Exudative Macular Degeneration, Wet Age-related Macular Degeneration
Conditions
Keywords
Active choroidal neovascularization (CNV)
Brief summary
Wet (or neovascular) form of age-related macular degeneration (wAMD) is the most common cause of blindness in the Western world. Currently, anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVI) remain the standard-of-care treatment for wAMD. Previous studies show that about 90% of treated patients lose minimal visual function after 2 years of follow-up. There is still, a subset of 15% patients, incomplete responders, that do not improve and possibly worsen due to the persistence of sub-retinal fluid (with or without intra-retinal fluid) with chronic treatment. The investigators plan to evaluate the effect of oral doxycycline versus placebo on the anatomic and functional outcomes in persistent sub-retinal eye fluid in neovascular wet age-related macular degeneration. This subset are incomplete or non-responders to current anti-VEGF intravitreal therapy.
Detailed description
The investigators plan to conduct a double masked, randomized study to assess the effect of low dose, oral doxycycline 50 mg once a day versus placebo in patients with wet age-related macular degeneration who are incomplete responders to anti-VEGF extended treatment regimens. The study will be conducted over 9 months with every 3 month assessments; 6 months administration period of doxycycline versus placebo (double masked, randomized) and a 3 month follow up period. The participant visits will occur during clinic visits for standard-of-care intravitreal injections (IVI). Medical information will be acquired from the standard of care optical coherence tomography (OCT), visual acuity (VA), and IVI administered (number, frequency and type of drug). Blood plasma and aqueous fluid (anterior chamber tap) samples and study drug tolerability will be obtained at baseline, 6 months and 9 months. Plasma will be obtained to assay for inflammatory markers: MMP-9 levels and questionnaires will be obtained on 1) vision quality of life, and 2) study drug tolerance at Baseline, 6 months and 9 months.
Interventions
Doxycycline Hyclate capsules, USP 50 mg
DRUGPlacebo
Placebo
Sponsors
University of Iowa
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Over encapsulation with opaque purple capsule
Intervention model description
Doxycycline Hyclate 50 mg versus placebo capsule
Eligibility
Sex/Gender
ALL
Age
50 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Wet age-related macular degeneration (wAMD); * Solely treated with anti-VEGF IVI for active CNV due to wAMD. However, enrolled patients can have other retinal pathologies such as diabetic retinopathy or vein occlusion for which they are not being treated with anti-VEGF IVI; * Must have persistent sub-retinal with or without intra-retinal fluid due to active CNV from wAMD despite receiving at least three consecutive injections with any anti-VEGF agent; * Must not have encountered previous side effects from tetracycline medications.
Exclusion criteria
- Ocular: * History of uveitis (including endophthalmitis) or presence of intraocular inflammation; * Presence of significant epiretinal membrane or macular hole causing distortion of macular anatomy; * Presence of media opacity preventing discerning of fluid on OCT; * Any prior ophthalmic surgery (including YAG or retinal laser) within the previous 3 months or anticipated need for any ophthalmic surgery (including cataract extraction) for 9 months following randomization; * History of peribulbar corticosteroid injection to the studied eye or the fellow eye within the past 6 months; * History of intravitreal triamcinolone acetonide injection to the studied eye within the past 4 months; * An ocular condition (other than AMD) is present in the studied 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, and Irvine-Gass syndrome); * CNV due to causes other than wAMD; * Inability to follow up at the 6th and 9th months time points after recruitment; * Missing two or more consecutive injections during the six months treatment period; * Patient requiring imminent need for IVI anti-VEGF medication switch or another treatment intervention, such as photodynamic therapy, during the 9 months trial period; * Presence of fluid associated with geographic atrophy or disciform scar; * Any patient with sub-retinal and/or intra-retinal fluid that is not due to CNV (eg, overlying areas of geographic atrophy; * Any patient actively being actively treated for Irvine-Gass Syndrome.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resolution of the persistent retinal fluid on optical coherence tomography (OCT) | 9 months | percentage of patients with retinal fluid-free status |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in optical coherence tomography (OCT) central media thickness (CMT) | 9 months compared to baseline | mean change in central media thickness |
| Change in best corrected visual acuity (BCVA) | 6 months and 9 months compared to Baseline | mean change in logMAR / percentage of patients with a gain or loss of more than 5 ETDRS letters |
| Number of intravitreal injections (IVI) administered | 6 months and 9 months | total number of anti-VEGF intravitreal injections |
| Inflammatory mediators matrix metalloproteinases MMP-9 and MMP-9 activity | Baseline, 6 months and 9 months | anterior eye aqueous fluid and blood plasma |
Countries
United States
Contacts
CONTACTElliott H Sohn, MD
PRINCIPAL_INVESTIGATORElliott H Sohn, MD
University of Iowa
Outcome results
None listed