Diabetic RetinopathyPhase 2POC2NCT00917553
Evaluation of Effect of Doxycycline Verses Placebo on Retinal Function and 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 slow the deterioration or improve retinal function among patients with mild to moderate non-proliferative diabetic retinopathy. 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
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2009to Jul 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 (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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- Diabetic Retinopathy
- Being tested
- doxycycline monohydrate, Placebo
- Keywords
- diabetic retinopathy, diabetes, diabetic eye studies
- Medical subject headings
- Diabetic Retinopathy, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
doxycycline monohydrateDrug
50 mg
PlaceboDrug
Cellulose Placebo Capsule
| Study group | Role | What they receive |
|---|---|---|
| doxycycline monohydrate | Experimental | Not described Receives: Drug: doxycycline monohydrate |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Mean Change in the Foveal Sensitivity of Matrix Frequency Doubling Perimetry (FDP) From Baseline in the Treated Group Compared to the Placebo Group
Measured: Baseline and 24 months
Secondary outcomes (4)
Change Thickness Thickness
Anatomic outcomes were assessed through optical coherence. Positive numbers indicate increases in thickness.
Measured: Baseline and 24 months
Change in Macular Volume
Measured: Baseline and 24 months
Number of Participants With Progression to PDR, and Single or Multiple Step Progression in ETDRS Diabetic Retinopathy Severity Level
Participants are shown categorically by whether they reached PDR, or whether their diabetic retinopathy levels changed by one grade or more, as analyzed by fundus photography.
Measured: Baseline to 24 months
Number of Participants Who Developed Vitreous or Preretinal Hemorrhage
Any participants who developed vitreous or preretinal hemorrhage were counted. Had there been any preretinal hemorrhages (a subcategory of vitreous hemorrhage) these would have been shown as a separate row.
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 posted10 Jun 2009 (estimated)
- Study startJul 2009
- Primary completionJul 2012
- Study completionJul 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
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Gardner
- Sponsor type
- University, hospital or other
- Collaborators
- Penn State University, 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
- NCT00917553
- Sponsor's protocol ID
- 30791
- Acronym
- POC2
- Status last verified
- Oct 2018
- First submitted
- 1 Jun 2009
- Last updated
- 30 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Scott IU, Jackson GR, Quillen DA, Klein R, Liao J, Gardner TW. Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in mild to moderate nonproliferative diabetic retinopathy: a randomized proof-of-concept clinical trial. JAMA Ophthalmol. 2014 Sep;132(9):1137-42. doi: 10.1001/jamaophthalmol.2014.1422.
PubMed 24969516
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00917553
- Acronym / sponsor ID
- POC2 / 30791
- Conditions
- Diabetic Retinopathy
- Keywords
- diabetic retinopathy, diabetes, diabetic eye studies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Thomas GardnerUniversity, hospital or other
- Collaborators
- Penn State University, Juvenile Diabetes Research Foundation
- Study start
- Jul 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 10 Jun 2009 (estimated)
- Results
- Posted 30 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 slow the deterioration or improve retinal function among patients with mild to moderate non-proliferative diabetic retinopathy.
Detailed description
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.
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 monohydrate |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (13 listed)
- 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
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 monohydrate50 mg | Drug | doxycycline monohydrate |
| PlaceboCellulose Placebo Capsule | Drug | Placebo |
Primary outcome
The Mean Change in the Foveal Sensitivity of Matrix Frequency Doubling Perimetry (FDP) From Baseline in the Treated Group Compared to the Placebo Group
Time frame: Baseline and 24 months
4 secondary outcomes
Change Thickness Thickness
Time frame: Baseline and 24 months
Change in Macular Volume
Time frame: Baseline and 24 months
Number of Participants With Progression to PDR, and Single or Multiple Step Progression in ETDRS Diabetic Retinopathy Severity Level
Time frame: Baseline to 24 months
Number of Participants Who Developed Vitreous or Preretinal Hemorrhage
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 30 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24969516Scott IU, Jackson GR, Quillen DA, Klein R, Liao J, Gardner TW. Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in mild to moderate nonproliferative diabetic retinopathy: a randomized proof-of-concept clinical trial. JAMA Ophthalmol. 2014 Sep;132(9):1137-42. doi: 10.1001/jamaophthalmol.2014.1422.
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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 11 inclusion and 13 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 30 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 30 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?
The Mean Change in the Foveal Sensitivity of Matrix Frequency Doubling Perimetry (FDP) From Baseline in the Treated Group Compared to the Placebo Group (time frame: Baseline and 24 months). 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 NCT00917553, 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 30 Nov 2018.