Evaluation of Doxycyline for the Treatment of Nonproliferative and Early Proliferative Diabetic Retinopathy

Condition(s) targeted: Diabetic Retinopathy

Intervention: doxycycline monohydrate (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 University, Milton S. Hershey Medical Center
Ingrid U Scott, MD MPH, Principal Investigator, Affiliation: Penn State University, Milton S Hershey Medical Center

This 24 month randomized research study will evaluate whether doxycycline can 1) slow the deterioration or improve retinal function and/or 2) induce regression, or slow progression, of diabetic retinopathy in participants over 18 years of age with type 1 or type 2 diabetes with severe non-proliferative or early proliferative diabetic retinopathy.

Official title: Evaluation of Effect of Doxycyline Verses Placebo on Retinal Function and Posterior Segment Neovascularization in Patients With Severe Non-Proliferative or Early (Non-High-Risk) Proliferative Diabetic Retinopathy

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

Primary outcome: dark adaptation, scotopic visual fields, photopic visual fields, frequency doubling perimetry, ETDRS visual acuity, development or increase of neovascularization, need for panretinal photocoagulation, development of vitreous or preretinal hemorrhage

Secondary outcome: area of retinal thickening, central subfield thickness, macular volume, central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), arteriovenous ratio (AVR = CRAE/CRVE)

Detailed description: The objectives of this proof-of-concept study are to investigate whether doxycycline can 1) slow the deterioration or improve retinal function and/or 2) induce regression, or slow progression, of diabetic retinopathy. The tests will be performed in the Ophthalmology Departments of the Penn State College of Medicine and Glostrup Hospital, Copenhagen, Denmark. 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 severe non-proliferative diabetic retinopathy (ETDRS level 53E) or retinal and/or optic disk neovascularization >1/2 disc area and less than the "high-risk" characteristics defined by the Diabetic Retinopathy Study (17) (ETDRS level 65), and in whom panretinal photocoagulation is not imminently required in the ophthalmologist's judgment.

Systemic Exclusion Criteria:

- unstable medical status (e. g. glycemic control, blood pressure, cardiovascular disease)

in the opinion of investigator

- significant renal disease (defined as a serum creatinine > 2. 5 mg/dL),

- systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg

- pregnancy; for women of child-bearing potential, a urine pregnancy test will be

performed.

- lactating or intending to become pregnant during the study period (at least 24 months)

- sexually active women of child-bearing potential not actively practicing birth control

by using a medically accepted device or therapy (that is, intrauterine device, hormonal contraceptive, or barrier devices) during the study period (at least 24 months); since doxycycline may interfere with the effectiveness of hormonal contraceptives, sexually active women of child-bearing potential who use a hormonal contraceptive will be required to use a second form of contraception to safeguard against contraceptive failure while participating in the study

- known allergy/intolerance to doxycycline or any ingredient in the study drug or placebo

(e. g. hypromellose, iron oxide, methacrylic acid copolymer, polyethylene glycol, polysorbate 80, sugar spheres, talc, titanium dioxide, and triethyl citrate)

- patients taking phenytoin, barbiturates or carbamazepine, with gastroparesis, with a

history of gastrectomy, gastric bypass surgery or otherwise deemed achlorhydric or with a BMI > 30 kg/m2 will also be excluded because of altered doxycycline pharmacokinetics and/or bioavailability

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

- able and willing to give informed consent

- best-corrected ETDRS visual acuity in study eye ≥ 49 letters (20/100)

- severe non-proliferative diabetic retinopathy (ETDRS level 53E) (19) or retinal

and/or optic disk neovascularization >1/2 disc area and less than the "high-risk" characteristics defined by the Diabetic Retinopathy Study (ETDRS level 65) (17), and in whom panretinal photocoagulation is not imminently required in the ophthalmologist's judgment

- able to perform reliable visual field and dark adaptation testing

- central subfield thickness on OCT of ≤ 275microns

- foveal fixation present in each eye (assessed by fundus photography using an internal

fixation pointer or assessed by the investigator)

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

fluorescein angiograms

Exclusion Criteria:

- high-risk neovascularization in study eye

- prior panretinal photocoagulation in the study eye

- focal/grid laser photocoagulation in the macula within the past 15 weeks in the

study eye

- intraocular pressure > 22mmHg by Goldmann Tonometry

- history of pars plana vitrectomy in the study eye

- vitreous or pre-retinal hemorrhage 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 24 months

- best-corrected ETDRS visual acuity < 49 letters (20/100) in the fellow eye

- 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

- 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 College of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, United States

Penn State University, Milton S. Hershey Medical Center

Juvenile Diabetes Research Foundation

Penn State Hershey Eye Center, Department of Ophthalmology

Starting date: April 2008
Ending date: April 2012
Last updated: February 26, 2008