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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- The Mean Change in the Foveal Sensitivity of Matrix Frequency Doubling Perimetry (FDP) From Baseline in the Treated Group Compared to the Placebo Group
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
doxycycline monohydrate
干预措施: doxycycline monohydrate (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
The Mean Change in the Foveal Sensitivity of Matrix Frequency Doubling Perimetry (FDP) From Baseline in the Treated Group Compared to the Placebo Group
时间窗: Baseline and 24 months
次要结局
- Change Thickness Thickness(Baseline and 24 months)
- Change in Macular Volume(Baseline and 24 months)
- Number of Participants With Progression to PDR, and Single or Multiple Step Progression in ETDRS Diabetic Retinopathy Severity Level(Baseline to 24 months)
- Number of Participants Who Developed Vitreous or Preretinal Hemorrhage(24 months)
研究者
Thomas Gardner
Thomas W. Gardner, MD
Milton S. Hershey Medical Center