Evaluation of Effect of Doxycycline Verses Placebo on Retinal Function and Diabetic Retinopathy

Condition(s) targeted: Diabetic Retinopathy

Intervention: doxycycline monohydrate (Drug); Placebo (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Penn State University

Official(s) and/or principal investigator(s):
Thomas W Gardner, MD.,MS., Study Director, Affiliation: Penn State College of Medicine

This 24 month randomized research study will evaluate whether doxycycline can slow the deterioration or improve retinal function among patients with mild to moderate non-proliferative diabetic retinopathy.

Official title: Proof-of-Concept 2 (POC2): Evaluation of Effect of Doxycycline Verses Placebo on Retinal Function and Diabetic Retinopathy Progression in Patients With Mild to Moderate Non-Proliferative Diabetic Retinopathy

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: The mean change in the foveal sensitivity of Matrix frequency doubling perimetry (FDP) from baseline in the treated group compared to the placebo group

Secondary outcome: The functional and anatomic outcomes will be assessed by comparing the placebo group with the treated group in this proof-of-concept study in the following procedures; visual functions tests, fundus photography and optical coherence.

Detailed description: The objective of this proof-of-concept study is to investigate whether doxycycline can slow the deterioration or improve retinal function among patients with mild to moderate NPDR (with abnormal retinal function defined as a foveal sensitivity < 30. 91 dB on Matrix frequency doubling perimetry [FDP]). Based on results of the END DR Study, the primary visual function endpoint in the POC 2 Study will be performance on the Matrix Frequency Doubling Technology Perimeter. This test was the most sensitive to NPDR of the visual function endpoints we evaluated in the END DR Study. This selection is aggressive because we lack natural history data to estimate the 2-year rate of change in the endpoint; in fact, a major output of this POC 2 Study will be 2-year natural history data using several visual function endpoints. We are enrolling patients who have moderate dysfunction; that is, patients who fall outside the 95% confidence interval of normal performance on FDP. These patients will have the opportunity to improve their FDP performance to "normal" levels as well as progress to more severe FDP impairment associated with more advanced disease. Secondary endpoints include visual acuity, contrast sensitivity, visual field, and dark adaptation. The tests will be performed in the Ophthalmology Department of the Penn State College of Medicine. The 24-month proof-of-concept clinical study will involve a prospective, randomized, double-masked clinical trial including 60 adult patients with type 1 or type 2 diabetes who have mild to moderate NPDR (ETDRS levels 20 to 43), and in whom retinal photocoagulation is not anticipated (by the investigator) within the subsequent 2 years. Participants will be randomized to receive either doxycycline monohydrate 50mg or an identical placebo once daily for 24 months.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- age ≥ 18 years

- diagnosis of type 1 or type 2 diabetes mellitus (defined as current regular use of

oral anti-hyperglycemia agents and/or insulin for the treatment of diabetes)

- have a hemoglobin A1c < 11% at pre-qualification visit

- able and willing to give informed consent

- best-corrected ETDRS visual acuity (10) in study eye ≥ 69 letters (20/40)

- mild to moderate non-proliferative diabetic retinopathy (ETDRS levels 20 to 43) (11),

and in whom retinal photocoagulation is not anticipated (by the investigator) within the subsequent 2 years

- able to perform reliable visual field and dark adaptation testing

- central subfield thickness on OCT ≤ 275 microns

- media clarity and pupil dilation sufficient for high-quality fundus photographs

- abnormal retinal function defined as:

- abnormal FDP function as defined by a foveal sensitivity ≤ 30. 91 dB

Exclusion Criteria:

- prior panretinal photocoagulation in the study eye

- prior focal/grid laser photocoagulation in the macula in the study eye

- intraocular pressure in the study eye > 22 mmHg by Goldmann tonometry

- history of pars plana vitrectomy in the study eye

- systemic or intravitreal anti-VEGF agent to the study eye or the fellow eye within

the past 3 months

- peribulbar steroid injection to the study eye or the fellow eye within the past 6

months

- intravitreal triamcinolone acetonide to the study eye within the past 4 months

- expectation by the investigator that retinal photocoagulation or other treatment for

diabetic retinopathy (e. g., focal/grid laser to study eye, intravitreal triamcinolone acetonide to study eye, intravitreal anti-VEGF agent to study or fellow eye, ruboxistaurin or systemic anti-VEGF agent for diabetic macular edema) will be administered in the subsequent 24months

- an ocular condition (other than diabetes) is present in the study eye that, in the

opinion of the investigator, might alter visual acuity during the course of the study (e. g., retinal vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc)

- anticipated need for cataract surgery in the study eye in the subsequent 24 months in

the opinion of the investigator

- history of major ocular surgery (including cataract surgery, scleral buckle, any

intraocular surgery, etc) in the study eye within prior 6 months or anticipated within the subsequent 24 months following randomization

- aphakia in the study eye

- history of YAG capsulotomy performed in the study eye within 2 months prior to

randomization

Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, United States

Starting date: June 2009
Ending date: June 2011
Last updated: June 9, 2009