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

NCT00511875 | Completed Phase 2 Results DMC

• 2 other identifiers: 25234EudraCT number: 2007-005601-22
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetic Retinopathy

Keywords

diabetic retinopathy; diabetes; diabetic eye studies; neovascularization

Outcome Measures

Primary Outcomes (4)

• Change in Dark Adaptation, Rod Intercept

  Change in dark adaptation is measured as dark adaptation time at baseline measured in minutes minus dark adaptation time measured at 24 months

  Baseline and 24 months

• Change in Photopic Visual Field

  Change in photopic visual fields between baseline and 24 months

  Baseline and 24 months

• Change in Frequency Doubling Perimetry (FDP)

  Change in Frequency Doubling Perimetry (FDP) from baseline, shown as mean and foveal (center of retina) scores

  24 months

• Change in Early Treatment Diabetic Retinopathy Study (ETDRS)

  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.

  Baseline and 24 months

Secondary Outcomes (5)

• Change in Central Subfield Thickness

  Baseline and 24 months

• Change in Macular Volume

  24 months

• Change in Central Retinal Artery Equivalent (CRAE) Diameter

  24 months

• Change in Central Retinal Vein Equivalent (CRVE) Diameter

  24 months

• Change in Arteriovenous Ratio Diameter

  24 months

Study Arms (2)

Doxycycline Monohydrate

EXPERIMENTAL

stratified equally to doxycycline monohydrate 50mg taken once daily for 24 months

Drug: doxycycline monohydrate

Placebo

PLACEBO COMPARATOR

stratified equally to placebo taken once daily for 24 months

Drug: placebo

Interventions

doxycycline monohydrate DRUG

50mg once daily for 24 months

Also known as: doxycycline

Doxycycline Monohydrate

placebo DRUG

placebo taken once daily for 24 months

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Thomas Gardner: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

Penn State College of Medicine, Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (1)

• 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. doi: 10.1001/jamaophthalmol.2014.93.

  PMID: 24604308 DERIVED

Related Links

• Penn State University, Milton S. Hershey Medical Center
• Juvenile Diabetes Research Foundation
• Penn State Hershey Eye Center, Department of Ophthalmology

MeSH Terms

Conditions

Diabetic Retinopathy; Diabetes Mellitus; Neovascularization, Pathologic

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

This is a proof of concept study.

Results Point of Contact

• Title: Dr. Thomas W. Gardner
• Organization: University of Michigan

tomwgard@med.umich.edu

734 232-8404

Study Officials

• Thomas W Gardner, MD MS

  University of Michigan, Kellogg Eye Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Thomas W. Gardner, MD

Study Record Dates

• First Submitted: August 3, 2007
• First Posted: August 6, 2007
• Study Start: July 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: November 2, 2018
• Results First Posted: November 2, 2018

Record last verified: 2018-10

Locations

US (1)