Meniere's disease: new treatments

New Treatments for Meniere's Disease

Timothy C. Hain, MD • Page last modified: May 13, 2021

In general, it is best to be very skeptical about new treatments for Meniere's. Because the disease fluctuates, very large numbers are needed to prove that a treatment is effective. In other words, one can easily by chance have a sequence of patients who do well on any particular regimen, medication or device, which is actually a placebo. There are many Meniere's treatments which are probably placebos. Considerable data supporting the placebo idea has been put forth by Torok (1977) and Ruckenstein (Ruckenstein et al. 1991). There is very little evidence that any currently available treatment, whether it be medical or surgical, changes hearing. (Am J Otol 18:67-73, 1997) There is good evidence, though, that certain destructive treatments (such as gentamicin) alleviate dizziness. Comments are in italics.

IT gentamicin protects the other ear (?) Wu and associates (2021) reported that hearing improved on the opposite side after ITG. This was a small study (of 30 patients). This unexpected effect is probably just an error related to an underpowered study. It is very difficult to understand why killing off part of the ear on the "bad" side should help the better ear. Mechanisms other than just a mistake are reduction of tinnitus (which might mask the other side), and reduction of the size of the "immune target". Just a mistake is the most likely cause however, and i needs to be checked in a larger group.
SPI-1005. A company called "Sound Pharmaceuticals" announced in a press release (also see local copy) dated Sept 18, 2019, that their experimental drug improved tinnitus and restored sensorineural hearing loss in patients affected by Meniere's disease. This was a study of about 160 subjects, evaluated with hearing tests and questionnaires. This is barely enough subjects when one is studying disorder like Meniere's that fluctuates so much. The main hearing outcome variable was low-tone hearing. Or in other words, this drugs does not seem to bring back dead ears to life again (i.e. the middle and high frequencies). Whether it helps dizziness is uncertain. We think the right attitude here is hope -- that this drug is proven to be helpful in larger studies.
Tenotomy of middle ear muscles. Roughly since 2003 (Franz et al), there have been suggestions that the tensor tympani muscle in the middle ear is involved with Meniere's attacks, with the hypothesis that contraction of this muscle increases inner ear pressure. This hypothesis is somewhat of the opposite of that held by the "Meniett" device, where there is an explicit attempt to increase middle ear pressure using the device. The holding of contractory theories is rather common in Meniere's research. Albu et al (2015) reported that tenotomy was more effective than endolymphatic shunt (probably a placebo), but "No significant difference in vertigo class was demonstrated:" De Valck et al (2009) reported "This preliminary study suggests no additional benefit of stapedius and tensor tympani tenotomy in the treatment of Meniere's disease patients", when comparing patients with both ITG (gentamicin) and ST. Overall, we think that there may be some small benefit to tenotomy in Meniere's, but because it is difficult to see how this procedure works, and also because of the lack of the possibility of a placebo controlled trial, we think it best to be very cautious about this treatment. Or to put this in another way, we would not recommend it for our patients, considering that low dose gentamicin works so well. One would think that if the proposed mechanism (increased inner ear pressure from stapedius) is accurate, SCD should be associated with a lower prevalence of Meniere's. No data is available to bring to bear on this.
Venous angioplasty. Attanasio et al (2019) reported mildly positive effects of "vascular intervention with bilateral percutaneous transluminal angioplasty (PTA) of the jugular/azygos veins" in 500+ patients with Meniere's disease. All measures were subjective, and the effect size on audiometry (which is a subjective measure as well) was small. We are dubious that it is possible to blind patients to angioplasty, and we are also dubious that any mechanical procedure will restore dead hair cells to life again. We think more studies are needed in other institutions, ideally using an objective outcome measure (perhaps imaging of hydrops).
Erectile dysfunction drugs. Degereman and associates (2017) recently published an article suggesting that drugs affecting phosphodiesterase (PDE), including sidenafil, can result in the development of endolymphatic hydrops. This was a mouse study with 28 days of continuous administration. We have never encountered a connection in our patients between ED drugs and Meniere's, but this report is disturbing.
Vestibular rehabilitation: Lack of evidence for helpfulness in Meniere's. "Conclusion Based on the low quality of the selected studies, it is inconclusive whether there is a positive effect of vestibular rehabilitation in patients with MD on balance and dizziness-related quality of life." The author's abstract says it all (Van Esch et al, 2017).
Steroid-gel (OTO-104). 8-1-2016 press release. Otonomy is in process of obtaining an FDA indication for use of a dexamethasone gel to treat Meniere's. Oto-104 is currently underoing two phase 3 trials. Comment: Here we have a company developing a treatment that requires injection of a gel containing steroids through the ear drum every 3 months. There are obvious issues with cost, ear drum perforation, and infection. It is puzzling to us why someone would wish to undergo repeated steroid injections through their ear drum when low dose gentamicin works very well, and requires a single injection only. As of 8/31/2017, Otonomy suspended development of this preparation, after it failed a late-stage trial.
Triple canal plugging. Zhang et al, 2016. In this puzzling paper, Zhang et al report plugging the semicircular canals, leaving the otoliths untouched, to treat Meniere's. This is puzzling as one would wonder why undertake invasive surgery when low dose gentamicin works very well, and why leave the otoliths untouched, when the otolithic crises are a major cause of disability in Meniere's.
Hyperbaric oxygen. Fattori et al, Audiology 35(6):322-34, 1996. These authors report the results of treatment for 15 days with 90 min. sessions of a pressure chamber. They report better hearing results in the treated patients. Comment: lacking a reasonable mechanism and also considering the general problems with placebo responses in Menieres (see the classic paper entitled Old and New in Menieres, by N. Torok), this treatment remains unsubstantiated.
Labyrinth anesthesia. (Adunka, Moustaklis et al. 2003) In this treatment, lidocaine and Kinetin are instilled into the middle ear using transtympanic injection. A remission was reported in 66% of patients. It is difficult to see why a local anesthetic that is gone in hours at most should cause a long lasting remission. Kinetin is a plant growth factor, pesticide, and an ingredient in skin preparations. Perhaps Kinetin has a positive effect on Meniere's disease.
Latanoprost. Rask-Andersen et al. (Otol HNS 2005, 133, 441-443). These authors report injections of this drug through the ear drum once/daily for 3 days. 9 patients were studied. They report improvements in vertigo (30%) and hearing. This drug, used for treatment of glaucoma, has been here tried in the ear. The apparent rationale is reduction of hydrops. This small study shows that it is feasible to use this drug. It is too small to say if it is truly useful.
Endolymphatic Duct Blockage. Saliba and others (2015) reported that EDB resulted in 96.5% complete control of vertigo spells, with no adverse effects. Comment: Sounds wonderful -- but we would like to see this result replicated. Similar procedures in animals result in the opposite effect -- induction of hydrops. In essence, this theory is the opposite of the central dogma of Meniere's regarding endolyphatic pressure. More data is certainly needed.
Water. In an amazing report, Naganuma and others from Japan (2006) studied 29 people and reported that large amounts of water intake taken over 2 years (35 ml/Kg -- or about 2.5 liters for a 70 kilo person), "dramatically relieved vertigo" and significantly improved hearing in the last 6 months. In our opinion, this study is underpowered (not enough subjects to prove their point), and also dangerous in that it may lead people to become water intoxicated. We see no reason why there should be good results only in the last 6 months, and also we don't think that a total of 29 patients is anywhere near enough. On the other hand, drinking sufficient water is recommended in current literature on Meniere's.
Antifungals. Leong et al recently published a retrospective study of 26 patients treated with oral mycostatin, an antifungal. Of course, this is an uncontrolled study, and subject to the usual problems of these studies in Meniere's disease (Leong, Pothie, Rutka 2014). While "hope springs eternal", this is pretty thin data. It is difficult to see why an antifungal that is confined to the intestinal tract would be helpful for Meniere's disease. Neely and Nelson (1994) published a similar paper in 1994.
Antivirals. Gacek (2015) reported that 12 of 31 patients had "complete control of vertigo" when treated with acyclovir or valacyclovir in large doses. This was an uncontrolled study that needs to be redone with a placebo control.
New diagnostic modalities:
Intratympanic gadolinium. Louza et al (2012) reported that intratympanic gadolinium had no short term effect on hearing. This study allows for the possibility of imaging the labyrinth using MRI. See also our page on using MRI to diagnose Meniere's.
shift-DPOAE. Quatre et al (2018) reported that "Abnormal EcochG and shift-DPOAEs in patients with definite Meniere's disease (DMD) were found in 68 and 64.5%, respectively." The shift corresponds to phase shift. We have not encountered this technique in other published work as of 2021.

References:

Adunka, O., E. Moustaklis, et al. (2003). "Labyrinth Anesthesia - A Forgotten but Practical Treatment Option in Meniere's Disease." ORL J Otorhinolaryngol Relat Spec 65(2): 84-90.
Attanasio G, Califano L Bruno A3, Giugliano V, Ralli M, Martellucci S, Milella C, de Vincentiis M Russo FY6, Greco A.Chronic cerebrospinal venous insufficiency and meni?re's disease: Interventional versus medical therapy. Laryngoscope. 2019 Nov 11. doi: 10.1002/lary.28389. [Epub ahead of print]
Degerman, E., et al. (2017). "Inhibition of phosphodiesterase 3, 4, and 5 induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4T MRI." Acta Otolaryngol 137(1): 8-15.
Gacek RR. . Recovery of Hearing in Meniere's Disease after Antiviral Treatment. .Am J Otolaryngol. 2015 May-Jun;36(3):315-23. doi: 10.1016/j.amjoto.2014.03.016. Epub 2014 Apr 5
Gates GA and others. The effects of transtympanic micropressure treatment in people with unilateral Meniere's disease. Arch Otol HNS 2004:130;718-725
Leong AC, Pothier DD, Rutka JA.Oral Mycostatin as a possible alternative treatment for intractable Ménière's disease: preliminary cohort study. J Laryngol Otol. 2014 Mar 19:1-2. [Epub ahead of print]
Louza JP, Flatz W, Krause E, Gürkov R.Short-term audiologic effect of intratympanic gadolinium contrast agent application in patients with Ménière disease. Am J Otolaryngol. 2012 Feb 6. [Epub ahead of print]
Naganuma H, Kawahara K, Tokumasu K, Okamoto M. Laryngoscope.Water may cure patients with meniere disease. 2006 Aug;116(8):1455-60.
Neely, J. G. and R. A. Nelson (1994). "Orally ingested nystatin powder in water for the stabilization of hearing in patients with fluctuating hearing loss." Otolaryngol Head Neck Surg 111(1): 1.
Quatre R, Attyé A, Karkas A, Job A, Dumas G, Schmerber S. Ear Hear. 2018 Apr 25. doi: 10.1097/AUD.0000000000000584. [Epub ahead of print] Relationship Between Audio-Vestibular Functional Tests and Inner Ear MRI in Meniere's Disease
Rask-Andersen et al. Effects of intratympanic injection of latanoprost in Meniere's disease: a randomized placebo-controlled, double-blind, pilot study. Otol HNS 2005, 133, 441-443
Ruckenstein MJ, Rutka JA and Hawke M (1991). "The treatment of Meniere's disease: Torok revisited." Laryngoscope 101(2): 211-8.
Saliba, I., et al. (2015). "Endolymphatic Duct Blockage: A Randomized Controlled Trial of a Novel Surgical Technique for Meniere's Disease Treatment." Otolaryngol Head Neck Surg 152(1): 122-129.
Torok N (1977). "Old and new in Meniere disease." Laryngoscope 87(11): 1870-7.
van Esch, B. F., et al. (2017). "The Effect of Vestibular Rehabilitation in Patients with Meniere's Disease." Otolaryngol Head Neck Surg 156(3): 426-434.
Wu, Y., et al., 2021. Intratympanic gentamicin injection for refractory ménière's disease (MD) has potential effect in preventing contralateral MD occurrence. Acta Oto-Laryngologica. 1-6. https://doi.org/10.1080/00016489.2021.1915499
Zhang D, Fan Z, Han Y, Lv Y, Li Y, Wang H.Triple semicircular canal plugging: a novel modality for the treatment of intractable Meniere's disease.Acta Otolaryngol. 2016 Jul 19:1-6. [Epub ahead of print]

References concerning middle ear tenotomy

Albu, S., et al. (2015). "Endolymphatic sac surgery versus tenotomy of the stapedius and tensor tympani muscles in the management of patients with unilateral definite Meniere's disease." Eur Arch Otorhinolaryngol 272(12): 3645-3650.
De Valck, C. F., et al. (2009). "Tenotomy of the tensor tympani and stapedius tendons in Meniere's disease." B-ENT 5(1): 1-6.
Franz, P., et al. (2003). "Do middle ear muscles trigger attacks of Meniere's disease?" Acta Otolaryngol 123(2): 133-137.