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Exudative Macular DegenerationPhase 2NCT04504123

MMP-9 Inhibition for Recalcitrant Wet AMD

A Phase 2 study testing Doxycycline Hyclate in people with Exudative Macular Degeneration and Wet Age-related Macular Degeneration, run by University of Iowa at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 50 to 99 years
What is being tested?
Doxycycline Hyclate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
50 participants
Where
1 siteUnited States
Study dates
4 Nov 2020to 1 Mar 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 50 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
Show all 26Show fewer
  • 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.
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Elliott H Sohn, MD contact

3193563285

elliott-sohn@uiowa.edu

United States1 site, 1 recruiting

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

    Iowa City, Iowa, 52242

    Christine A Sinkey, BSN, CCRC, 3193538723, christine-sinkey@uiowa.edu

    Elliott H Sohn, MD

    Recruiting

Other trials in United States

About this study

Official title: MMP-9 Inhibition for Recalcitrant Wet Age-Related Macular Degeneration (AMD)

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.

Read the 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.

Being tested
Doxycycline Hyclate, Placebo
Keywords
Active choroidal neovascularization (CNV)
Medical subject headings
Wet Macular Degeneration

What participants receive

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

  • Doxycycline HyclateDrug

    Also called Antibiotic - tetracycline compound

    Doxycycline Hyclate capsules, USP 50 mg

  • PlaceboDrug

    Also called Inactive substance

    Placebo

Study groups in NCT04504123
Study groupRoleWhat they receive
DoxycyclineExperimentalParticipants received doxycycline hyclate 50 mg capsule orally once a day for 6 months
Receives: Drug: Doxycycline Hyclate
PlaceboPlacebo comparatorParticipants received placebo (inactive) capsule orally once a day for 6 months
Receives: Drug: Placebo

What is being measured

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

  1. Resolution of the persistent retinal fluid on optical coherence tomography (OCT)

    percentage of patients with retinal fluid-free status

    Measured: 9 months

Secondary outcomes (4)

  1. Change in optical coherence tomography (OCT) central media thickness (CMT)

    mean change in central media thickness

    Measured: 9 months compared to baseline

  2. Change in best corrected visual acuity (BCVA)

    mean change in logMAR / percentage of patients with a gain or loss of more than 5 ETDRS letters

    Measured: 6 months and 9 months compared to Baseline

  3. Number of intravitreal injections (IVI) administered

    total number of anti-VEGF intravitreal injections

    Measured: 6 months and 9 months

  4. Inflammatory mediators matrix metalloproteinases MMP-9 and MMP-9 activity

    anterior eye aqueous fluid and blood plasma

    Measured: Baseline, 6 months and 9 months

Timeline

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

  1. First posted7 Aug 2020
  2. Study start4 Nov 2020
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion1 Mar 2027 (estimated)

Resources

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
Model description
Doxycycline Hyclate 50 mg versus placebo capsule
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04504123
Sponsor's protocol ID
202001041
Status last verified
Mar 2026
First submitted
4 Aug 2020
Last updated
2 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: The investigators do not plan to share the data with other researchers

Publications

  • Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014 Feb;2(2):e106-16. doi: 10.1016/S2214-109X(13)70145-1. Epub 2014 Jan 3.

    PubMed 25104651

  • Ferris FL 3rd, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984 Nov;102(11):1640-2. doi: 10.1001/archopht.1984.01040031330019.

    PubMed 6208888

  • Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1419-31. doi: 10.1056/NEJMoa054481.

    PubMed 17021318

  • Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1432-44. doi: 10.1056/NEJMoa062655.

    PubMed 17021319

  • Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group; Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE, Toth C, Redford M, Ferris FL 3rd. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012 Jul;119(7):1388-98. doi: 10.1016/j.ophtha.2012.03.053. Epub 2012 May 1.

    PubMed 22555112

  • Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U; VIEW 1 and VIEW 2 Study Groups. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012 Dec;119(12):2537-48. doi: 10.1016/j.ophtha.2012.09.006. Epub 2012 Oct 17.

    PubMed 23084240

  • Arnold JJ, Campain A, Barthelmes D, Simpson JM, Guymer RH, Hunyor AP, McAllister IL, Essex RW, Morlet N, Gillies MC; Fight Retinal Blindness Study Group. Two-year outcomes of "treat and extend" intravitreal therapy for neovascular age-related macular degeneration. Ophthalmology. 2015 Jun;122(6):1212-9. doi: 10.1016/j.ophtha.2015.02.009. Epub 2015 Apr 4.

    PubMed 25846847

  • Brown DM, Regillo CD. Anti-VEGF agents in the treatment of neovascular age-related macular degeneration: applying clinical trial results to the treatment of everyday patients. Am J Ophthalmol. 2007 Oct;144(4):627-37. doi: 10.1016/j.ajo.2007.06.039.

    PubMed 17893015

  • Krebs I, Glittenberg C, Ansari-Shahrezaei S, Hagen S, Steiner I, Binder S. Non-responders to treatment with antagonists of vascular endothelial growth factor in age-related macular degeneration. Br J Ophthalmol. 2013 Nov;97(11):1443-6. doi: 10.1136/bjophthalmol-2013-303513. Epub 2013 Aug 21.

    PubMed 23966368

  • Barthelmes D, Walton R, Campain AE, Simpson JM, Arnold JJ, McAllister IL, Guymer RH, Hunyor AP, Essex RW, Morlet N, Gillies MC; Fight Retinal Blindness! Project Investigators. Outcomes of persistently active neovascular age-related macular degeneration treated with VEGF inhibitors: observational study data. Br J Ophthalmol. 2015 Mar;99(3):359-64. doi: 10.1136/bjophthalmol-2014-305514. Epub 2014 Sep 23.

    PubMed 25249615

  • Ersoy L, Ristau T, Kirchhof B, Liakopoulos S. Response to anti-VEGF therapy in patients with subretinal fluid and pigment epithelial detachment on spectral-domain optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2014 Jun;252(6):889-97. doi: 10.1007/s00417-013-2519-9. Epub 2013 Nov 26.

    PubMed 24271025

  • Keane PA, Liakopoulos S, Ongchin SC, Heussen FM, Msutta S, Chang KT, Walsh AC, Sadda SR. Quantitative subanalysis of optical coherence tomography after treatment with ranibizumab for neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3115-20. doi: 10.1167/iovs.08-1689. Epub 2008 Apr 11.

    PubMed 18408176

  • Forooghian F, Cukras C, Meyerle CB, Chew EY, Wong WT. Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration. Retina. 2009 Jun;29(6):723-31. doi: 10.1097/IAE.0b013e3181a2c1c3.

    PubMed 19516114

  • Brown DM, Tuomi L, Shapiro H; Pier Study Group. Anatomical measures as predictors of visual outcomes in ranibizumab-treated eyes with neovascular age-related macular degeneration. Retina. 2013 Jan;33(1):23-34. doi: 10.1097/IAE.0b013e318263cedf.

    PubMed 23073338

  • van der Reis MI, La Heij EC, De Jong-Hesse Y, Ringens PJ, Hendrikse F, Schouten JS. A systematic review of the adverse events of intravitreal anti-vascular endothelial growth factor injections. Retina. 2011 Sep;31(8):1449-69. doi: 10.1097/IAE.0b013e3182278ab4.

    PubMed 21817960

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Doxycycline Hyclate in people with Exudative Macular Degeneration and Wet Age-related Macular Degeneration, run by University of Iowa 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 4 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 2 Apr 2026. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Elliott H Sohn, MD (3193563285, elliott-sohn@uiowa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Resolution of the persistent retinal fluid on optical coherence tomography (OCT) (time frame: 9 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 NCT04504123, which also lists 69 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 2 Apr 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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