vestibular failure (vestibular neuritis) MedDRA version: 18.0 Level: PT Classification code 10047386 Term: Vestibular disorder System Organ Class: 10013993 - Ear and labyrinth disorders MedDRA version: 18.0 Level: PT Classification code 10029240 Term: Neuritis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Vasomotal
Pharmaceutical Form: Capsule
INN or Proposed INN: Betahistine
CAS Number: 5638-76-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 24-
Pharma
Sponsors
Hospital of the University of Munich
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients male or female who are at least 18 years old • patient has a history of acute/sub-acute (i.e., within minutes to hours) onset of severe prolonged rotatory vertigo, nausea, and postural imbalance; • the clinical examination reveals horizontal-rotatory spontaneous nystagmus (fast phase) toward the unaffected ear without evidence of a central vestibular lesion, and a pathological head-impulse test (i.e., turning the head of the patient rapidly to the right and left while observing provoked compensatory eye movements) that reveals an ipsilateral deficit of the horizontal semicircular canal (Halmagyi & Curthoys 1988); • caloric irrigation shows hypo-/unresponsiveness of the horizontal canal of the affected ear, i.e., the maximum slow phase velocity during caloric irri-gation with 30°C and 44°C water should be less than 3°/s on the affected side and the asymmetry between the two sides is >25 percent according to “Jongkees’s vestibular paresis formula” (Jongkees et al. 1962; Fife et al. 2000); and • there is a displacement of the subjective visual vertical toward the affected ear without any vertical divergence of the eyes, i.e., without vertical deviation of one eye above the other (Cnyrim et al. 2008). • Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients not able to give consent • a history of vestibular dysfunction before the acute symptom onset or vestibular symptoms beginning more than 3 days before patients were re-cruited; • additional cochlear symptoms, i.e., tinnitus or acute hearing loss before, during, or after the onset of vertigo; • central ocular motor or central vestibular dysfunction; • any other brainstem or cerebellar signs or symptoms or abnormal findings on the MRI in the brainstem or cerebellum in diffusion-weighted images or hyperintense lesions in T2-weighted images in combination with contrast enhancement in T1-weighted images; • other known vestibular disorders such as vestibular migraine, Menière´s disease/syndrome, phobic postural vertigo, benign paroxysmal po-sitioning vertigo; • central disorders such as paroxysmal brainstem attacks; • contraindications for treatment with betahistine-dihydrochloride as bron-chiale asthma, pheochromocytoma, • pregnancy or breast-feeding, • severe dysfunction of liver or kidney, ulcer of the stomach or duodenum, • treatment with other antihistaminic drugs; • known severe coronary heart disease or heart failure, • persistent hypertension with systolic blood pressure > 180 mmHg or diastolic BP > 110 mmHg that cannot be controlled by antihypertensive thera-py, • life expectancy < 3 months, other serious illness, e.g., severe hepatic, cardiac or renal failure, acute myocardial infarction, neoplasm or a com-plex disease that may confound treatment assessment. • The patient has received any investigational medication within 30 days prior to administration of trial medication or is scheduled to receive an in-vestigational drug up to 30 days after end of trial • The patient was previously admitted to this trial or simultaneous participa-tion in another clinical trial or participation in any clinical trial involving an administration of investigational medicinal product within 30 days prior to clinical trial beginning.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To establish a patient orientated endpoint “time to recovery from acute symptoms of acute vestibular neuritis” for phase III trials and to demonstrate faster recovery after betahistine treatment compared to placebo. (Key secondary objective) To analyze whether superiority of betahistine treatment is kept up to the end of treatment. To quantitatively describe/compare recovery over time vs. placebo and to determine optimal treatment duration. To shed light on the underlying mechanisms (i. e. peripheral vs. central compensation). To check for the occurrence of the adverse effects reported in the summary of medical product characteristics (SmPC) on the drug. ;Primary end point(s): "Total sway path" (length per time) on a compliant foam-padded posturography platform for postural control, and peak slow phase velocity of the spontaneous nystagmus. Measurements at day 10 (medium-term) and day 3 (short-term) after randomization (which is expected to be close to symptom onset). ;Timepoint(s) of evaluation of this end point: Measurements at day 10 (medium-term) and day 3 (short-term) after randomization (which is expected to be close to symptom onset). ;Main Objective: To demonstrate medium-term and short-term superiority of betahistine treatment regarding recovery of postural control or spontaneous nystagmus as compared to placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time in days from randomization to subjective recovery from acute symptoms of acute vestibular neuritis. (Key secondary endpoint) "Total sway path" (length per time) on a compliant foam-padded posturography platform for postural control with the eyes closed. Peak slow phase velocity of spontaneous nystagmus without visual fixation obtained from eye-movement recordings 10-40 sec in duration measured on day 28 after randomization (which is expected to be close to symptom onset) • "Subjective visual vertical" • Slow phase velocity of nystagmus provoked by caloric irrigation as a measure of peripheral vestibular function • Handicap / impairment due to vertigo or dizziness - assessed by the Dizziness Handicap Inventory and the Vestibular Disorders Activities of Daily Living score; these parameters will be measured on days 1, 3, 10, and 28 after randomization and • All these parameters 8 weeks after randomization.;Timepoint(s) of evaluation of this end point: Parameters will be measured on days 1, 3, 10, and 28 after randomization and 8 weeks after randomization. | — |
Countries
Germany
Contacts
Public ContactDSGZ
Hospital of the University of Munich
Outcome results
None listed