Meniere's Disease
Conditions
Keywords
Meniere's disease, transtympanic steroids, Randomised controlled trial
Brief summary
This trial aims to compare transtympanic steroids against the standard treatment (transtympanic gentamicin) in refractory unilateral Meniere's disease.
Detailed description
Meniere's disease is characterised by episodic spontaneous vertigo attacks with hearing loss, ringing sounds and fullness in the ear. In one out of five patients, standard first line medical treatment is not effective in controlling vertigo attacks. For these incapacitated patients, gentamicin injections through the ear drum is a well established minimally invasive treatment. Major surgery of the balance organs or nerve, risking complete hearing loss, CSF leak, meningeal infections, are rarely performed nowadays. Gentamicn is very effective in controlling vertigo and acts by chemical ablation of end organs. As hearing and balance organs are entwined around each other, gentamicin treatment does not come without the risk of hearing loss. In fact, meta-analysis shows hearing deterioration in 13% to 35% percent of gentamicin treated patients. On the other hand, steroids are drug of choice for autoimmune inner ear disease and commonly used for sudden hearing loss. They are non toxic drugs without any known side effects during local treatment in ear. We will compare the two in this randomised, double blind trial.
Interventions
DRUGMethylprednisolone
2 transtympanic injections at interval of two weeks.
DRUGGentamicin
2 transtympanic injections at an interval of two weeks. If there is significant hearing loss before second injection, it will be replaced by normal saline in double blinded fashion.
Sponsors
Imperial College Healthcare NHS Trust
Medical Research Council
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients with unilateral Ménière's disease (definite or probable, according to Committee on Hearing and Equilibrium guidelines, 1995) with hearing loss and presenting with recurrent vertigo, not responding to medical treatment for at least 6 months will be included. There should be normal, age appropriate hearing in the contralateral ear.
Exclusion criteria
* Patients with Ménière's disease in later stages (not having vertigo attacks). * Age: patients older than 70 years at the start of the trial. * Severe disability (e.g. neurological, orthopaedic, cardiovascular) or serious concurrent illness that might interfere with treatment or follow up. * Active additional neuro-otological disorders that may mimic Ménière's disease (e.g. vestibular migraine, vertebro-basilar TIAs, acoustic neuroma) and thus will make the objective follow up difficult. * Concurrent ear pathology that may interfere with transtympanic treatment (e.g. active middle ear disease). * Family history of unexplained deafness (possibility of genetic susceptibility to gentamicin toxicity). * History of known adverse/allergic reaction to steroids or gentamicin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vertigo Attacks | 6month pre-enrollment baseline, 18-24 months after initial treatment | The number of vertigo attacks between 18-24months follow-up were taken retrospectively during a face-to-face appointment at 24 months follow-up and compared to 6 month pre-enrollment baseline (as per Committee on Hearing and Equilibrium guidelines). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hearing | Baseline, 1,2,6,12,18 and 24months after initial treatment | Hearing was measured as ipsilesional pure-tone threshold at Baseline, 1month, 2months, 6months, 12month, 18months and 24 months follow-up. Hearing level was taken as the average threshold across 0.5, 1, 2 and 3KHz. |
| Change in Speech Discrimination | Baseline, 1,2,6,12 and 24months after initial treatment | Speech discrimination was measured at Baseline, 1month, 2months, 6months, 12month and 24 months follow-up. Speech discrimination was assessed by means of ipsilesional suprathreshold word recognition (%). Arthur Boothroyd's isophonemic word lists (AB wordlists, Guymark, Southampton) comprising sets of 10 words were played to the ipsilesional ear at the low-frequency pure-tone threshold of 0·5, 1 and 2 kHz +30dB with masking sound in the contralesional ear if necessary. The formula for masking level was: low-frequency pure-tone threshold in ipsilesional ear - bone conduction mean threshold (0·5, 1 and 2KHz) in contralesional ear - 40dB. Speech loudness and masking were rounded to the nearest 5dB. Step increments and decrements of 10dB for speech loudness and masking were used to attain the maximum speech discrimination score. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Steroid (Methylprednisolone) Methylprednisolone: 2 transtympanic injections at interval of two weeks. | 30 |
| Gentamicin Gentamicin: 2 transtympanic injections at an interval of two weeks. If there is significant hearing loss before second injection, it will be replaced by normal saline in double blinded fashion. | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Gentamicin | Steroid (Methylprednisolone) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 25 Participants | 50 Participants |
| Age, Continuous | 53.3 Years STANDARD_DEVIATION 10.8 | 51.6 Years STANDARD_DEVIATION 10.2 | 52.5 Years STANDARD_DEVIATION 10.5 |
| Region of Enrollment United Kingdom | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 15 Participants | 10 Participants | 25 Participants |
| Sex: Female, Male Male | 15 Participants | 20 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 32 |
| other Total, other adverse events | 3 / 30 | 3 / 32 |
| serious Total, serious adverse events | 0 / 30 | 0 / 32 |
Outcome results
Primary
Vertigo Attacks
The number of vertigo attacks between 18-24months follow-up were taken retrospectively during a face-to-face appointment at 24 months follow-up and compared to 6 month pre-enrollment baseline (as per Committee on Hearing and Equilibrium guidelines).
Time frame: 6month pre-enrollment baseline, 18-24 months after initial treatment
Population: Intention-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Steroid (Methylprednisolone) | Vertigo Attacks | 18-24months | 1.6 Vertigo Attacks | Standard Deviation 3.4 |
| Steroid (Methylprednisolone) | Vertigo Attacks | Baseline | 16.4 Vertigo Attacks | Standard Deviation 12.45 |
| Gentamicin | Vertigo Attacks | Baseline | 19.93 Vertigo Attacks | Standard Deviation 16.7 |
| Gentamicin | Vertigo Attacks | 18-24months | 2.5 Vertigo Attacks | Standard Deviation 5.8 |
p-value: 0.271ANOVA
Secondary
Change in Hearing
Hearing was measured as ipsilesional pure-tone threshold at Baseline, 1month, 2months, 6months, 12month, 18months and 24 months follow-up. Hearing level was taken as the average threshold across 0.5, 1, 2 and 3KHz.
Time frame: Baseline, 1,2,6,12,18 and 24months after initial treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Steroid (Methylprednisolone) | Change in Hearing | 2months | 49.83 dB | Standard Deviation 22.31 |
| Steroid (Methylprednisolone) | Change in Hearing | 12months | 47.02 dB | Standard Deviation 23.96 |
| Steroid (Methylprednisolone) | Change in Hearing | 1month | 49.29 dB | Standard Deviation 22.23 |
| Steroid (Methylprednisolone) | Change in Hearing | 18months | 48.44 dB | Standard Deviation 22.1 |
| Steroid (Methylprednisolone) | Change in Hearing | 6months | 46.67 dB | Standard Deviation 23.29 |
| Steroid (Methylprednisolone) | Change in Hearing | 24months | 46.9 dB | Standard Deviation 24 |
| Steroid (Methylprednisolone) | Change in Hearing | Baseline | 53.25 dB | Standard Deviation 21.17 |
| Gentamicin | Change in Hearing | 24months | 49.1 dB | Standard Deviation 18.1 |
| Gentamicin | Change in Hearing | Baseline | 51.5 dB | Standard Deviation 11.29 |
| Gentamicin | Change in Hearing | 1month | 52.18 dB | Standard Deviation 15.77 |
| Gentamicin | Change in Hearing | 2months | 48.99 dB | Standard Deviation 16.9 |
| Gentamicin | Change in Hearing | 6months | 45.48 dB | Standard Deviation 17.7 |
| Gentamicin | Change in Hearing | 12months | 47.34 dB | Standard Deviation 19.2 |
| Gentamicin | Change in Hearing | 18months | 44.82 dB | Standard Deviation 18.8 |
p-value: 0.964ANOVA
Secondary
Change in Speech Discrimination
Speech discrimination was measured at Baseline, 1month, 2months, 6months, 12month and 24 months follow-up. Speech discrimination was assessed by means of ipsilesional suprathreshold word recognition (%). Arthur Boothroyd's isophonemic word lists (AB wordlists, Guymark, Southampton) comprising sets of 10 words were played to the ipsilesional ear at the low-frequency pure-tone threshold of 0·5, 1 and 2 kHz +30dB with masking sound in the contralesional ear if necessary. The formula for masking level was: low-frequency pure-tone threshold in ipsilesional ear - bone conduction mean threshold (0·5, 1 and 2KHz) in contralesional ear - 40dB. Speech loudness and masking were rounded to the nearest 5dB. Step increments and decrements of 10dB for speech loudness and masking were used to attain the maximum speech discrimination score.
Time frame: Baseline, 1,2,6,12 and 24months after initial treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Steroid (Methylprednisolone) | Change in Speech Discrimination | Baseline | 64.97 Percentage correct | Standard Deviation 29.28 |
| Steroid (Methylprednisolone) | Change in Speech Discrimination | 1month | 71.78 Percentage correct | Standard Deviation 26.48 |
| Steroid (Methylprednisolone) | Change in Speech Discrimination | 2months | 76.10 Percentage correct | Standard Deviation 24.43 |
| Steroid (Methylprednisolone) | Change in Speech Discrimination | 6months | 75.63 Percentage correct | Standard Deviation 26.39 |
| Steroid (Methylprednisolone) | Change in Speech Discrimination | 12months | 73.43 Percentage correct | Standard Deviation 27.16 |
| Steroid (Methylprednisolone) | Change in Speech Discrimination | 24months | 76.32 Percentage correct | Standard Deviation 29.36 |
| Gentamicin | Change in Speech Discrimination | 12months | 71.58 Percentage correct | Standard Deviation 24.69 |
| Gentamicin | Change in Speech Discrimination | Baseline | 72.10 Percentage correct | Standard Deviation 21.67 |
| Gentamicin | Change in Speech Discrimination | 6months | 76.35 Percentage correct | Standard Deviation 25.92 |
| Gentamicin | Change in Speech Discrimination | 1month | 69.43 Percentage correct | Standard Deviation 22.94 |
| Gentamicin | Change in Speech Discrimination | 24months | 64.99 Percentage correct | Standard Deviation 30.75 |
| Gentamicin | Change in Speech Discrimination | 2months | 74.31 Percentage correct | Standard Deviation 23.4 |
p-value: 0.128ANOVA