Recruiting
Phase 2

MMP-9 Inhibition

Sponsor:

University of Iowa

Code:

NCT04504123

Conditions

Exudative Macular Degeneration

Wet Age-related Macular Degeneration

Eligibility Criteria

Sex: All

Age: 50 - 70+

Healthy Volunteers: Not accepted

Interventions

Doxycycline Hyclate

Placebo

Study Details

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.

Conditions

Exudative Macular Degeneration

Wet Age-related Macular Degeneration

Study ID

NCT04504123

Start date

Nov 4, 2020

Status verified date

Mar, 2026

Completion date

Mar 1, 2027

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 50 - 70+

Healthy Volunteers: Not accepted

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.

Exclusion Criteria - Systemic:

  • Patient with and/or who developed an unstable medical status (e.g., glycemic control, blood pressure, cardiovascular disease, individuals who are unlikely or unable to complete the 9 months trial period) in the opinion of the 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;
  • History of tetracycline therapy within the past 6 months;
  • Pregnancy or patient intending to become pregnant within the 9 months of the trial period. For women of child-bearing potential, a pregnancy test will be performed;
  • Sexually active women of child-bearing potential not actively practicing birth control by using a medically accepted device or therapy (i.e., intrauterine device, hormonal contraceptive, or barrier device) during the study period (at least 24 months). This is important as doxycycline may interfere with the effectiveness of hormonal contraceptives. Hence, 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, tetracyclines, or any ingredient in the study drug or placebo;
  • Patients receiving phenytoin, barbiturates, carbamazepine, digoxin, or isotretinoin; patients with gastroparesis; patients with a history of gastrectomy, gastric bypass surgery, or otherwise deemed achlorhydric should all be excluded due to altered doxycycline pharmacokinetics and/or bioavailability;
  • Patients taking strontium, acitretin, or tretinoin should excluded due to the potential for serious 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

Enrollment

50 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Doxycycline

Participants received doxycycline hyclate 50 mg capsule orally once a day for 6 months

placebo comparator: Placebo

Participants received placebo (inactive) capsule orally once a day for 6 months

Interventions

Doxycycline Hyclate

Doxycycline Hyclate capsules, USP 50 mg

Placebo

Placebo

Primary outcome measure

  • Resolution of the persistent retinal fluid on optical coherence tomography (OCT) [ Time Frame: 9 months ]

Central Contacts and Locations

Central contacts

Elliott H Sohn, MD

3193563285elliott-sohn@uiowa.edu

Locations

University of Iowa Hospitals & Clinics Department of Ophthalmology & Visual Sciences

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Christine A Sinkey, BSN, CCRC

3193538723christine-sinkey@uiowa.edu

Principal Investigator:

Elliott H Sohn, MD

More Information

Sponsor

University of Iowa

Last update posted

Apr 2, 2026

Last verified

Mar, 2026

Keywords

  • Active choroidal neovascularization (CNV)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Iowa on 2026-04-02.