Diabetic Macular EdemaPhase 1/2NCT01120899

A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Diabetic Macular Edema

A Phase 1/2 study testing Minocycline in people with Diabetic Macular Edema, run by National Eye Institute (NEI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The objective of this study is to investigate the safety and efficacy of minocycline as a microglia inhibitor in individuals with diabetic macular edema (DME). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetic Macular Edema
What is being tested?: Minocycline
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 6 participants
Where: 1 siteUnited States
Study dates: Apr 2010to Feb 2013
Phase: Phase 1/2
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

Participant is 18 years of age or older.
Participant must understand and sign the protocol's informed consent document.
Female participants of childbearing potential (see Appendix 1 for definition) must not be pregnant or breast-feeding, must have a negative urine pregnancy test within 24 hours prior to initiation of study medication and must be willing to undergo urine pregnancy tests throughout the study.
Female participants of childbearing potential (see Appendix 1 for definition) and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for one week after study medication discontinuation (based on the half life of minocycline which is 11-22 hours). Acceptable methods of contraception include:
hormonal contraception (i.e., birth control pills*, injected hormones, dermal patch or vaginal ring),
intrauterine device,

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barrier methods (diaphragm, condom) with spermicide, or
surgical sterilization (hysterectomy or tubal ligation). *Oral birth control pills must be used with caution as minocycline decreases the effectiveness of some oral contraceptives. Participants already taking oral contraceptives may continue to use them, but must agree to use at least one other method of birth control while on study.
Participants must agree to notify the study investigator or coordinator if any of their doctors initiate a new medication during the course of this study.
Participant must have normal renal function and liver function or have mild abnormalities no greater than grade 1 as defined by the Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Refer to Appendix 2 for grading.
Participant has a diagnosis of diabetic mellitus (type 1 or type 2). Any one of the following will be considered to be sufficient evidence that diabetes is present:
Current regular use of insulin for the treatment of diabetes
Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes
Documented diabetes by American Diabetes Association (ADA) and/or World Health Organization (WHO) criteria
Participant has documented hemoglobin A1C 12% or less within one month of baseline.
Participant must agree to minimize exposure to sunlight or artificial UV rays and to wear protective clothing, sunglasses and sunscreen [minimum Sun Protection Factor (SPF) 15] if s/he must be out in the sun.
Participant has at least one eye that meets the study eye criteria listed below.

Who cannot join

Participant is in another investigational study and actively receiving study therapy.
Participant is unable to comply with study procedures or follow-up visits.
Participant has a known hypersensitivity to sodium fluorescein dye.
Participant has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control).
Patients in poor glycemic control who, within the last four months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next four months should not be enrolled.
Participant has a history of chronic renal failure requiring dialysis or kidney transplant.

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Participant has a history of hepatitis or liver failure.
Participant has an allergy or hypersensitivity to minocycline or any drug in the tetracycline family.
Participant is taking any medication that could adversely interact with minocycline such as methoxyflurane.
Participant has a blood pressure of > 180/110 (systolic above 180 OR diastolic above 110).
If blood pressure is brought below 180/110 by anti-hypertensive treatment, patient can become eligible.
Participant has a history of treatment with systemic anti-vascular endothelial growth factor (VEGF) agents or steroids within three months prior to study entry.
Participant has a history of thyroid cancer.
Study Eye Inclusion Criteria
Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity score between 78 and 39 letters (i.e., between 20/32 and 20/200).
Definite retinal thickening due to diabetic macular edema based on clinical exam involving the center of the macula that is not refractory to further therapy as based on the investigator's clinical judgment.
Previous treatment with focal laser photocoagulation following standard-of-care/best practice guidelines, as described by the ETDRS study,6 ≥ 3 months prior to enrollment unless the edema is not responsive to previous laser and/or not amenable to safe laser treatment at the discretion of the investigator. The laser treatment may be performed at the National Eye Institute (NEI) clinical center (CC) or by an outside ophthalmologist at the discretion of the participant and the investigator.
Retinal thickness in the central subfield on baseline optical coherence tomography (OCT) measurement > 250 microns, as measured by Spectral OCT.
Media clarity, pupillary dilation and patient cooperation sufficient for adequate fundus photographs.
Study Eye Exclusion Criteria
Macular edema is considered to be due to a cause other than diabetic macular edema.
An eye should not be considered eligible if:
The macular edema is considered to be related to cataract extraction or
Clinical exam and/or OCT suggest that vitreoretinal interface disease (e.g., a taut posterior hyaloid or epiretinal membrane) is the primary cause of the macular edema.
An ocular condition is present such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, non-retinal condition).
An ocular condition is present (other than diabetic retinopathy) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.).
Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by three lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).
History of panretinal scatter photocoagulation (PRP) within four months prior to study entry.
History of prior pars plana vitrectomy within six months prior to study entry.
History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within three months prior to study entry.
History of yttrium aluminium garnet (YAG) capsulotomy performed within two months prior to study entry.
History of treatment within three months prior to enrollment with any drug that has not received regulatory approval at the time of study entry, such as intravitreal or periocular steroids or intravitreal anti-VEGF agents.
Choice of Study Eye in Cases of Bilateral Disease
If both eyes of a participant meet the study eye inclusion and exclusion criteria listed above, the following will be used to determine the study eye:
If one eye is treatment-naïve and the other is not, the treatment-naïve eye will be chosen as the study eye.
If both eyes are treatment-naïve, the eye with the better visual acuity will be chosen as the study eye.
If both eyes are treatment-naïve and are equivalent, the choice of study eye will be determined at the investigator's discretion after consultation with the participant.
If both eyes have been previously treated, the choice of study eye will be determined at the investigator's discretion after consultation with the participant.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

The objective of this study is to investigate the safety and efficacy of minocycline as a microglia inhibitor in individuals with diabetic macular edema (DME).

Read the detailed description

Objective: Diabetic retinopathy (DR) is one of the leading causes of blindness in the United States. A frequent manifestation of diabetic retinopathy is diabetic macular edema (DME) for which the only proven treatment is laser photocoagulation. In the retina, microglia are capable of migrating through the retina to sites of inflammation to associate closely with neurons and the vasculature, and are key cellular players in the mediation of processes of chronic inflammation implicated in DME. For these reasons, microglia represent a promising cellular target for forms of therapy that limit the deleterious inflammatory changes found in DR. The objective of this study is to investigate the safety and efficacy of minocycline as a microglia inhibitor in patients with DME.

Study Population: Eligibility criteria include previous treatment with standard-of-care focal laser photocoagulation, or macular edema not amenable to focal laser treatment; retinal thickness in the central subfield > 250 microns as measured by optical coherence tomography (OCT); and visual acuity between 20/32 and 20/200 in the study eye.

Design: Five participants will be initially enrolled in this open-label pilot study. However, up to an additional three participants may be enrolled to account for participants who withdraw from the study prior to receipt of six months of study treatment. Participants will take an oral dose of 100 mg of minocycline twice daily for 24 months. During each visit, participants will have their visual acuity measured and will undergo OCT testing to measure retinal thickness. Beginning at the Month 6 visit, participants will be eligible for focal laser therapy unless they show marked improvement in retinal thickness and/or visual acuity or if they are not amenable to focal laser treatment. Participants who do not meet the criteria for improvement will also be eligible for anti-vascular endothelial growth factor (VEGF) treatments such as bevacizumab (Avastin®) or ranibizumab (Lucentis®). Additionally, beginning at the Month 4 visit, participants will be assessed for worsening disease defined as loss of ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters of vision compared to baseline or a ≥ 50% increase in total retinal thickness as measured by OCT. Participants deemed to have worsening disease will also be eligible for focal laser and/or anti-VEGF treatments.

Outcome Measures: The primary outcome is the change in best-corrected visual acuity (BCVA) in the study eye at 6 months compared to baseline. Secondary outcomes include the change in retinal thickness as measured by OCT at 6, 12, 18 and 24 months compared to baseline, change in BCVA at 12, 18 and 24 months compared to baseline, as well as changes in fluid leakage in the macula as demonstrated by fluorescein angiography at 6, 12, 18 and 24 months compared to baseline. Safety outcomes include the number and severity of systemic and ocular toxicities, and adverse events.

Conditions: Diabetic Macular Edema
Being tested: Minocycline
Keywords: Diabetic Macular Edema, Microglia, Minocycline, Diabetes
Medical subject headings: cyclopia sequence, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MinocyclineDrug
Also called Dynacin; serial number 73419626, Minocin; serial number 72309825, Minocin PAC, Myrac; serial number 76589055
Participants take 100 mg minocycline pills twice daily for 24 months.

Study groups in NCT01120899
Study group	Role	What they receive
Minocycline	Experimental	Not described Receives: Drug: Minocycline

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Study Eyes Demonstrating an Increase or Decrease in Best-corrected Visual Acuity (BCVA) of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters at 6 Months Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: 6 months

Secondary outcomes (16)

Change in BCVA in the Study Eye at 6 Months Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: Baseline and 6 Months
Change in BCVA in the Study Eye at 12 Months Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: Baseline and 12 Months
Change in BCVA in the Study Eye at 18 Months Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
Measured: Baseline and 18 Months
Change in BCVA in the Study Eye at 24 Months Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
Measured: Baseline and 24 Months
Percentage Change in Retinal Thickness in the Study Eye at 6 Months Compared to Baseline
Retinal thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: Baseline and 6 Months
Percentage Change in Retinal Thickness in the Study Eye at 12 Months Compared to Baseline
Retinal thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Measured: Baseline and 12 Months
Percentage Change in Retinal Thickness in the Study Eye at 18 Months Compared to Baseline
Retinal thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Measured: Baseline and 18 Months
Percentage Change in Retinal Thickness in the Study Eye at 24 Months Compared to Baseline
Retinal thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Measured: Baseline and 24 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 6 Months Compared to Baseline
Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: 6 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 12 Months Compared to Baseline
Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: 12 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 18 Months Compared to Baseline
Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: 18 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 24 Months Compared to Baseline
Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: 24 Months
Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 6 Months Compared to Baseline
Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: 6 Months
Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 12 Months Compared to Baseline
Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: 12 Months
Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 18 Months Compared to Baseline
Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: 18 Months
Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 24 Months Compared to Baseline
Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).
The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."
Measured: 24 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2010Feb 2013

First posted11 May 2010 (estimated)
Study startApr 2010
Primary completionAug 2011
Study completionFeb 2013

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 (4)Papers the sponsor has linked to this study.
Other trials for Diabetic Macular EdemaStudies 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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 6 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01120899
Sponsor's protocol ID: 100098
Other IDs: 10-EI-0098
Status last verified: Oct 2014
First submitted: 8 May 2010
Last updated: 17 Oct 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Kempen JH, O'Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, Taylor HR, Hamman RF; Eye Diseases Prevalence Research Group. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004 Apr;122(4):552-63. doi: 10.1001/archopht.122.4.552.
PubMed 15078674
Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology. 1984 Dec;91(12):1464-74. doi: 10.1016/s0161-6420(84)34102-1.
PubMed 6521986
Ferris FL 3rd, Patz A. Macular edema: a major complication of diabetic retinopathy. Trans New Orleans Acad Ophthalmol. 1983;31:307-16. No abstract available.
PubMed 6623578
Cukras CA, Petrou P, Chew EY, Meyerle CB, Wong WT. Oral minocycline for the treatment of diabetic macular edema (DME): results of a phase I/II clinical study. Invest Ophthalmol Vis Sci. 2012 Jun 22;53(7):3865-74. doi: 10.1167/iovs.11-9413.
PubMed 22589436

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Long-Term Follow-Up Study of RGX-314 Administered in the Suprachoroidal Space for Participants With and Without Diabetic Retinopathy
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RecruitingPhase 3
A Phase 3 Trial for Intravitreal Injection of 4D-150 in Adults With Diabetic Macular Edema (DME).
Diabetic Macular Edema (DME)
RecruitingPhase 2
Oral N-Acetylcysteine on Diabetic Macular Edema
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Active, not recruitingPhase 3
COMO: A Phase 3 Randomized, Double-Masked Study Comparing the Efficacy of EYP-1901 Against Aflibercept in DME
Diabetic Macular Edema, DME

All Diabetic Macular Edema trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Diabetic Macular Edema
ClinicalTrials.gov ID: NCT01120899
Acronym / sponsor ID: 100098
Conditions: Diabetic Macular Edema
Keywords: Diabetic Macular Edema, Microglia, Minocycline, Diabetes
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 6 participants (actual)
Lead sponsor: National Eye Institute (NEI)US National Institutes of Health
Collaborators: The Emmes Company, LLC
Study start: Apr 2010
Primary completion: Aug 2011 (actual)
Study completion: Feb 2013 (actual)
First posted: 11 May 2010 (estimated)
Results: Posted 6 Sep 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The objective of this study is to investigate the safety and efficacy of minocycline as a microglia inhibitor in individuals with diabetic macular edema (DME).

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Minocycline	Experimental	Drug: Minocycline

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (17 listed)

Participant is 18 years of age or older.
Participant must understand and sign the protocol's informed consent document.
Female participants of childbearing potential (see Appendix 1 for definition) must not be pregnant or breast-feeding, must have a negative urine pregnancy test within 24 hours prior to initiation of study medication and must be willing to undergo urine pregnancy tests throughout the study.
Female participants of childbearing potential (see Appendix 1 for definition) and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for one week after study medication discontinuation (based on the half life of minocycline which is 11-22 hours). Acceptable methods of contraception include:
Participants must agree to notify the study investigator or coordinator if any of their doctors initiate a new medication during the course of this study.

Key exclusion criteria (38 listed)

Participant is in another investigational study and actively receiving study therapy.
Participant is unable to comply with study procedures or follow-up visits.
Participant has a known hypersensitivity to sodium fluorescein dye.
Participant has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control).
Participant has a history of chronic renal failure requiring dialysis or kidney transplant.

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
MinocyclineAlso: Dynacin; serial number 73419626, Minocin; serial number 72309825, Minocin PAC, Myrac; serial number 76589055Participants take 100 mg minocycline pills twice daily for 24 months.	Drug	Minocycline

Primary outcome

Number of Study Eyes Demonstrating an Increase or Decrease in Best-corrected Visual Acuity (BCVA) of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters at 6 Months Compared to Baseline
Time frame: 6 months
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."

16 secondary outcomes

Change in BCVA in the Study Eye at 6 Months Compared to Baseline
Time frame: Baseline and 6 Months
Change in BCVA in the Study Eye at 12 Months Compared to Baseline
Time frame: Baseline and 12 Months
Change in BCVA in the Study Eye at 18 Months Compared to Baseline
Time frame: Baseline and 18 Months
Change in BCVA in the Study Eye at 24 Months Compared to Baseline
Time frame: Baseline and 24 Months
Percentage Change in Retinal Thickness in the Study Eye at 6 Months Compared to Baseline
Time frame: Baseline and 6 Months
Percentage Change in Retinal Thickness in the Study Eye at 12 Months Compared to Baseline
Time frame: Baseline and 12 Months
Percentage Change in Retinal Thickness in the Study Eye at 18 Months Compared to Baseline
Time frame: Baseline and 18 Months
Percentage Change in Retinal Thickness in the Study Eye at 24 Months Compared to Baseline
Time frame: Baseline and 24 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 6 Months Compared to Baseline
Time frame: 6 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 12 Months Compared to Baseline
Time frame: 12 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 18 Months Compared to Baseline
Time frame: 18 Months
Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 24 Months Compared to Baseline
Time frame: 24 Months
Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 6 Months Compared to Baseline
Time frame: 6 Months
Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 12 Months Compared to Baseline
Time frame: 12 Months
Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 18 Months Compared to Baseline
Time frame: 18 Months
Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 24 Months Compared to Baseline
Time frame: 24 Months

Results and safety

Results posted to the registry on 6 Sep 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Minocycline	6	3

Primary outcome: Number of Study Eyes Demonstrating an Increase or Decrease in Best-corrected Visual Acuity (BCVA) of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters at 6 Months Compared to Baseline

Time frame: 6 months. Number. Unit: Eyes

Measure	Minocycline n = 5
Value	1

16 secondary outcomes are reported in the full results.

Adverse events

Time frame: 18 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Minocycline	1 of 6 (16.7%)	6 of 6 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 15078674Kempen JH, O'Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, Taylor HR, Hamman RF; Eye Diseases Prevalence Research Group. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004 Apr;122(4):552-63. doi: 10.1001/archopht.122.4.552.
Background: PubMed 6521986Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology. 1984 Dec;91(12):1464-74. doi: 10.1016/s0161-6420(84)34102-1.
Background: PubMed 6623578Ferris FL 3rd, Patz A. Macular edema: a major complication of diabetic retinopathy. Trans New Orleans Acad Ophthalmol. 1983;31:307-16. No abstract available.
Results publication: PubMed 22589436Cukras CA, Petrou P, Chew EY, Meyerle CB, Wong WT. Oral minocycline for the treatment of diabetic macular edema (DME): results of a phase I/II clinical study. Invest Ophthalmol Vis Sci. 2012 Jun 22;53(7):3865-74. doi: 10.1167/iovs.11-9413.
NIH Clinical Center Detailed Web PageLink 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.

Catherine A Cukras, MD, PhD principal investigator

National Eye Institute (NEI)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Minocycline in people with Diabetic Macular Edema, run by National Eye Institute (NEI) 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 17 inclusion and 38 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 17 Oct 2014. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 6 Sep 2012). 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?

Number of Study Eyes Demonstrating an Increase or Decrease in Best-corrected Visual Acuity (BCVA) of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters at 6 Months Compared to Baseline (time frame: 6 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 NCT01120899, which also lists 4 linked publications.

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 17 Oct 2014.