Audio-vestibular Evaluation of Children and Young Adults With Osteogenesis Imperfecta

Osteogenesis Imperfecta Clinical Trial

— AVOI  

Official title:

Audio-vestibular Evaluation of Children and Young Adults With Osteogenesis Imperfecta

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05419960
• Other study ID #: APHP220305
• Secondary ID: 2022-A00375-38
• Status: Recruiting
• Start date: December 22, 2022
• Est. completion date: December 22, 2025

Study information

• Verified date: March 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Natalie Loundon, MD, PhD
• Phone: 1 71 39 67 82
• Email: natalie.loundon[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim is to determine whether vestibular deficits are present in OI, then to establish whether a correlation exists between genetic type, severity of OI and audiovestibular phenotype. OI patients aged 12 to 20 years will undergo an audiometric, immittance, and vestibular assessment. When hearing loss is conductive or mixed or in cases where vestibular deficits are identified, a CT scan without injection will be performed. In case of sensorineural hearing loss or abnormal CT results, an MRI will be performed.

Description:

Osteogenesis Imperfecta (OI), or Lobstein's disease, is a form of congenital osteoporosis, with a prevalence between 1/10,000 and 1/20,000 in France. As of 1979, four phenotypes have been described according to severity: moderate (type I), lethal (type II), severe (type III), and moderate-to-severe (type IV). OI exhibits phenotypic and genotypic variability, however, to date no correlations have been established between specific mutations and clinical presentation.

There is a well-established association between OI and hearing loss, however, the reported prevalence of hearing loss varies between 2% to 94.1%.

In patients with OI, Computed Tomography (CT) has revealed bone demineralization that progresses with age.

The extent of the hypodense areas on the CT corresponds to the type of hearing loss:

conductive hearing loss is associated with lesions of the fissula ante fenestram and round and oval windows while mixed hearing loss is associated with additional retrofenestral lesions. Severity of hearing loss is positively correlated with OI-related bone damage in the petrous bone. Magnetic Resonance Imaging (MRI) has also revealed in the pericochlear lesions with soft tissue hypersignal and enhancement on contrast medium injection in the otic capsule. Bone demineralization has also been linked to vestibular deficits, and some studies have reported correlations between Osteogenesis Imperfecta and vestibular deficits in adult patients, however, this relationship is less clear.

The aim of the study is to determine whether vestibular deficits are also present in OI. Furthermore, the study will aim to establish whether a correlation exists between genetic type, severity of OI and audiovestibular phenotype. OI patients aged 12 to 20 years will be recruited and an audiometric, immittance, and vestibular assessment (videonystagmography, video Head Impulse Test (vHIT), vestibular evoked muscular potentials (cVEMP)) will be performed during their annual visit to the Centre de Référence des Maladies Rares des maladies osseuses constitutionnelles (henceforth CRMR OI) of Hôpital Necker-Enfants malades, Paris, France. When hearing loss is conductive, or mixed or in cases where vestibular deficits are identified, a CT scan without injection will be performed for the care. In case of sensorineural hearing loss, or abnormal CT results, an MRI will be proposed for the care. The investigation team will try to establish if there is a significant association between OI and vestibular deficit, and if so, whether the degree of vestibular impairment is correlated to radiological findings with respect to bone abnormalities, as well as the type and severity of the deafness.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: December 22, 2025
• Est. primary completion date: December 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 20 Years

Eligibility

Inclusion Criteria:

• Patients between the ages of 12-20 years at the time of inclusion

• Diagnosis of Osteogenesis Imperfecta of any type

• Currently followed by a physician at the CRMR OI

• Information and non-opposition of major patients, holders of parental authority and minor patients to participate in the study

Exclusion Criteria:

• Patients with hearing loss of alternate origin e.g. Cochlear nerve deficiency, atresia, etc.

• Neurological or developmental deficits limiting participation

• Cervico-occipital instability e.g. Chiari's malformation

• Limitations in mobility of the spine e.g. scoliosis, spinal fractural fusion

• Ophthalmologic pathologies e.g. strabism or severe refraction disorder

• Patients under AME (State Medical Aid)

• Protected adult patients, adults unable to express their consent, pregnant or breastfeeding women

Related Conditions & MeSH terms

• Osteogenesis Imperfecta

Intervention

Diagnostic Test:
• Vestibular Assessment
During the usual hearing assessment (immittance testing and pure-tone and speech audiometry) carried out by patients, a vestibular assessment will be done for the study to detect vestibular disorders: Videonystagmography (VNG) Is the study of eye movement with the help of infrared googles. Subjective Visual Vertical (SVV) The patient is asked to orient a line on the vertical axis. Video Head Impulse Test (vHIT) Cervical and Ocular Vestibular Evoked Myogenic Potential (cVEMP and oVEMP)
• Petrous bone Computed Tomography (CT)
For patients diagnosed with hearing loss, whether conductive, mixed, and/or a vestibular deficit, a CT scan (without injection) will be proposed for their care. Petrous bone Computed Tomography (CT) is an imaging technique used as the standard method of evaluation of the boney structures in the ear.
• Magnetic Resonance Imaging (MRI)
Patients that have done a CT and for who CT results was abnormal, will additionally require an MRI for their standard care. Magnetic Resonance Imaging (MRI) is an imaging technique used as the standard method of evaluation of the cochlear, retrocochlear and central and peripheral nervous system. An injection of Gadolinium contrast media will be used to enhance certain recordings.

Locations

Country	Name	City	State
France	Hôpital Necker-Enfants Malades	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Central Vestibular Function	Is evaluated by videonystagmography (VNG). The purpose of this test battery is to separate the vestibular disorders from disorders of the central neural system.; Clinical norms will be applied to determine whether the exam is either within normal limits or abnormal.; Research of eventual vestibular disorder to determine if vestibular disorders can be linked to Osteogenesis Imperfecta.	24 months
Primary	Subjective Visual Vertical (SVV)	Utricular Function Research of eventual vestibular disorder to determine if vestibular disorders can be linked to Osteogenesis Imperfecta.; The patient is asked to orient a line on the vertical axis. An angle of 3 degrees from the vertical indicates an otolithic utricular disorder.; Clinical norms will be applied to determine whether the exam is either within normal limits or abnormal.	24 months
Primary	Ocular Vestibular Evoked Myogenic Potential (oVEMP)	Utricular Function Research of eventual vestibular disorder to determine if vestibular disorders can be linked to Osteogenesis Imperfecta.; The oVEMP assesses utricular function and reflects the function of the vestibular nuclei and the crossed vestibulo-ocular reflex (VOR) pathways, mostly contained in the medial longitudinal fasciculus (MLF).; Clinical norms will be applied to determine whether the exam is either within normal limits or abnormal.	24 months
Primary	Semi-circular canal function	Video Head Impulse Test (vHIT). The vHIT assesses the vestibular ocular reflex linked to the semi-circular canal function when stimulated at a high frequency.; Clinical norms will be applied to determine whether the exam is either within normal limits or abnormal.; Research of eventual vestibular disorder to determine if vestibular disorders can be linked to Osteogenesis Imperfecta.	24 months
Primary	Cervical Vestibular Evoked Myogenic Potential (cVEMP)	Saccular Function Research of eventual vestibular disorder to determine if vestibular disorders can be linked to Osteogenesis Imperfecta.; The cVEMP assesses the saccular function via the saccular cervical reflex (sternocleidomastoid muscle's activation secondary to saccular auditory stimulation).; Clinical norms will be applied to determine whether the exam is either within normal limits or abnormal.; The otolith organs are comprised of the vestibular saccule and utricule. The cVEMP assesses the saccular function via the saccular cervical reflex (sternocleidomastoid muscle's activation secondary to saccular auditory stimulation).; Clinical norms will be applied to determine whether the exam is either within normal limits or abnormal.; Research of eventual vestibular disorder to determine if vestibular disorders can be linked to Osteogenesis Imperfecta.	24 months
Secondary	Immittance testing	Audiological phenotype Immittance testing can indicate whether middle ear structures are in tact; Middle ear pressure and compliance of the tympanic membrane; Ipsilateral acoustic reflex thresholds	24 months
Secondary	Pure-tone audiometry	Audiometry performance Pure tone audiometry is used to establish the type and degree of hearing loss. This measure is important to characterize the audiological phenotype. Hearing thresholds established in air and bone conduction between 250-8000Hz in each ear.; Pure tone audiometry assessed as normal or abnormal Audiometry is considered abnormal if any threshold is greater than or equal to 25 dB HL.	24 months
Secondary	Speech Audiometry	Audiometry performance Speech audiometry is used to establish the lowest intensity level in dB at which the patient can comprehend 50% of speech. This measure is important to confirm reliability of the pure tone audiometry, and to confirm that speech is both audible and intelligible.; Speech audiometry assessed as normal or abnormal.	24 months
Secondary	Severity of OI	OI medical diagnosis. The OI diagnosis is clinical, based on the following signs: ligament laxity, bluish discoloration of the sclera, hearing loss, vascular tissue abnormalities, hemostatic disorder, elevated basal metabolic rate, renal disorder, neurological disorder, history family.; Depending on symptom severity, OI patient's diagnosis will be classified into on of four phenotypes : moderate (type I), lethal (type II), severe (type III), and moderate-to-severe (type IV).	24 months
Secondary	Petrous bone Computed Tomography (CT)	CT is used to evaluate the presence and localization of petrous bone anomalies, for patients with conductive or mixed hearing loss and/or vestibular deficits.	24 months
Secondary	Magnetic Resonance Imaging (MRI)	MRI is used to evaluate the presence and characteristics of anomalies of inner ear soft tissues, for patients with sensorineural hearing loss and for patients with abnormal CT scan results.	24 months