Clinical trial NCT06718452: Tinnitus and Treatment With umPEA-LUT
Official title: Treatment of Tinnitus Targeting Neuroinflammation. umPEALUT as Possible Option
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Tinnitus
Neuroinflammation
Keywords: Tinnitus
Neuroinflammation
Palmitoyetanolamide
Luteolin
Ultramicronized
Vascular
Central
Peripheral
Auditory cortex
Inner ear
Lead sponsor: University of Campania Luigi Vanvitelli
Sponsor class: OTHER
Collaborators: name: Universita degli Studi di Napoli Federico
First posted: 2024-12-05
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Longitudinal study
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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 and two (TREATMENT) groups that will use umPEALUT in different dosages. Group 1 will use the supplement 1 sachet/day every day, while group 2 will use 2 sachets of umPEALUT.

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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Tinnitus
timeFrame: At Enrollement, after 3 months of treatment, after 6 months of treatment (end of the therapy)
Secondary outcomes:
measure: Auditory test
timeFrame: Enrollement (T0) and after 6 months (end of the therapy)
Other outcomes:
Locations:
city: Naples
country: Italy
facility: Vanvitelli ENT department
state: Campania
Study officials:
affiliation: Vanvitelli University
name: Arianna Di Stadio, MD, PhD, MSc
role: STUDY_CHAIR
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