Non-Responsive Diabetic Macular Edema and Spironolactone

Non-Responsive Diabetic Macular Edema in Patients With Pachychoroid and Choroidal Hyperpermeability.

Diabetic patients with macular edema and choroidal hyperpermeability (as manifested as a thick choroid on OCT (optical coherence tomography) and ICG hyperfluorescence on ICG) unresponsive to anti-VEGF (vascular endothelial growth factor) and steroid injections will be treated with spironolactone in addition to the continued treatment of anti-VEGF injections, specifically aflibercept (Eylea).

Study Overview

• Status: Withdrawn
• Conditions: Diabetic Maculopathy
• Intervention / Treatment: Drug: Spironolactone 50 mg

Detailed Description

This is a non-randomized, prospective study of 10 patients referred during the years 2018 to 2020 with the diagnosis of Diabetic Macular Edema. Each patient was noted to have pachychoroid, choroidal hyperpermeability, and most important resistant to multiple anti-VEGF and steroid intravitreal injections, and have moderate vision loss. In addition, despite the fact that we use anti-VEGF medications, we do not know the levels of VEGF in the eye, nor do we have an explanation for the inability to respond to these drugs. This study will determine the degree of VEGF concentrations, response to anti-VEGF treatments, and determine biomarkers of inflammation as a means for explaining the cause of treatment resistance. Subsequently, another pathological process will be treated with spironolactone to see if the degree of contribution of choroidal hyperpermeability to the exudative process.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion:

1. Presence of persistent Diabetic cystoid macular edema despite course of anti-VEGF injections and intraocular steroids. At the time of study baseline, the patients must be on q4 week intravitreal anti-VEGF medications and have failed (poor response - less than 50% decrease in macular central subfield thickness (CST) and volume) with intravitreal steroids (triamcinolone acetonide or dexamethasone implant).
2. Evidence of pachychoroid (choroid greater than 300 microns on OCT - EDI) with pachyvessels on OCT or OCTA. In addition, ICG (Indocyanine Green Angiogram) must show evidence of hyperfluorescence.
3. Visual Acuity of 20/25 to 20/400 at screening and baseline visits using an autorefractor or Early Treatment Diabetic Retinopathy Study (ETDRS).
4. IOP ≤ 25 mmHg - Patients that screen fail due to elevated IOP ˃25 mmHg may rescreen once IOP is treated and within normal limits (≤25 mmHg).

Exclusion:

1. Exudative maculopathies due to myopic choroidal degeneration, histoplasmosis, trauma, and specifically, the presence of angioid streaks.
2. Myocardial infarction or cerebrovascular accident within the last 6 weeks
3. Previous vitrectomy
4. Hypokalemia
5. Optic neuropathy
6. Traction maculopathies

7. Allergies to fluorescein and indocyanine, dilating agents, spironolactone, triamcinolone or anti-VEGF medications

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Spironolactone Treatment; Patients with non-responsive Diabetic Macular Edema will be treated with Spironolactone in addition to the regular course of monthly aflibercept (Eylea).	Drug: Spironolactone 50 mg; Add Spironolactone 50 mg to previous regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of eyes with complete reabsorption of intraretinal fluid		1 year
Macular Edema - Central Subgroup Thickening		1 year
Macular Edema - Volume	Macular volume	1 year
Vision, best corrected, logMAR units		1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Extrafoveal exudation (nCST)	1 year

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Mark H Nelson, MD MBA, Wake Forest University Health Sciences

Publications and helpful links

General Publications

• Kim DY, Lee JY, Lee EK, Kim JY. COMPARISON OF VISUAL/ANATOMICAL OUTCOMES AND RECURRENCE RATE BETWEEN ORAL SPIRONOLACTONE AND PHOTODYNAMIC THERAPY FOR NONRESOLVING CENTRAL SEROUS CHORIORETINOPATHY. Retina. 2020 Jun;40(6):1191-1199. doi: 10.1097/IAE.0000000000002507.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2022
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): August 2, 2022
• Last Update Submitted That Met QC Criteria: July 28, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Eylea; spironolactone; aflibercept; anti-VEGF injections
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone
• Other Study ID Numbers: IRB00073697

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Available upon request.
• IPD Sharing Time Frame: 12 months after completion date
• IPD Sharing Access Criteria: Contact Principal investigator
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No