Omega-3-Based Nutraceutical Supplementation as Adjunctive Therapy in Adults With Otitis Media With Effusion: A Multicenter, Double-Blind, Randomized Placebo-Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 501
- 试验地点
- 1
- 主要终点
- Tympanometric resolution
研究概览
简要总结
Brief Summary - OMENUTS Trial Otitis media with effusion (OME) is a condition in which fluid accumulates in the middle ear, causing conductive hearing loss, ear fullness, tinnitus, and Eustachian tube dysfunction. Although OME is well-recognized in children, it also affects adults, in whom it is frequently under-diagnosed and inadequately treated. No established, well-tolerated pharmacological therapy currently exists for adult OME, and current medical management options - including antihistamines, corticosteroids, and mucolytics - have shown inconsistent efficacy in clinical trials.
Omega-3 polyunsaturated fatty acids and associated nutraceutical compounds have well-documented anti-inflammatory and immunomodulatory properties that are mechanistically relevant to the pathophysiology of OME, which is driven by chronic low-grade mucosal inflammation, Eustachian tube dysfunction, and impaired mucociliary clearance. A nutraceutical combination containing omega-3 fatty acids, Spirulina, magnesium, and vitamin B6 has previously demonstrated efficacy in reducing inflammatory biomarkers and improving clinical outcomes in allergic rhinitis - a condition sharing key pathophysiological features with OME.
The OMENUTS trial is a multicenter, double-blind, randomized placebo-controlled trial designed to evaluate the efficacy of this nutraceutical combination as adjunctive therapy in adults with confirmed OME. The trial is conducted across three tertiary referral centres in Italy: Isola Tiberina - Gemelli Isola Hospital (Rome), the University of Catanzaro (Catanzaro), and Tortorella Clinic (Salerno).
A total of 501 adult participants aged 18 to 70 years with a confirmed diagnosis of OME - established by otoscopic examination and tympanometry (type B curve) of at least 4 weeks' duration - are randomized in a 1:1:1 ratio to one of three groups. All participants receive a shared background therapy of intranasal mometasone furoate spray and oral deflazacort for three weeks. In addition to the background therapy, participants in Group 1 (intervention group) receive the nutraceutical combination (omega-3 fatty acids, Spirulina, magnesium, and vitamin B6; one tablet daily) for three weeks; participants in Group 2 (active control group) receive oral bilastine 20 mg daily for three weeks; and participants in Group 3 (placebo group) receive an identical placebo tablet daily for three weeks.
The co-primary outcomes are tympanometric resolution - defined as normalization of the tympanometric curve from type B to type A - and audiometric improvement - defined as a reduction in pure-tone average of more than 15 dB HL - both assessed at the end of treatment (week 3, T1). Secondary outcomes include changes in patient-reported symptom severity (VAS), Eustachian tube dysfunction symptoms (ETDQ-7), psychosocial impact of hearing impairment (HHIA), and Eustachian tube patency assessed by the Valsalva maneuver. A 60-day post-treatment follow-up visit (T2) is included to evaluate recurrence rates across groups.
Randomization is computer-generated via REDCap, stratified by site, and implemented with permuted blocks of variable size. The trial is conducted under a double-blind design, with all investigational products identical in appearance, odour, and taste. Safety outcomes, including the incidence and nature of adverse events classified according to MedDRA criteria, are monitored continuously throughout the study.
The primary analysis is conducted on a modified intention-to-treat basis, including all participants who received at least one dose of the assigned treatment and completed at least one post-baseline assessment. The trial is conducted in accordance with the Declaration of Helsinki, CONSORT guidelines, and was approved by the Institutional Review Board of the Region of Calabria, Italy (approval code: 177/2026).
详细描述
Detailed Description - OMENUTS Trial
BACKGROUND AND RATIONALE Otitis media with effusion (OME) is defined as the presence of fluid in the middle ear cavity without signs or symptoms of acute infection. It is a leading cause of conductive hearing loss and represents one of the most prevalent conditions in paediatric otolaryngology, affecting up to 90% of children by age 10. Although considerably less prevalent in adults, OME in the adult population represents a clinically relevant and frequently under-investigated entity, estimated to affect approximately 3.2% of adults presenting with conductive hearing impairment. In adults, OME is more frequently associated with Eustachian tube dysfunction, chronic rhinosinusitis, and allergic inflammation rather than adenoidal hypertrophy, and its clinical presentation - including ear fullness, conductive hearing loss, tinnitus, and impaired Eustachian tube patency - can significantly affect quality of life and psychosocial functioning.
The pathophysiology of OME is multifactorial and incompletely understood. Eustachian tube dysfunction, impaired mucociliary clearance, and persistent low-grade inflammatory activity of the middle ear and nasopharyngeal mucosa are considered the principal underlying mechanisms, further perpetuated by factors such as allergic sensitization, viral upper respiratory infections, and biofilm formation. The chronic inflammatory component of OME pathogenesis - involving NF-κB-mediated cytokine production, mast cell activation, histamine release, and impaired resolution of inflammation - provides a mechanistically coherent rationale for the use of anti-inflammatory nutraceutical compounds as adjunctive therapy.
Management strategies for adult OME remain heterogeneous and controversial. Watchful waiting is recommended for uncomplicated cases, while surgical intervention - tympanostomy tube placement, with or without adenoidectomy - is reserved for chronic or symptomatic disease. Medical therapy, including antibiotics, corticosteroids, antihistamines, and mucolytics, has shown inconsistent efficacy in clinical trials. Antihistamines in particular have been shown to be ineffective in treating OME and may prolong effusion duration. No well-tolerated pharmacological option is currently established for adult patients, representing a significant unmet clinical need.
Omega-3 polyunsaturated fatty acids (PUFAs) - particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) - exert well-characterised anti-inflammatory effects through multiple pathways, including inhibition of NF-κB-mediated cytokine transcription, reduction of prostaglandin E2 and leukotriene B4 synthesis, and generation of specialised pro-resolving mediators including resolvins and protectins. Omega-3 fatty acids have also been shown to modulate inflammatory pathways through nutrigenomic mechanisms that influence the expression of cytokine-encoding genes, and dietary omega-3 supplementation has been shown to dampen allergic inflammation in the upper respiratory tract through eosinophilic production of 15-hydroxyeicosapentaenoic acid, a metabolite of EPA that inhibits mast cell degranulation via peroxisome proliferator-activated receptor gamma. DHA may additionally play a protective role in auditory neural conduction, with high plasma omega-3 concentrations associated with reduced hearing impairment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 70 years
- •Confirmed diagnosis of unilateral or bilateral otitis media with effusion (OME), established by otoscopic examination and tympanometry (type B curve)
- •Duration of symptoms of at least 4 weeks prior to enrollment
- •Ability to provide written informed consent
- •Willingness to comply with the study protocol and attend all scheduled visits
排除标准
- •Pregnancy or breastfeeding Uncontrolled asthma Chronic obstructive or restrictive pulmonary disease Autoimmune or connective tissue disease Acute sinusitis or acute upper respiratory tract infection at the time of enrollment Cardiovascular, hepatic, or renal disease Use of medications known to affect immune response History of nasal or sinus surgery Receipt of immunotherapy within 3 years prior to enrollment or planned immunotherapy during the study period Any other condition that, in the investigator's judgement, would preclude safe participation or compromise the integrity of the trial
结局指标
主要结局
Tympanometric resolution
时间窗: Week 3 (end of treatment, T1)
Description: Proportion of participants achieving complete tympanometric resolution, defined as normalization of the tympanometric curve from type B to type A, assessed by standard tympanometry. Reported as number and percentage of participants achieving resolution in each group, with between-group comparisons by Chi-square test and odds ratios with 95% confidence intervals.
Audiometric improvement
时间窗: Week 3 (end of treatment, T1)
Description: Proportion of participants achieving a reduction in pure-tone average (PTA) of more than 15 dB hearing level (HL) at the affected frequencies, assessed by pure-tone audiometry. Reported as number and percentage of participants achieving the threshold in each group, with between-group comparisons by Chi-square test and odds ratios with 95% confidence intervals.
次要结局
- Visual Analogue Scale (VAS) score(Baseline (T0), Week 3 (T1), Day 60 post-treatment (T2))
- Eustachian Tube Dysfunction Questionnaire (ETDQ-7) score(Change in psychosocial impact of hearing impairment from baseline, assessed using the validated 25-item Hearing Handicap Inventory for Adults (HHIA), yielding a total score ranging from 0 to 100, where higher scores indicate greater perceived handicap. T)
- Eustachian tube patency (Valsalva maneuver)(Baseline (T0), Week 3 (T1), Day 60 post-treatment (T2))
- Recurrence rate(Proportion of participants with recurrence of OME at the 60-day post-treatment follow-up visit, defined as re-emergence of a type B tympanogram in patients who had achieved type A tympanometric resolution at T1. Between-group comparisons by Chi-square te)
- Treatment adherence(Week 3 (T1))
研究者
Pietro De Luca
MD
Isola Tiberina - Gemelli Isola Hospital, Rome, Italy