A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial Evaluating the Efficacy and Safety of a Microbiome-Focused Oral Food Supplement in Adults With Moderate Evaporative Dry Eye Disease Associated With Meibomian Gland Dysfunction
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 130
- 试验地点
- 3
- 主要终点
- Change from baseline in Ocular Surface Disease Index-6 (OSDI-6) total score
研究概览
简要总结
Dry eye disease (DED) is a common chronic condition characterized by ocular surface discomfort and tear film instability. Evaporative DED associated with meibomian gland dysfunction (MGD) is a frequent phenotype and is often driven by inflammatory mechanisms. This randomized, double-blind, placebo-controlled trial evaluates whether an oral microbiome-focused food supplement improves dry eye symptoms and objective clinical signs compared with placebo over 8 weeks in adults with moderate evaporative DED due to MGD.
详细描述
Participants with moderate evaporative DED associated with MGD will be randomized 1:1 to receive either a microbiome-focused oral food supplement or matching placebo for 8 weeks. The primary endpoint is change in Ocular Surface Disease Index (OSDI) from baseline to Week 8 and at 16 week follow-up. Key secondary endpoints include changes in tear film breakup time (TBUT), Schirmer I test, and ocular surface staining. Safety and tolerability will be assessed throughout the study. Standard supportive care (e.g., preservative-free artificial tears) will be permitted if kept stable and documented.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Incluison criteria:
- •Adults aged 18-65 years.
- •Participants were required to meet all of the following criteria:
- •Presence of dry eye symptoms, defined as an OSDI-6 summed score ≥4 at baseline.
- •Objective evidence of tear film homeostasis loss in at least one eye, defined by at least one of the following:
- •A: Non-invasive tear break-up time (NIBUT) <10 seconds, and/or
- •B: Ocular surface fluorescein staining consistent with DED, defined as:
- •Corneal and/or conjunctival fluorescein staining graded ≥1 using the Oxford scale, and/or
- •Lid wiper epitheliopathy graded ≥1 using the Korb grading system
- •Ability to provide written informed consent and comply with study procedures.
- •Willingness to maintain stable use of permitted background measures (e.g., preservative-free artificial tears) and to avoid initiating new probiotics/prebiotics during the trial.
排除标准
- •Sjögren syndrome or other active systemic autoimmune disease with significant ocular involvement (investigator judgment).
- •Active ocular infection, acute blepharitis flare, or active allergic conjunctivitis requiring escalation of therapy.
- •Ocular surgery (including cataract) or significant ocular trauma within 6 months prior to the Screening Visit.
- •Previous LASIK or any prior corneal surgery at any time.
- •Use of topical cyclosporine, lifitegrast, or topical ocular corticosteroids within 6-8 weeks prior to baseline, or planned initiation during the treatment period.
- •Punctal plugs within 3 months prior to baseline or planned during the study.
- •Use of glaucoma medications or history of glaucoma filtering surgery.
- •Contact lens use within 30 days prior to baseline or planned use during the study.
- •Systemic isotretinoin within 6 months prior to baseline.
- •Systemic antibiotic use within 8 weeks prior to baseline.
- •Eyelid abnormalities affecting lid function (e.g., lagophthalmos, blepharospasm, ectropion, entropion, severe trichiasis).
- •Active thyroid eye disease (thyroid orbitopathy) or clinically significant ocular surface exposure secondary to thyroid dysfunction.
- •Extensive ocular surface scarring or conditions compromising ocular surface integrity, including Stevens-Johnson syndrome, prior chemical burn, recurrent corneal erosions, persistent epithelial defects, or prior severe ocular trauma.
- •Known hypersensitivity to study product ingredients.
- •Any medical or ocular condition that, in the investigator's opinion, would compromise patient safety or study integrity.
- •Pregnancy or breastfeeding (if applicable) or planning pregnancy during the intervention period.
- •Gastrointestinal diseases known to significantly affect digestion, absorption, or intestinal physiology, including but not limited to inflammatory bowel disease, celiac disease, or a history of major gastrointestinal surgery
- •Individuals following restrictive or specialized dietary patterns, including ketogenic, vegan, or similar diets
研究组 & 干预措施
Microbiome-targeted oral food supplement
Oral food-grade supplement designed to modulate gut microbiome-linked metabolic pathways relevant to ocular surface homeostasis (gut-eye axis). Administered once daily for 8 weeks (e.g., sachet/capsule taken with water). Packaging and appearance are matched to placebo.
干预措施: Dietary Supplement: Microbiome-targeted oral supplement (Dietary Supplement)
Placebo Comparator
Participants receive a matched placebo once daily for 8 weeks, plus permitted background dry eye care.
干预措施: Placebo (Other)
结局指标
主要结局
Change from baseline in Ocular Surface Disease Index-6 (OSDI-6) total score
时间窗: Baseline to Week 8 (end of treatment)
The Ocular Surface Disease Index-6 (OSDI-6) is a shortened 6-item patient-reported outcome measure recommended by TFOS DEWS III as the standardized screening questionnaire for dry eye disease. Each item is scored from 0 to 4, and the total score is calculated as the sum of the 6 item scores, yielding a total score range of 0 to 24. Higher scores indicate worse dry eye symptom burden. According to TFOS DEWS III, OSDI-6 scores may be interpreted as follows: 0-3, normal range; 4-8, mild-to-moderate symptom severity; and \>8, severe symptom severity. A score of 4 or higher is considered consistent with a positive symptom screen for dry eye disease. The primary endpoint is the mean change from baseline in OSDI-6 total score at Week 8, corresponding to the end of the intervention period.
Change from baseline in Ocular Surface Disease Index (OSDI) total score
时间窗: Baseline to Week 8 (end of treatment)
The OSDI is a validated 12-item patient-reported outcome assessing dry eye symptoms and vision-related function. Total score ranges from 0 to 100, with higher scores indicating worse symptoms. The primary endpoint is the mean change from baseline in OSDI total score at end of treatment.
OSDI Responder Rate at Week 8
时间窗: Baseline to Week 8
Proportion of participants achieving a clinically meaningful improvement (e.g., ≥10-point decrease in OSDI from baseline).
次要结局
- Change from baseline in Ocular Surface Disease Index-6 (OSDI-6) total score (durability)(Baseline to Week 16)
- Change in gut microbiome alpha diversity (e.g., Shannon index)(Baseline to Week 8)
- Change from baseline in Ocular Surface Disease Index (OSDI) total score (durability)(Baseline to Week 16)
- Change from baseline in Non-Invasive Break-Up Time (NIBUT)(Baseline to Week 8 and Baseline to Week 16)
- Change from baseline in conjunctival staining score (Oxford grading scheme)(Baseline to Week 8 and Baseline to Week 16)
- Change from baseline in rescue artificial tear use (drops/day)(Baseline to Week 8 (end of treatment) and Baseline to Week 16 (8 weeks post-treatment))
- Change from baseline in meibomian gland dropout score (meibography; SIRIUS)(Baseline to Week 8 (end of treatment) and Baseline to Week 16 (8 weeks post-treatment))
- Conjunctival redness severity (Efron grading scale)(Baseline (Week 0), Week 8 (End of Treatment), and Week 16 (Follow-up))
- Change from baseline in Schirmer I test without anesthesia (mm/5 min)(Baseline (Week 0), Week 8 (End of Treatment), and Week 16 (Follow-up))
- Incidence of adverse events (AEs) and serious adverse events (SAEs)(Baseline through Week 16 (8 weeks post-treatment))
- Change in gut microbiome beta diversity (Bray-Curtis distance)(Baseline to Week 8)
- Change from baseline in meibum quality score(Baseline to Week 8 and Baseline to Week 16)
- Change from baseline in meibomian gland expressibility score(Baseline to Week 8 and Baseline to Week 16)
研究者
Varol TUNALI
Supervisor
ENBIOSIS BIOTECHNOLOGIES