Diabetic RetinopathyPhase 2POC1NCT00511875
Evaluation of Doxycycline Verses Placebo for the Treatment of Severe Nonproliferative or Mild or Moderate Proliferative Diabetic Retinopathy
A Phase 2 study testing doxycycline monohydrate in people with Diabetic Retinopathy, run by Thomas Gardner at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Retinopathy
- What is being tested?
- doxycycline monohydrate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to May 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: 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
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.
Read the 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
- Conditions
- Diabetic Retinopathy
- Being tested
- doxycycline monohydrate, placebo
- Keywords
- diabetic retinopathy, diabetes, diabetic eye studies, neovascularization
- Medical subject headings
- Diabetic Retinopathy, Diabetes Mellitus, Neovascularization, Pathologic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
doxycycline monohydrateDrug
Also called doxycycline
50mg once daily for 24 months
placeboDrug
placebo taken once daily for 24 months
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline Monohydrate | Experimental | stratified equally to doxycycline monohydrate 50mg taken once daily for 24 months Receives: Drug: doxycycline monohydrate |
| Placebo | Placebo comparator | stratified equally to placebo taken once daily for 24 months Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline and 24 months
Change in Photopic Visual Field
Change in photopic visual fields between baseline and 24 months
Measured: 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
Measured: 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.
Measured: Baseline and 24 months
Secondary outcomes (5)
Change in Central Subfield Thickness
Change in central subfield thickness from baseline
Measured: Baseline and 24 months
Change in Macular Volume
Change in macular volume from baseline
Measured: 24 months
Change in Central Retinal Artery Equivalent (CRAE) Diameter
Change in Central Retinal Artery Equivalent (CRAE) diameter from baseline
Measured: 24 months
Change in Central Retinal Vein Equivalent (CRVE) Diameter
Change in Central Retinal Vein Equivalent (CRVE) diameter from baseline
Measured: 24 months
Change in Arteriovenous Ratio Diameter
Change in arteriovenous ratio diameter from baseline
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2007 (estimated)
- Study startJul 2008
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic RetinopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Gardner
- Sponsor type
- University, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation
- Responsible party
- Sponsor-investigator, Thomas Gardner, Milton S. Hershey Medical Center
- Investigators
- Thomas W Gardner, MD MS, Study director, University of Michigan, Kellogg Eye Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00511875
- Sponsor's protocol ID
- 25234
- Other IDs
- EudraCT number: 2007-005601-22
- Acronym
- POC1
- Status last verified
- Oct 2018
- First submitted
- 3 Aug 2007
- Last updated
- 2 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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. doi: 10.1001/jamaophthalmol.2014.93.
PubMed 24604308
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00511875
- Acronym / sponsor ID
- POC1 / 25234
- Conditions
- Diabetic Retinopathy
- Keywords
- diabetic retinopathy, diabetes, diabetic eye studies, neovascularization
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Thomas GardnerUniversity, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation
- Study start
- Jul 2008
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 6 Aug 2007 (estimated)
- Results
- Posted 2 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Doxycycline Monohydrate | Experimental | Drug: doxycycline monohydratestratified equally to doxycycline monohydrate 50mg taken once daily for 24 months |
| Placebo | Placebo comparator | Drug: placebostratified equally to placebo taken once daily for 24 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| doxycycline monohydrateAlso: doxycycline50mg once daily for 24 months | Drug | Doxycycline Monohydrate |
| placeboplacebo taken once daily for 24 months | Drug | Placebo |
Primary outcome
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.
5 secondary outcomes
Change in Central Subfield Thickness
Time frame: Baseline and 24 months
Change in Macular Volume
Time frame: 24 months
Change in Central Retinal Artery Equivalent (CRAE) Diameter
Time frame: 24 months
Change in Central Retinal Vein Equivalent (CRVE) Diameter
Time frame: 24 months
Change in Arteriovenous Ratio Diameter
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24604308Scott 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.
- Penn State University, Milton S. Hershey Medical CenterLink provided by the sponsor.
- Juvenile Diabetes Research FoundationLink provided by the sponsor.
- Penn State Hershey Eye Center, Department of OphthalmologyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas W Gardner, MD MS study director
University of Michigan, Kellogg Eye Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing doxycycline monohydrate in people with Diabetic Retinopathy, run by Thomas Gardner at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Dark Adaptation, Rod Intercept (time frame: Baseline and 24 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00511875, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2018.