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

This study has been completed.
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Thomas W. Gardner, Penn State University
ClinicalTrials.gov Identifier:
NCT00511875
First received: August 3, 2007
Last updated: October 4, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Diabetic Retinopathy
Drug: doxycycline monohydrate
Drug: placebo
Phase 2

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: Evaluation of Effect of Doxycyline 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

Resource links provided by NLM:


Further study details as provided by Penn State University:

Primary Outcome Measures:
  • dark adaptation, 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: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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: 2 years ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: July 2008
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
stratified equally to doxycycline monohydrate 50mg taken once daily for 24 months
Drug: doxycycline monohydrate
50mg once daily for 24 months
Other Name: doxycycline
Placebo Comparator: Placebo
stratified equally to placebo taken once daily for 24 months
Drug: placebo
placebo taken once daily for 24 months

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
  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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00511875

Locations
United States, Pennsylvania
Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Thomas W. Gardner
Juvenile Diabetes Research Foundation
Investigators
Study Director: Thomas W Gardner, MD MS University of Michigan, Kellogg Eye Center
  More Information

Additional Information:
No publications provided by Penn State University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Thomas W. Gardner, Thomas W. Gardner, MD, Penn State University
ClinicalTrials.gov Identifier: NCT00511875     History of Changes
Other Study ID Numbers: 25234, EudraCT number: 2007-005601-22
Study First Received: August 3, 2007
Last Updated: October 4, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Penn State University:
diabetic retinopathy
diabetes
diabetic eye studies
neovascularization

Additional relevant MeSH terms:
Diabetic Retinopathy
Retinal Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Doxycycline
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on August 20, 2014