Eplerenone for Central Serous Chorioretinopathy

• Sponsor: Tufts Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01822561
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arm: 1
• Actual Duration (Months): 55
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Central Serous Chorioretinopathy	Drug: Eplerenone 50mg	Phase 2

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Eplerenone for Central Serous Chorioretinopathy: A Pilot Study
• Actual Study Start Date: May 1, 2013
• Actual Primary Completion Date: Apr 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eplerenone All patients in this study will receive Eplerenone 50mg once daily for 4 weeks.	Drug: Eplerenone 50mg; All patients will receive the same dose of eplerenone.; Other Names: Inspra (Pfizer) Eplerenone (Generic)

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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)

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New England Eye Center / Tufts Medical Center	Boston	Massachusetts	United States	02111

Sponsors and Collaborators

• Tufts Medical Center

Investigators

• Principal Investigator: Andre J Witkin, MD, Tufts Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 10, 2013

More Information

Publications

• Bouzas EA, Karadimas P, Pournaras CJ. Central serous chorioretinopathy and glucocorticoids. Surv Ophthalmol. 2002 Sep-Oct;47(5):431-48. Review.
• Chan WM, Lai TY, Lai RY, Liu DT, Lam DS. Half-dose verteporfin photodynamic therapy for acute central serous chorioretinopathy: one-year results of a randomized controlled trial. Ophthalmology. 2008 Oct;115(10):1756-65. doi: 10.1016/j.ophtha.2008.04.014. Epub 2008 Jun 5.
• Forooghian F, Meleth AD, Cukras C, Chew EY, Wong WT, Meyerle CB. Finasteride for chronic central serous chorioretinopathy. Retina. 2011 Apr;31(4):766-71. doi: 10.1097/IAE.0b013e3181f04a35.
• Gemenetzi M, De Salvo G, Lotery AJ. Central serous chorioretinopathy: an update on pathogenesis and treatment. Eye (Lond). 2010 Dec;24(12):1743-56. doi: 10.1038/eye.2010.130. Epub 2010 Oct 8. Review.
• Imamura Y, Fujiwara T, Margolis R, Spaide RF. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina. 2009 Nov-Dec;29(10):1469-73. doi: 10.1097/IAE.0b013e3181be0a83.
• Nielsen JS, Jampol LM. Oral mifepristone for chronic central serous chorioretinopathy. Retina. 2011 Oct;31(9):1928-36. doi: 10.1097/IAE.0b013e31821c3ef6.
• Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 Apr 3;348(14):1309-21. Epub 2003 Mar 31. Erratum in: N Engl J Med. 2003 May 29;348(22):2271.
• Reibaldi M, Cardascia N, Longo A, Furino C, Avitabile T, Faro S, Sanfilippo M, Russo A, Uva MG, Munno F, Cannemi V, Zagari M, Boscia F. Standard-fluence versus low-fluence photodynamic therapy in chronic central serous chorioretinopathy: a nonrandomized clinical trial. Am J Ophthalmol. 2010 Feb;149(2):307-315.e2. doi: 10.1016/j.ajo.2009.08.026. Epub 2009 Nov 6.
• Robertson DM, Ilstrup D. Direct, indirect, and sham laser photocoagulation in the management of central serous chorioretinopathy. Am J Ophthalmol. 1983 Apr;95(4):457-66.
• Weinberger MH, Roniker B, Krause SL, Weiss RJ. Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am J Hypertens. 2002 Aug;15(8):709-16.
• Zhao M, Célérier I, Bousquet E, Jeanny JC, Jonet L, Savoldelli M, Offret O, Curan A, Farman N, Jaisser F, Behar-Cohen F. Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy. J Clin Invest. 2012 Jul;122(7):2672-9. doi: 10.1172/JCI61427. Epub 2012 Jun 11.

• Responsible Party: Tufts Medical Center
• ClinicalTrials.gov Identifier: NCT01822561
• Other Study ID Numbers: NEEC-10722
• First Posted: Apr 2, 2013
• Last Update Posted: May 16, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Tufts Medical Center: Central Serous Chorioretinopathy; Eplerenone; Optical Coherence Tomography; Enhanced Depth Imaging; Subretinal Fluid
• Additional relevant MeSH terms: Central Serous Chorioretinopathy; Eplerenone

Study Results

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.

Arm/Group Title	Eplerenone Group
Arm/Group Description	All patients in this study received Eplerenone 50mg once daily for 4 weeks. Eplerenone 50mg: All patients received the same dose of eplerenone.
Period Title: Overall Study
STARTED	15
COMPLETED	13
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	CSCR Patients Who Received Eplerenone
Arm/Group Description	All patients were diagnosed with central serous chorioretinopathy. All patients received 50mg oral eplerenone daily for 4 weeks.
Overall Participants	13
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.6 (2.3)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	13 100%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
United States	13 100%
Patients with chronic CSCR (Count of Participants)
Count of Participants [Participants]	11 84.6%

Outcome Measures

1. Primary Outcome

Title	Complete Resolution of Subretinal Fluid
Description	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
Time Frame	Baseline and 1 month after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients That Took Eplerenone
Arm/Group Description	Patients received 50mg oral eplerenone daily for 1 month
Measure Participants	13
Number [participants]	0 0%

2. Secondary Outcome

Title	Change in Macular Thickness
Description	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.
Time Frame	Baseline and 1 month after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients That Received Eplerenone
Arm/Group Description	Patients took 50mg oral eplerenone daily for 1 month
Measure Participants	13
Mean (Standard Deviation) [Microns]	-26 (27)

3. Secondary Outcome

Title	Change in Best Corrected Visual Acuity
Description	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)
Time Frame	Baseline and 1 month after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients That Took Eplerenone
Arm/Group Description	Patients received oral Eplerenone 50mg once daily for 4 weeks.
Measure Participants	13
Mean (Standard Deviation) [logMAR]	-0.03 (0.08)

4. Secondary Outcome

Title	Change in Subfoveal Choroidal Thickness, Study Eye
Description	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.
Time Frame	Baseline and 1 month after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients That Received Eplerenone
Arm/Group Description	Patients received oral Eplerenone 50mg once daily for 4 weeks.
Measure Participants	13
Mean (Standard Deviation) [microns]	29.8 (18.5)

5. Secondary Outcome

Title	Change in Serum Potassium
Description	Eplerenone can cause elevation of serum potassium. After initial screening, serum potassium was evaluated at 1 and 4 weeks after baseline.
Time Frame	Baseline and 1 month after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients That Received Eplerenone
Arm/Group Description	Patients took oral Eplerenone 50mg once daily for 4 weeks.
Measure Participants	13
Mean (Standard Deviation) [mEq/L]	0.11 (0.09)

Adverse Events

Time Frame	3 months. Patients were followed for a minimum of 3 months after treatment was initiated.
Arm/Group Title	Eplerenone Group
Arm/Group Description	All patients had central serous chorioretinopathy and were treated with 50mg oral eplerenone once daily
All Cause Mortality
	Eplerenone Group
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Serious Adverse Events
	Eplerenone Group
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Eplerenone Group
	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)
Cardiac disorders
Palpitations	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Shortness of breath	1/15 (6.7%)	1

Limitations/Caveats

The study had limited enrollment due to lack of interest on the part of potential study subjects.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.