Tinnitus and Treatment With umPEA-LUT

Официальное название

Treatment of Tinnitus Targeting Neuroinflammation. umPEALUT as Possible Option

Обзор

Tinnitus can have different causes. From a peripheral point of view, the sensation of hearing a not present sound can be indicative of damage in the cells of the cochlea. Damage at this level can arise from traumatic, vascular, toxic origins or be caused by systemic pathologies. However, all the previous causes have a common denominator, the presence of reactive oxygen species (ROS), in the cochlea which determines the damage and the consequent death of the hair cells into the ear. The sound (tinnitus) that the patient perceives is generated by the spontaneous movement of the cilia of the hair cells; this phenomenon arises when these cells begin to be damaged. Tinnitus can be also caused by a retrocochlear disorder such as damage of the auditory nerve (inflammatory and tumor cause). In case of an inflammatory origin, the factors released during inflammation can locally damage the nerves and spread into the cochlea destroying the hair cells. Tinnitus can also originate from damage in the central auditory pathway. In this case, the problem persistent. It is important to keep in mind that although initially the tinnitus may originate from a damage inside the cochlea, after 6 months of persistence chronicizes causing an activation (without stimulus) of the upper auditory areas. This zone of "hypersensitivity" is therefore responsible for chronic tinnitus. In addition to the overmentioned medical causes, tinnitus can also be sign of psychiatric/psychological disorders, in those cases in whom there is an involvement of the hypothalamus, as showed by neuropsychological studies. Tinnitus can be temporary and disappear spontaneously or, in the most of cases, be persistent and extremely annoying/stressful for the patient. At night in particular, in the absence of noise, the patient suffers more the presence of this ghost sound, which in some occasions prevents sleep. Insomnia negatively impacts on tinnitus increasing its duration and intensity, thus establishing a perpetual cycle of stress into the brain. The latter phenomenon worses and chronicizes the symptom . Stress causes inflammation with ROS increase, which can affect both the peripheral and central auditory pathways. Recently, it has been shown that tinnitus can be a symptom of neuro-inflammatory pathologies such as, for example, Multiple Sclerosis. The effects of inflammation on the hair cells are identifiable only through electrophysiological studies or from the temporal bone. Keeping on mind inflammation and neuro-inflammation and considering the exchange between cerebrospinal fluid and perilymph , we speculate that the use of a molecule capable of reducing inflammation and modulating the action of mast cells and microglia, could be an effective tool to resolve tinnitus; moreover, thanks to its powerful action at the level of neuro-inflammation, it could reduce the hyper-activity in the upper auditory tracts, thus reducing/abolishing noise. umPeaLut combines palmitoylethanolamide, which modulates the activity of mast cells, macrophages and microglia and luteolin, a bioflanoid extracted from fruits with anti-oxidant properties, able to improve microcirculation. Because the alterations of the ear microcirculation can be an additional cause of tinnitus, we believe that luteolin content can be an ulterior benefit. Although various attempts have been made to use a mono-molecule, recent studies have shown that combination of several elements could reduce tinnitus ; PeaLut, in its ultra-micronized form with high bioavailability, could be the perfect solution. This study aims at evaluating the efficacy of umPEALUT as a therapeutic treatment of tinnitus in a sample of adults.

Подробное описание

Longitudinal study on 100 patients

Patients between 18 and 70 years of age, not affected by systemic disorders (hypertension, diabetes, neurological disorders, previous stroke) or known psychological/psychiatric disorders will be included.

The patients will be evaluated at three observation times: T0 before treatment at the time of enrollment, T3 after 3 months and T6 after six months of treatment.

All patients, at each check-point will be screened as following: 1) three questionnaire to evaluate Tinnitus and 2) audiometric examination and acuphenometry.

Patients will be randomized into three groups, one group (CONTROL) that will use placebo, one (TREATMENT1 ) group that will use umPEALUT 2 sachets for day, and the other group (TREATMENT 2) umPEALUT 2 sachets par day combined to 120 mg of Rutin and 100 of 5-hTP.

EXPECTED RESULTS

Patients treated with umPEALUT compared to the control group will present an improvement of the symptom due to the anti-ROS action of luteolin and the neuro-immuno-modulating action of PEA. However the combination of umPEALUt with rutin and 5hTp will have better results than treatment with umPEALUT alone and control.

The changes induced by the treatment will be identifiable through the improvement of the symptom (responses to the questionnaire) and the changes in the subjective auditory test.

Specifically, patients in group 1 will present better final values than group 2, although group 2 will, however, present improvements compared to the control.

Вмешательства

• Пищевая добавка PEA-LUT 2 sachet day
  1 sachet two times a day to be sublingually absorbed
• Пищевая добавка Placebo
  Same administration of PEA-LUT
• Комбинированный продукт umPEALUT + Rutin + 5 hTp
  People in this group will be treated by 2 sachets par day of umPEALUT associated to 120 mg of rutin and 100 mg of 5 hTp

Первичные конечные точки

• Tinnitus [Срок оценки: At Enrollement, after 3 months of treatment, after 6 months of treatment (end of the therapy)]

Вторичные конечные точки (1)

• Auditory test [Срок оценки: Enrollement (T0) and after 6 months (end of the therapy)]

Критерии участия

Критерии включения

\- Patients with tinnitus not under treatment at least for 30 days

Критерии исключения

• Stroke in the last year
• Uncontrolled diabetes,
• Uncontrolled hypertension,
• Severe psychiatric disorders,
• Severe cognitive decline,
• Previous surgery of the brain or audio-vestibular nerves

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Италия · 1 центр

• Vanvitelli ENT department — Naples

Публикации

• Polanski JF, Soares AD, de Mendonca Cruz OL. Antioxidant therapy in the elderly with tinnitus. Braz J Otorhinolaryngol. 2016 May-Jun;82(3):269-74. doi: 10.1016/j.bjorl.2015.04.016. Epub 2015 Oct 17. PMID 26547700
• Petridou AI, Zagora ET, Petridis P, Korres GS, Gazouli M, Xenelis I, Kyrodimos E, Kontothanasi G, Kaliora AC. The Effect of Antioxidant Supplementation in Patients with Tinnitus and Normal Hearing or Hearing Loss: A Randomized, Double-Blind, Placebo Controlled Trial. Nutrients. 2019 Dec 12;11(12):3037. doi: 10.3390/nu11123037. PMID 31842394
• Wicinski M, Socha M, Walczak M, Wodkiewicz E, Malinowski B, Rewerski S, Gorski K, Pawlak-Osinska K. Beneficial Effects of Resveratrol Administration-Focus on Potential Biochemical Mechanisms in Cardiovascular Conditions. Nutrients. 2018 Nov 21;10(11):1813. doi: 10.3390/nu10111813. PMID 30469326
• Facchinetti R, Valenza M, Bronzuoli MR, Menegoni G, Ratano P, Steardo L, Campolongo P, Scuderi C. Looking for a Treatment for the Early Stage of Alzheimer's Disease: Preclinical Evidence with Co-Ultramicronized Palmitoylethanolamide and Luteolin. Int J Mol Sci. 2020 May 27;21(11):3802. doi: 10.3390/ijms21113802. PMID 32471239
• Di Stadio A, Ralli M. Inner ear involvement in multiple sclerosis: An underestimated condition? Mult Scler. 2018 Aug;24(9):1264-1265. doi: 10.1177/1352458517750010. No abstract available. PMID 30015600
• Albanese M, Di Girolamo S, Silvani L, Ciaschi E, Chiaramonte B, Conti M, Passali FM, Di Gioia B, Mercuri NB, Di Stadio A. Distortion Product Otoacoustic Emissions and Their Suppression as Predictors of Peripheral Auditory Damage in Migraine: A Case-Control Study. J Clin Med. 2021 Oct 27;10(21):5007. doi: 10.3390/jcm10215007. PMID 34768526
• Cronlein T, Langguth B, Geisler P, Hajak G. Tinnitus and insomnia. Prog Brain Res. 2007;166:227-33. doi: 10.1016/S0079-6123(07)66021-X. PMID 17956787
• Mazurek B, Szczepek AJ, Hebert S. Stress and tinnitus. HNO. 2015 Apr;63(4):258-65. doi: 10.1007/s00106-014-2973-7. PMID 25862619

Идентификаторы

NCT: NCT06718452 · UniLINK2026 · University LINK

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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