Probiotic in Dry Eye Syndromes

Efficacy and Safety of Systemic and Ophthalmic Probiotic on Microbiota, Immunological and Clinical Outcomes of Patients With Dry Eye Syndrome

This study will evaluate efficacy and safety of systemic and ophthalmic probiotic from bacterial lysate of Lactobacillus sakei on microbiota, immunological and clinical outcomes of patients with Dry Eye Syndrome.

Study Overview

• Status: Completed
• Conditions: Dry Eye Syndrome
• Intervention / Treatment: Drug: Ophthalmic Probiotic; Dietary supplement: Oral Placebo Capsule; Drug: Opthalmic Placebo; Dietary supplement: Oral Probiotic Capsule

Detailed Description

The ocular surface is comprised of the cornea and its overlying tissue, the conjunctiva. The ocular surface is continuously exposed to the external environment and, therefore, to different microbial species. A resident ocular surface microbiota has been found in various studies. Although little is known so far, some elements of this microbiota and/or its metabolites could represent protective cofactosr in the pathogenesis of common ocular diseases.

On the other hand, the gut microbiota is known to influence host homeostasis in distal tissues, such as brain (gut-barin axis), lungs (gut-lungs axis) and skin (gut-skin axis). However, little is known about distal effects of the gut microbiota on the ocular surface.

In this study we sought to evaluate the efficacy and safety aspects of L.sakei as both ophtalmic probiotic lysate and oral live probiotic on Dry Eye Syndrome, using a factorial design, against placebo.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Fars
    • Shiraz, Fars, Iran, Islamic Republic of
      • Research Center for Traditional Medicine and History of Medicine-Shiraz University of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female
• 18<age<60
• BCVA (Best Corrected Visual Acuity) >=9/10
• At least 2 subjective complaints compatible with dry eye
• TBUT (Tear Break-Up Time) <= 10 sec, Schirmer's test <= 10mm
• Signed informed consent, voluntary adherence to treatment

Exclusion Criteria:

• Pregnancy/breastfeeding
• Conjunctivitis
• Thyroid disease
• Diabetes
• Rheumatologic diseases including Sjogren's syndrome
• Neurologic conditions, including stroke, Bell's palsy, Parkinson's, trigeminal nerve problem
• Refractive surgery (LASIK or PRK)
• Other Eye Surgeries
• HSV Keratitis
• Medication/supplement use, including psychiatric medicines, OTC cold medicines, anti-histamines, beta-blockers, pain relievers, sleeping pills, diuretics, Hormones replacement, and oral contraceptives
• Chemical splashes / injuries to the eyes
• Contact lens use
• Environmental (dusty, windy, hot/dry)
• Any treatment for dry eye in previous 4 weeks (including lubricants, steroids, cyclosporine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ophthalmic probiotic; 1 active drop in each eye/ 5 hours plus oral placebo capsule, for 4 weeks	Drug: Ophthalmic Probiotic; Bacterial lysate of Lactobacillus sakei, hydroxypropylmethylcellulose (HPMC), boric acid, sodium chloride, purified water.; Dietary supplement: Oral Placebo Capsule; Hydroxypropylmethylcellulose hard capsule, filled with maltodextrin excipient
Placebo Comparator: Placebo; 1 placebo drop in each eye/ 5 hours plus oral placebo capsule, for 4 weeks	Dietary supplement: Oral Placebo Capsule; Hydroxypropylmethylcellulose hard capsule, filled with maltodextrin excipient; Drug: Opthalmic Placebo; Placebo contains complete formulation of the active drug except for bacterial lysate of Lactobacillus sakei (i.e. HPMC, boric acid, sodium chloride, purified water)
Experimental: Opthalmic Probiotic + Oral Probiotic; 1 active drop in each eye/ 5 hours plus oral probiotic capsule, for 4 weeks	Drug: Ophthalmic Probiotic; Bacterial lysate of Lactobacillus sakei, hydroxypropylmethylcellulose (HPMC), boric acid, sodium chloride, purified water.; Dietary supplement: Oral Probiotic Capsule; Live Lactobacillus sakei (5 billion cfus) in hydroxypropylmethylcellulose hard capsule, with maltodextrin excipient
Experimental: Oral Probiotic; 1 placebo drop in each eye/ 5 hours plus oral probiotic capsule, for 4 weeks	Drug: Opthalmic Placebo; Placebo contains complete formulation of the active drug except for bacterial lysate of Lactobacillus sakei (i.e. HPMC, boric acid, sodium chloride, purified water); Dietary supplement: Oral Probiotic Capsule; Live Lactobacillus sakei (5 billion cfus) in hydroxypropylmethylcellulose hard capsule, with maltodextrin excipient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ocular Surface Disease Index	Subjective score	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tear break up time (TBUT)	Slit exam	4 weeks
Schirmer test	physical exam using Schirmer strip	4 weeks
Ocular surface microbiota composition	measured by 16s rRNA method	4 weeks
Tear Interleukin level	measured by ELISA	4 weeks

Collaborators and Investigators

• Sponsor: Shiraz University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): July 30, 2022

Study Registration Dates

• First Submitted: June 22, 2021
• First Submitted That Met QC Criteria: June 22, 2021
• First Posted (Actual): June 25, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 24, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Disease; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Syndrome; Dry Eye Syndromes; Keratoconjunctivitis Sicca
• Other Study ID Numbers: 97-01-104-18912

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No