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

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. At the Month 6, Month 12 and Month 18 visits, 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. Additionally,
beginning at the Month 4 visit, participants will be assessed for worsening disease defined
as loss of greater than or equal to 15 ETDRS letters of vision compared to baseline or a
greater than or equal to 50% increase in total retinal thickness as measured by OCT.
Participants deemed to have worsening disease beginning at their month 4 visit will also be
eligible to receive anti-VEGF treatments such as bevacizumab (Avastin(Registered Trademark))
or ranibizumab (Lucentis(Registered Trademark)) in their study eye. If participants do not
meet the criteria for improvement beginning at their month 6 visit, they will continue on
the study drug, but will be offered focal laser treatment and/or anti-VEGF treatment at the
discretion of the treating physician.

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 and 24 months compared to baseline, change in BCVA at 12 and 24
months compared to baseline, as well as changes in fluid leakage in the macula as
demonstrated by fluorescein angiography at 6, 12 and 24 months compared to baseline. Safety
outcomes include the number and severity of systemic and ocular toxicities, and adverse
events.