Pseudomonal Type Three Secretion System and Contact Lens Associated Microbial Keratitis

NCT ID: NCT01925846

Last Updated: 2014-04-15

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 180 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2015-07-31

Brief Summary

Microbial infection of the cornea, also known as microbial keratitis, causes severe corneal inflammation that could result in permanent visual loss. Contact lens wear is the strongest risk factor related to microbial keratitis in developed countries. The most commonly isolated pathogen of contact lens associated microbial keratitis (CLMK) is Pseudomonas aeruginosa, which accounts for over one third of the cases. Among the various virulence factors involved in the pathogenesis of pseudomonal keratitis, a secretion system known as type three secretion system (T3SS) secretes toxins that damage the host cells. ExoS is a bifunctional exotoxin with GTPase-activating protein (GAP) activity and ADP ribosyl transferase (ADPRT) activity. It results in an invasive phenotype of P. aeruginosa causing a relatively slower host cell death with intracellular invasion and possibly proliferation of bacterium. In contrast, ExoU expressing strains carries a cytotoxic phenotype that causes rapid host cell lysis due to its phospholipase activity. Previously, cytotoxic strains were reported to be more commonly found in patients with pseudomonal keratitis and were highly correlated with multidrug resistance.

In order to understand the pathogenesis of CLMK, especially pseudomonal related CLMK, we proposed to recruit 180 volunteers who will wear different contact lens materials. We then collect the used contact lens and analyze 1) the microbiota on the used contact lens; 2) the bacterial-contact lens adhesion of wild strains, pscC mutant strains (T3SS needle-comples mutant), cytotoxic strain, and invasive strain P. aeruginosa; 3) the effect of shearing forces on bacterial-contact lens adhesion; 4) the bacteriocidal effect of multipurpose solution on different strains of P. aeruginosa.

Detailed Description

Subject recruitment

The inclusion criteria includes:

1. age 20-35 years old

2. myopia less than -6.00D and astigmatism less than -1.50D

3. previous soft contact lens wear discontinued for at least 2 weeks.

Exclusion criteria includes:

1. subjects with previous RGP wear

2. any ocular inflammation or infection, proved dry eye syndrome, glaucoma, ocular trauma or surgery, and topical medication instillation

3. diabetic mellitus

4. pregnancy

5. status post corneal refractive surgery

The aim and purpose of this study will be thoroughly explained to the potential participants. Informed consent will be obtained from all enrolled subjects. This study will be approved by our Institutional Review Board and adheres to the tenets of the Declaration of the Helsinki. A minimal of 12 subjects per group is required to show a difference in the microbiota for one classification level or more at a significance level of 0.05 and a power of 90%. Thus, the goal is to recruit 15 volunteers to wear each type of contact lens and 180 subjects totally for this study.

The recruitment will be divided into three stages. At the first stage, we will test 4 types of silicone hydrogel contact lenses, followed by testing 5 types of color-tinted hydrogel lenses at the second stage and 3 types of hydrogel lenses at the third stage. (T = types of lenses, which equals 4,5 and 3 at stage one, two and three).

At each stage, we will recruit subjects to certain amount (M) each time (M＝N×T , N equals 1,2,3…to 15). M subjects will then be randomized, equally distributed to wear T types of lenses by the random number method. Until the required case numberis achieved at the first stage, we will proceed to the second and the third stage with the same stratified randomization methods.( required case number, ΣM, equals 60, 75 and 45 at stage one, two and three).

Subjects are fitted with the soft contact lenses and are expected to wear the lenses for at least 6-8 hour per day. Standardized hand hygiene and lens care regimen are thoroughly explained to each subject to insert the contact lens. Each subject enrolled will be provided with the soft contact lenses without charge. After wear each day, the contact lenses must be returned and collected for material analysis.

Conditions

Keratitis; Infectious Disease (Manifestation)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Eligibility Criteria

Inclusion Criteria

1. age 20-35 years old

2. myopia less than -6.00D and astigmatism less than -1.50D

3. previous soft contact lens wear discontinued for at least 2 weeks. -

Exclusion Criteria

1. subjects with previous RGP wear

2. any ocular inflammation or infection, proved dry eye syndrome, glaucoma, ocular trauma or surgery, and topical medication instillation

3. diabetic mellitus

4. pregnancy

5. status post corneal refractive surgery -

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

HU FR Hu, professor

Role: STUDY_CHAIR

Locations

Department of Ophthlamology, National Taiwan University Hospital

Taipei, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Fung-rong Hu, Professor

Role: CONTACT

fungronghu@ntu.edu.tw

02-23123456 ext. 65189

Hsiao-sang Chu, Professor

Role: CONTACT

einahpets18@gmail.com

+886-928-980736

Facility Contacts

Fung-rong Hu, MD

Role: primary

fungronghu@ntu.edu.tw

+886-2-23123546 ext. 65819

Hsiao-sang Chu, MD

Role: backup

einahpets18@gmail.com

+886-928-980736

Other Identifiers

201212003RINC

Identifier Type: -

Identifier Source: org_study_id