Evaluation of Effect of Doxycycline Verses Placebo on Retinal Function and Diabetic Retinopathy - Full Text View

Sponsor:	Penn State University
Collaborator:	Juvenile Diabetes Research Foundation
Information provided by:	Penn State University
ClinicalTrials.gov Identifier:	NCT00917553

Purpose

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.

Condition	Intervention	Phase
Diabetic Retinopathy	Drug: doxycycline monohydrate Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetic Eye Problems Retinal Disorders

Drug Information available for: Doxycycline Doxycycline hyclate Doxycycline calcium

U.S. FDA Resources

Further study details as provided by Penn State University:

Primary Outcome Measures:

The mean change in the foveal sensitivity of Matrix frequency doubling perimetry (FDP) from baseline in the treated group compared to the placebo group [ Time Frame: From baseline to 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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. [ Time Frame: The secondary outcome measures will be assessed from baseline to 24 months. ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	July 2009
Estimated Study Completion Date:	July 2012
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: doxycycline monohydrate	Drug: doxycycline monohydrate 50 mg
Placebo Comparator: Placebo Placebo	Drug: Placebo Cellulose Placebo Capsule

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 the investigators evaluated in the END DR Study. This selection is aggressive because the investigators 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. The investigators 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

age ≥ 18 years old
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00917553

Locations

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

Sponsors and Collaborators

Penn State University

Juvenile Diabetes Research Foundation

Investigators

Study Director:

Thomas W Gardner, MD.,MS.

University of Michigan, Kellogg Eye Center

More Information

No publications provided

Responsible Party:	Thomas W. Gardner, MD.,MS., Penn State College of Medicine
ClinicalTrials.gov Identifier:	NCT00917553 History of Changes
Other Study ID Numbers:	30791
Study First Received:	June 1, 2009
Last Updated:	August 1, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Penn State University:

diabetic retinopathy
diabetes
diabetic eye studies

Additional relevant MeSH terms:

Diabetic Retinopathy
Retinal Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases

Doxycycline
Doxycycline hyclate
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on February 09, 2012