Clinical trial NCT05419960: Audio-vestibular Evaluation of Children and Young Adults With Osteogenesis Imperfecta
Official title: Audio-vestibular Evaluation of Children and Young Adults With Osteogenesis Imperfecta
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Osteogenesis Imperfecta
Keywords: Osteogenesis imperfecta
Vestibular deficits
Correlation between vestibular impairment and radiological findings
Bone abnormalities
Severity of the deafness
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2022-06-15
Enrollment: 44
Sex: ALL
Minimum age (years): 12
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adolescents and young adults with a diagnosis of Osteogenesis Imperfecta of any type and followed by a physician at the Centre de Référence des Maladies Rares des maladies osseuses constitutionnelles (CRMR OI) of Hôpital Necker-Enfants malades.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Central Vestibular Function
timeFrame: 24 months
measure: Subjective Visual Vertical (SVV)
timeFrame: 24 months
measure: Ocular Vestibular Evoked Myogenic Potential (oVEMP)
timeFrame: 24 months
measure: Semi-circular canal function
timeFrame: 24 months
measure: Cervical Vestibular Evoked Myogenic Potential (cVEMP)
timeFrame: 24 months
Secondary outcomes:
measure: Immittance testing
timeFrame: 24 months
measure: Pure-tone audiometry
timeFrame: 24 months
measure: Speech Audiometry
timeFrame: 24 months
measure: Severity of OI
timeFrame: 24 months
measure: Petrous bone Computed Tomography (CT)
timeFrame: 24 months
measure: Magnetic Resonance Imaging (MRI)
timeFrame: 24 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Natalie Loundon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Marine Parodi, MD
role: STUDY_DIRECTOR
References: