search
Back to results

Evaluation of Effect of Doxycycline Verses Placebo on Retinal Function and Diabetic Retinopathy (POC2)

Primary Purpose

Diabetic Retinopathy

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
doxycycline monohydrate
Placebo
Sponsored by
Thomas Gardner
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Retinopathy focused on measuring diabetic retinopathy, diabetes, diabetic eye studies

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Penn State Milton S. Hershey Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

doxycycline monohydrate

Placebo

Arm Description

Placebo

Outcomes

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

Secondary Outcome Measures

Change Thickness Thickness
Anatomic outcomes were assessed through optical coherence. Positive numbers indicate increases in thickness.
Change in Macular Volume
Number of Participants With Progression to PDR, and Single or Multiple Step Progression in ETDRS Diabetic Retinopathy Severity Level
Participants are shown categorically by whether they reached PDR, or whether their diabetic retinopathy levels changed by one grade or more, as analyzed by fundus photography.
Number of Participants Who Developed Vitreous or Preretinal Hemorrhage
Any participants who developed vitreous or preretinal hemorrhage were counted. Had there been any preretinal hemorrhages (a subcategory of vitreous hemorrhage) these would have been shown as a separate row.

Full Information

First Posted
June 1, 2009
Last Updated
October 30, 2018
Sponsor
Thomas Gardner
Collaborators
Penn State University, Juvenile Diabetes Research Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT00917553
Brief Title
Evaluation of Effect of Doxycycline Verses Placebo on Retinal Function and Diabetic Retinopathy
Acronym
POC2
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 Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Thomas Gardner
Collaborators
Penn State University, Juvenile Diabetes Research Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Retinopathy
Keywords
diabetic retinopathy, diabetes, diabetic eye studies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
doxycycline monohydrate
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
doxycycline monohydrate
Intervention Description
50 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Cellulose Placebo Capsule
Primary Outcome Measure Information:
Title
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
Baseline and 24 months
Secondary Outcome Measure Information:
Title
Change Thickness Thickness
Description
Anatomic outcomes were assessed through optical coherence. Positive numbers indicate increases in thickness.
Time Frame
Baseline and 24 months
Title
Change in Macular Volume
Time Frame
Baseline and 24 months
Title
Number of Participants With Progression to PDR, and Single or Multiple Step Progression in ETDRS Diabetic Retinopathy Severity Level
Description
Participants are shown categorically by whether they reached PDR, or whether their diabetic retinopathy levels changed by one grade or more, as analyzed by fundus photography.
Time Frame
Baseline to 24 months
Title
Number of Participants Who Developed Vitreous or Preretinal Hemorrhage
Description
Any participants who developed vitreous or preretinal hemorrhage were counted. Had there been any preretinal hemorrhages (a subcategory of vitreous hemorrhage) these would have been shown as a separate row.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas W Gardner, MD.,MS.
Organizational Affiliation
University of Michigan, Kellogg Eye Center
Official's Role
Study Director
Facility Information:
Facility Name
Penn State Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24969516
Citation
Scott IU, Jackson GR, Quillen DA, Klein R, Liao J, Gardner TW. Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in mild to moderate nonproliferative diabetic retinopathy: a randomized proof-of-concept clinical trial. JAMA Ophthalmol. 2014 Sep;132(9):1137-42. doi: 10.1001/jamaophthalmol.2014.1422.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs