores indicate a better clinical outcome
|
1 time point: 0-10 years post injury
|
Clinical measure of walking: Retrospective Study
Time Frame: 1 time point: 0-10 years post injury
|
Dynamic Gait Assessment (DGA).
Eight tasks scored 0-3.
Total range = 0-24 with a higher score indicating better walking ability.
|
1 time point: 0-10 years post injury
|
Clinical measure of balance: Retrospective Study
Time Frame: 1 time point: 0-10 years post injury
|
Clinical measures of balance sharpened Romberg (tandem stance).
The length of time a person is able to stand in the eyes open, tandem stance position is recorded up to a maximum of 30 seconds.
|
1 time point: 0-10 years post injury
|
Posturography: Retrospective Study
Time Frame: 1 time point: 0-10 years post injury
|
Postural sway quotient.
Postural sway (mm/s) is measured via force plates.
The ratio of the sway with eyes open and eyes closed is calculated (unitless ratio).
|
1 time point: 0-10 years post injury
|
Perception of verticality: Retrospective Study
Time Frame: 1 time point: 0-10 years post injury
|
Rod and Disk test: The ability to orientate a line to vertical is assessed with / without visual distractors.
The error from vertical is recorded in degrees.
Outcomes range from 0-180 degrees where lower numbers indicate better verical perception.
|
1 time point: 0-10 years post injury
|
Functional MRI response to an optokinetic stimulus: Retrospective Study
Time Frame: 1 time point: 0-10 years post injury
|
Regions of interest will also assess changes in activation with an optokinetic stimulus compared to rest in cortical and subcortical sites that process vestibular information namely the insulo-parietal cortex and hippocampus and sites that process other sensory information namely the visual cortex and somatosensory cortex
|
1 time point: 0-10 years post injury
|
Vestibular Evoked myogenic Potentials latency: Retrospective Study
Time Frame: 1 time point: 0-10 years post injury
|
Galvanic and Auditory Vestibular Evoked myogenic Potentials (VEMPs) will be assessed and the latency of evoked responses measured in milliseconds.
|
1 time point: 0-10 years post injury
|
Vestibular Evoked myogenic Potentials amplitude: Retrorospective Study
Time Frame: 1 time point: 0-10 years post injury
|
Galvanic and Auditory Vestibular Evoked myogenic Potentials (VEMPs) will be assessed and the amplitude of evoked responses measured in millivolts.
|
1 time point: 0-10 years post injury
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- McDonnell MN, Hillier SL. Vestibular rehabilitation for unilateral peripheral vestibular dysfunction. Cochrane Database Syst Rev. 2015 Jan 13;1:CD005397. doi: 10.1002/14651858.CD005397.pub4.
- Gempp E, Louge P. Inner ear decompression sickness in scuba divers: a review of 115 cases. Eur Arch Otorhinolaryngol. 2013 May;270(6):1831-7. doi: 10.1007/s00405-012-2233-y. Epub 2012 Oct 26.
- Tremolizzo L, Malpieri M, Ferrarese C, Appollonio I. Inner-ear decompression sickness: 'hubble-bubble' without brain trouble? Diving Hyperb Med. 2015 Jun;45(2):135-6.
- Mitchell SJ, Doolette DJ. Pathophysiology of inner ear decompression sickness: potential role of the persistent foramen ovale. Diving Hyperb Med. 2015 Jun;45(2):105-10.
- Landolt JP, Money KE, Topliff ED, Ackles KN, Johnson WH. Induced vestibular dysfunction in squirrel monkeys during rapid decompression. Acta Otolaryngol. 1980;90(1-2):125-9. doi: 10.3109/00016488009131707.
- Landolt JP, Money KE, Topliff ED, Nicholas AD, Laufer J, Johnson WH. Pathophysiology of inner ear dysfunction in the squirrel monkey in rapid decompression. J Appl Physiol Respir Environ Exerc Physiol. 1980 Dec;49(6):1070-82. doi: 10.1152/jappl.1980.49.6.1070.
- Kurata N, Kawashima Y, Ito T, Fujikawa T, Nishio A, Honda K, Kanai Y, Terasaki M, Endo I, Tsutsumi T. Advanced Magnetic Resonance Imaging Sheds Light on the Distinct Pathophysiology of Various Types of Acute Sensorineural Hearing Loss. Otol Neurotol. 2023 Aug 1;44(7):656-663. doi: 10.1097/MAO.0000000000003930. Epub 2023 Jun 29.
- Song CI, Pogson JM, Andresen NS, Ward BK. MRI With Gadolinium as a Measure of Blood-Labyrinth Barrier Integrity in Patients With Inner Ear Symptoms: A Scoping Review. Front Neurol. 2021 May 20;12:662264. doi: 10.3389/fneur.2021.662264. eCollection 2021.
- Vargas-Figueroa VM, Caceres-Chacon M, Labat EJ. Scuba Diving-Induced Inner-Ear Pathology: Imaging Findings of Superior Semicircular Canal and Tegmen Tympani Dehiscence. Am J Case Rep. 2024 Jan 2;25:e941558. doi: 10.12659/AJCR.941558.
- Gempp E, Louge P, de Maistre S, Morvan JB, Vallee N, Blatteau JE. Initial Severity Scoring and Residual Deficit in Scuba Divers with Inner Ear Decompression Sickness. Aerosp Med Hum Perform. 2016 Aug;87(8):735-9. doi: 10.3357/AMHP.4535.2016.
- Curthoys IS, Halmagyi GM. Vestibular compensation: a review of the oculomotor, neural, and clinical consequences of unilateral vestibular loss. J Vestib Res. 1995 Mar-Apr;5(2):67-107.
- Darlington CL, Smith PF. Molecular mechanisms of recovery from vestibular damage in mammals: recent advances. Prog Neurobiol. 2000 Oct;62(3):313-25. doi: 10.1016/s0301-0082(00)00002-2.
- Bense S, Bartenstein P, Lochmann M, Schlindwein P, Brandt T, Dieterich M. Metabolic changes in vestibular and visual cortices in acute vestibular neuritis. Ann Neurol. 2004 Nov;56(5):624-30. doi: 10.1002/ana.20244.
- Hong SK, Kim JH, Kim HJ, Lee HJ. Changes in the gray matter volume during compensation after vestibular neuritis: a longitudinal VBM study. Restor Neurol Neurosci. 2014;32(5):663-73. doi: 10.3233/RNN-140405.
- Helmchen C, Klinkenstein J, Machner B, Rambold H, Mohr C, Sander T. Structural changes in the human brain following vestibular neuritis indicate central vestibular compensation. Ann N Y Acad Sci. 2009 May;1164:104-15. doi: 10.1111/j.1749-6632.2008.03745.x.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 337421
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Decompression Sickness
-
Assaf-Harofeh Medical CenterCompletedRecompression Treatment After Decompression SicknessIsrael
-
University of PennsylvaniaUniversity of Maryland; Office of Naval Research (ONR)CompletedDecompression Sickness | DysbarismUnited States
-
University Hospital, BrestCompleted
-
BioAegis Therapeutics Inc.Not yet recruitingDecompression Sickness
-
Cancer Institute and Hospital, Chinese Academy...CompletedIntubation;DifficultChina
-
University Hospital of SplitUniversity of MarylandCompletedDecompression Sickness | SCUBA DivingUnited States, Croatia
-
Seoul National University HospitalSMG-SNU Boramae Medical CenterCompleted
-
Duke UniversityUnited States Department of DefenseCompletedAcute Mountain Sickness | Decompression SicknessUnited States
-
Kaohsiung Medical University Chung-Ho Memorial...CompletedAnesthesia Intubation ComplicationsTaiwan
-
Centre Hospitalier Universitaire de Saint EtienneCompleted