Eplerenone for Central Serous Chorioretinopathy

Eplerenone for Central Serous Chorioretinopathy: A Pilot Study

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01822561

Enrollment

Registered

2013-04-02

Start date

2013-05-31

Completion date

2017-12-31

Last updated

2018-05-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Central Serous Chorioretinopathy

Keywords

Central Serous Chorioretinopathy, Eplerenone, Optical Coherence Tomography, Enhanced Depth Imaging, Subretinal Fluid

Brief summary

* The goal of the study is to examine the short-term effects and safety of a systemic anti-aldosterone medication, eplerenone, in a small group of patients with central serous chorioretinopathy (CSCR). * There is currently no standard treatment or therapy for either acute or chronic CSCR, a potentially debilitating eye disease. * There is evidence in both animals and humans that high blood serum corticosteroid levels can cause or worsen CSCR or findings similar to CSCR in the choroid and retina * Eplerenone, a mineralocorticoid receptor antagonist, has been shown to be of visual and anatomic benefit in a small series of 4 patients with chronic CSCR, suggesting that decreasing mineralocorticoid action in the eye may improve signs and symptoms of CSCR * The investigators' aim is to evaluate a standardized dose of eplerenone in a controlled prospective fashion for both acute and chronic CSCR. * The study consists of taking a standard dose of eplerenone, 50mg once daily, for 1 month * Over the course of the month, patients will be monitored for side effects, as well as visual and anatomical response to the medication

Detailed description

* The investigators hypothesize that aldosterone inhibition with eplerenone will decrease choroidal vessel vasodilation, focal leakage, and choroidal thickness in patients with both acute and chronic CSCR, leading to resolution of subretinal fluid and ultimately an improvement in symptoms. * Resolution of sub-retinal fluid will be the primary outcome, which can be precisely measured using optical coherence tomography (OCT) * Secondary outcomes will include: Change in macular thickness measured with OCT, in central macular circle thickness on OCT, change in visual acuity, change in dye leakage characteristics on fluorescein angiography, change in OCT characteristics of the fellow eye, and safety and tolerability characteristics * In acute CSCR, subretinal fluid often resolves on its own, but it often takes several months (the literature shows that \ 20% of patients have complete resolution of sub-retinal fluid on OCT 1 month after presentation) * Chronic CSCR is defined as persistent fluid on OCT after 3 months of symptom onset, or recurrence of signs and symptoms within 1 year after the prior episode * In this study, the investigators will not make a distinction between acute and chronic CSCR * Eplerenone, a generic medication, is a potassium sparing diuretic, which is FDA approved to treat heart failure as well as high blood pressure, but is not FDA approved for treatment of central serous chorioretinopathy. * The most important side effect of eplerenone is elevation of serum potassium and decrease of blood pressure * Patients will therefore be screened with routine blood tests as suggested by the package insert of the medication, and serum potassium and blood pressure will be monitored routinely as directed by the medication package insert * Study visits will be performed at therapy initiation, 1 week, 2 weeks, and 4 weeks

Interventions

DRUGEplerenone 50mg

All patients will receive the same dose of eplerenone.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

1. Age 18 or over 2. Ability to give written informed consent 3. Presence of sub-retinal fluid under the fovea as seen on OCT 4. Diagnosis of Acute or Chronic CSCR: * Acute CSCR: First presentation to eye clinic with visual symptoms, including decreased vision or visual distortion, and the characteristic appearance of CSCR on examination, fluorescein angiography, and OCT. * Chronic CSCR: Previous diagnosis of CSCR, persistent subretinal fluid on OCT for more than 3 months after initial presentation to the eye clinic, and \<50% reduction in fluid thickness on OCT after 3 months. Patients who have had previous treatment for CSCR may be included.

Exclusion criteria

1. Age less than 18 2. Persons with impaired decision-making ability. 3. Women who are known to be pregnant or are actively trying to conceive. 4. Additional eye disease affecting the macula or posterior retina. 5. At screening, serum potassium concentration ≥5.0 mEq/L , a serum creatinine concentration \>2 mg/dL in men and \>1.8 mg/dL in women, or a creatinine clearance \<50 mL/min, and during concomitant administration of potassium supplements, potassium-sparing diuretics, and/or potent CYP3A4 inhibitors (amifostine, cyclosporine, fluconazole, itraconazole, ketoconazole, mifepristone, posaconazole, potassium salts, Rituximab, tacrolimus or voriconazole). 6. Patients with type 2 diabetes will be screened for microalbuminuria with a urinalysis. If microalbuminuria is present, these patients will be excluded.

Design outcomes

Primary

Measure	Time frame	Description
Complete Resolution of Subretinal Fluid	Baseline and 1 month after treatment	Optical coherence tomography is an imaging technique capable of extremely high resolution (\ 5-7 microns) imaging of the macula, and is able to detect the presence and amount of subretinal fluid present, the key anatomic abnormality in Central Serous Chorioretinopathy

Secondary

Measure	Time frame	Description
Change in Macular Thickness	Baseline and 1 month after treatment	Automated software to calculate the thickness of the macula is standard on commercial OCT devices. Macular thickness before and after treatment will be assessed and compared.
Change in Best Corrected Visual Acuity	Baseline and 1 month after treatment	Visual acuity will be measured with standard eye charts, with manifest refraction at the initiation and conclusion of treatment. Although an important measure, this was not chosen as the primary outcome measure, as some patients with central serous chorioretinopathy may have a normal visual acuity when properly refracted (refraction can change with elevation of the macula by sub-retinal fluid)
Change in Subfoveal Choroidal Thickness, Study Eye	Baseline and 1 month after treatment	Choroidal thickness can be measured using optical coherence tomography, and is known to be affected in patients with central serous chorioretinopathy. Thickness of the choroid under the fovea will be manually calculated in both the study eye.
Change in Serum Potassium	Baseline and 1 month after treatment	Eplerenone can cause elevation of serum potassium. After initial screening, serum potassium was evaluated at 1 and 4 weeks after baseline.

Countries

United States

Participant flow

Recruitment details

Patients with central serous chorioretinopathy were recruited in the ophthalmology clinic at Tufts Medical Center in Boston, MA between April 2013 and April 2017.

Participants by arm

Arm	Count
CSCR Patients Who Received Eplerenone All patients were diagnosed with central serous chorioretinopathy. All patients received 50mg oral eplerenone daily for 4 weeks.	13
Total	13

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	2

Baseline characteristics

Characteristic	CSCR Patients Who Received Eplerenone	—
Age, Continuous	55.6 years STANDARD_DEVIATION 2.3	—
Patients with chronic CSCR	11 Participants	—
Race and Ethnicity Not Collected	—	— Participants
Region of Enrollment United States	13 Participants	—
Sex: Female, Male Female	0 Participants	—
Sex: Female, Male Male	13 Participants	—

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 15
other Total, other adverse events	2 / 15
serious Total, serious adverse events	0 / 15

Outcome results

Primary

Complete Resolution of Subretinal Fluid

Optical coherence tomography is an imaging technique capable of extremely high resolution (\ 5-7 microns) imaging of the macula, and is able to detect the presence and amount of subretinal fluid present, the key anatomic abnormality in Central Serous Chorioretinopathy