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Evaluation of Doxycycline Verses Placebo for the Treatment of Severe Nonproliferative or Mild or Moderate Proliferative Diabetic Retinopathy (POC1)

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ClinicalTrials.gov Identifier: NCT00511875
Recruitment Status : Completed
First Posted : August 6, 2007
Results First Posted : November 2, 2018
Last Update Posted : November 2, 2018
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Thomas Gardner, Milton S. Hershey Medical Center

Tracking Information
First Submitted Date  ICMJE August 3, 2007
First Posted Date  ICMJE August 6, 2007
Results First Submitted Date September 8, 2018
Results First Posted Date November 2, 2018
Last Update Posted Date November 2, 2018
Study Start Date  ICMJE July 2008
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 30, 2018)
  • Change in Dark Adaptation, Rod Intercept [ Time Frame: Baseline and 24 months ]
    Change in dark adaptation is measured as dark adaptation time at baseline measured in minutes minus dark adaptation time measured at 24 months
  • Change in Photopic Visual Field [ Time Frame: Baseline and 24 months ]
    Change in photopic visual fields between baseline and 24 months
  • Change in Frequency Doubling Perimetry (FDP) [ Time Frame: 24 months ]
    Change in Frequency Doubling Perimetry (FDP) from baseline, shown as mean and foveal (center of retina) scores
  • Change in Early Treatment Diabetic Retinopathy Study (ETDRS) [ Time Frame: Baseline and 24 months ]
    Change in ETDRS visual acuity letter score from baseline. ETDRS is measured on a scale of 0 to 70 where 0 means inability to see anything on the chart and 70 is normal (20/20) acuity.
Original Primary Outcome Measures  ICMJE
 (submitted: August 3, 2007)
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 [ Time Frame: Over the study period ]
Change History Complete list of historical versions of study NCT00511875 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2018)
  • Change in Central Subfield Thickness [ Time Frame: Baseline and 24 months ]
    Change in central subfield thickness from baseline
  • Change in Macular Volume [ Time Frame: 24 months ]
    Change in macular volume from baseline
  • Change in Central Retinal Artery Equivalent (CRAE) Diameter [ Time Frame: 24 months ]
    Change in Central Retinal Artery Equivalent (CRAE) diameter from baseline
  • Change in Central Retinal Vein Equivalent (CRVE) Diameter [ Time Frame: 24 months ]
    Change in Central Retinal Vein Equivalent (CRVE) diameter from baseline
  • Change in Arteriovenous Ratio Diameter [ Time Frame: 24 months ]
    Change in arteriovenous ratio diameter from baseline
Original Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2007)
area of retinal thickening, central subfield thickness, macular volume, central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), arteriovenous ratio (AVR = CRAE/CRVE) [ Time Frame: Over the study period ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Doxycycline Verses Placebo for the Treatment of Severe Nonproliferative or Mild or Moderate Proliferative Diabetic Retinopathy
Official Title  ICMJE Evaluation of Effect of Doxycycline Verses Placebo on Diabetic Retinopathy Progression and Retinal Function in Patients With Severe Non-proliferative or Mild or Moderate (Non-high-risk) Proliferative Diabetic Retinopathy
Brief Summary 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.
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 mild or moderate proliferative diabetic retinopathy (retinal and /or optic disk neovascularization less than the "high-risk" ETDRS level 61 or 65), neovascularization of the disc or neovascularization elsewhere >1/2 disc area 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
  • history of headaches associated with tetracycline therapy
  • history of pseudotumor cerebri
  • pregnancy; for women of child-bearing potential, a serum 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. cellulose, 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
  • patients taking strontium, acitretin or tretinoin will be excluded due to the potential for serious drug interactions with doxycycline
  • patients with abnormal ALT or AST at baseline will be referred to their primary care physician for medical clearance for participation in this study
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Diabetic Retinopathy
Intervention  ICMJE
  • Drug: doxycycline monohydrate
    50mg once daily for 24 months
    Other Name: doxycycline
  • Drug: placebo
    placebo taken once daily for 24 months
Study Arms
  • Experimental: Doxycycline Monohydrate
    stratified equally to doxycycline monohydrate 50mg taken once daily for 24 months
    Intervention: Drug: doxycycline monohydrate
  • Placebo Comparator: Placebo
    stratified equally to placebo taken once daily for 24 months
    Intervention: Drug: placebo
Publications * Scott IU, Jackson GR, Quillen DA, Larsen M, Klein R, Liao J, Holfort S, Munch IC, Gardner TW. Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in patients with severe nonproliferative or non-high-risk proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol. 2014 May;132(5):535-43.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 30, 2018)
30
Original Estimated Enrollment  ICMJE
 (submitted: August 3, 2007)
60
Actual Study Completion Date May 2012
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • age ≥ 18 years old
  • diagnosis of type 1 or type 2 diabetes mellitus
  • have a hemoglobin A1c less than 11% at pre-qualification visit
  • 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) or retinal and/or optic disk neovascularization less than the "high-risk" characteristics defined by the Diabetic Retinopathy Study (ETDRS level61- 65), 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 in the study eye
  • 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
  • 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00511875
Other Study ID Numbers  ICMJE 25234
EudraCT number: 2007-005601-22
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Thomas Gardner, Milton S. Hershey Medical Center
Study Sponsor  ICMJE Thomas Gardner
Collaborators  ICMJE Juvenile Diabetes Research Foundation
Investigators  ICMJE
Study Director: Thomas W Gardner, MD MS University of Michigan, Kellogg Eye Center
PRS Account Milton S. Hershey Medical Center
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP