Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT00355459 |
| Other study ID # |
082005-026 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 2005 |
| Est. completion date |
April 2007 |
Study information
| Verified date |
December 2018 |
| Source |
University of Texas Southwestern Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this research project is to determine the effects of oral tetracycline such as
Minocycline (Minocin) on tear film composition and tear lipid (meibomian gland secretions)
characteristics in patients with chronic Blepharitis and associated dry eyes.
Description:
Tear film dysfunctions, which are collectively diagnosed as dry eye syndromes and Meibomian
Gland Dystrophy (MGD) afflict millions of individuals worldwide, more than 10 million in the
United States alone. Typically, symptoms include ocular burning, foreign body sensation,
photophobia, redness and other symptoms that result in overall chronic discomfort in
patients. Tetracycline analogues, such as minocycline, have demonstrated effectiveness in
treating primary meibomianitis, one type of chronic blepharitis and have been prescribed to
patients for sometime. It has been demonstrated that tetracycline can inhibit lipase activity
and therefore decrease the release of noxious free fatty acids. Tetracycline also inhibits
bacterial lipase activity in vitro and has other effects. We have been investigating the
associations between chronic blepharitis and eyelid meibomian gland lipids and microflora for
a number of years and have discovered important relationships between these lipids and
chronic blepharitis disease states. Because of its high concentration 12 hours post dose, low
renal clearance, long half life, and high level of binding to serum proteins, minocycline has
been suggested as a good treatment option. The study proposes to determine the effect of oral
treatment with tetracycline analogues on the Tear Film and Tear Lipid Composition within a
Population of Patients Diagnosed with Dry Eye Disease and Meibomian Gland Dysfunction.
Patients diagnosed with dry eye syndrome as well as Meibomian Gland Dystrophy (MGD) will be
selected to participate in a clinical study: baseline visit, 1-month following initiation of
treatment, 3-months after initiation of treatment, and 3-months after discontinuation of
treatment.
Once assessed and qualified to take part in the trial, participants will undergo the
following tests during each visit:
I. Ocular assessment of signs and symptoms II. Evaporometry III. Fluorophotometery IV.
Schirmers Testing V. TBUT VI. Bacteriology VII. Transillumination & Meibography VIII.
Meibomian gland expression and lipid analysis
After completion of the baseline visit, each patient will be given a 2-week regimen of 50-mg
dose of Minocycline followed by 10-week supply of 100-mg Minocycline to be taken daily after
breakfast. In addition, they can continue using artificial tears and additional treatments as
prescribed by their treating physicians.
I. Ocular assessment Patients' symptomology as well as the assessors' diagnostic findings
will be recorded and reviewed in detail before patient entrance into study. These include
visual acuity, biomicroscopy of lids/lashes, conjunctiva, and cornea. Moreover, corneal as
well as conjunctival staining will be performed with the use of two colored dyes: Lissamine
green and fluorescein. In addition, the investigator will record any pathology with the
patients' natural lens, iris, and pupil.
II. Evaporometer: Evaporative flow and contribution to turnover An evaporometer utilizes a
pump to direct air through a drying tube (Hammond Drierite, Xenia, OH) into a goggle. The
goggle containing a water vapor detector and a temperature monitor is placed firmly over the
eye. The pumped air passes into the goggle, reducing the humidity to 15%, at which time the
pump is turned off. The increase in humidity due to evaporation from skin or evaporating
tears is measured and stored in a computer. The process is carried out first with the eyelids
closed and then with them open; the difference is the tear evaporation rate. The area of the
interpalpebral ocular surface is used to calculate evaporation per unit area; the image of
the area is captured with the use of a digital camera and calculated directly with the aid of
computer software (ADOBE Photoshop, version 6.0.1.2001, ADOBE Systems, and San Jose,
California). Evaporative outflow as a percentage of available tear volume will be calculated
from the rate of the rise of relative humidity inside the goggle with the eye open minus the
evaporative contribution of the closed eye skin within the goggle.
The evaporative contribution to turnover will be calculated as evaporative outflow per
available tear volume per minute divided by tear turnover.
III. Fluorophotometer: Tear volume, flow and turnover Background fluorescence will be
determined prior to the instillation of 0.5 micro liters of 0.5% sodium fluorescein onto the
ocular surface. Utilizing a fluorophotometer (Fluorotron Master, Ocumetrics, Mountain View,
CA), eight measurements will be taken from each eye to determine tear fluorescence. The first
two measurements will be performed one minute apart and subsequent measurements will be
repeated with three minute intervals until completion at 19 minutes. This data will be
analyzed to calculate tear volume, flow and tear turnover.
IV. Schirmers testing: Quantitative tear measurement performed with and without anesthetic
Drops. A commonly used paper wick will be placed between the eyeball and outer third of the
lower lid cul-de-sac in order to measure quantitatively the production of tears. This test
typically takes 5 minutes to perform.
V. Tear Break-Up Time - Quantitative/Qualitative assessment of corneal and conjunctival dry
spots (devitalized surface epithelial cells) A drop of fluorescein will be instilled in both
eyes of the patient. Patient will be asked to blink normally for the dye to spread evenly in
the eye. Once completed, patient will be asked to blink once and hold eyes open while the
assessor uses a stop watch to record number of seconds it takes for the tear film to
break-up. This is a tool that allows the examiner to grade the quality of the tear film.
Normal control patient TBUT is 10-12 seconds while a dry eye patient TBUT is less than 2
seconds.
VI. Bacteriology - Eyelid microflora evaluation Samples of eyelid and conjunctival microflora
of each eye will be taken separately with a calcium alginate swab dipped in 0.9% salt
solution. After streaking the swab on different plates (blood agar, chocolate agar, and
reduced brucella blood agar), it will placed into a tube of thioglycolate for bacteriological
assessment.
VII. Transillumination & Meibography - Quantitative assessment of lower lid meibomian gland
lipid production An excretory gland, the primary role of the meibomian glands is to produce
and secrete lipids into the tear film. The purpose of this test is to determine
quantitatively the number of lower lid glands that are functional lipid producers. A
transilluminator (muscle light) with a light dispersing tip will be used to illuminate the
glands. The small band of light will transilluminate the inverted lower lids of patients.
With the use of a digital camera, a picture will be taken in order to assess vital glands
from drop-outs (non-producing glands). This is accomplished with a frame grabber that is
matched to a Hitachi KP-F2A progressive scanner infrared camera that is mounted on a slit
lamp microscope. Images will be captured and stored with the use of imaging software.
VIII. Meibomian gland expression and lipid analysis - Lower and Upper eye lid samples will be
collected and assayed for their biochemical makeup With the use of an ocular conformer and
cotton tip applicator, samples of upper and lower lid meibomian gland lipids will be
collected and assessed for make-up
