Eplerenone for Central Serous Chorioretinopathy

Central Serous Chorioretinopathy Clinical Trial

Official title:

Eplerenone for Central Serous Chorioretinopathy: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01822561
• Other study ID #: NEEC-10722
• Status: Completed
• Phase: Phase 2
• Start date: May 2013
• Est. completion date: December 2017

Study information

• Verified date: April 2018
• Source: Tufts Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: December 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Central Serous Chorioretinopathy

Intervention

Drug:
• Eplerenone 50mg
All patients will receive the same dose of eplerenone.

Locations

Country	Name	City	State
United States	New England Eye Center / Tufts Medical Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Tufts Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (12)

Bouzas EA, Karadimas P, Pournaras CJ. Central serous chorioretinopathy and glucocorticoids. Surv Ophthalmol. 2002 Sep-Oct;47(5):431-48. Review. — View Citation

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. — View Citation

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. — View Citation

Fujimoto H, Gomi F, Wakabayashi T, Sawa M, Tsujikawa M, Tano Y. Morphologic changes in acute central serous chorioretinopathy evaluated by fourier-domain optical coherence tomography. Ophthalmology. 2008 Sep;115(9):1494-500, 1500.e1-2. doi: 10.1016/j.opht — View Citation

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. — View Citation

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. — View Citation

Nielsen JS, Jampol LM. Oral mifepristone for chronic central serous chorioretinopathy. Retina. 2011 Oct;31(9):1928-36. doi: 10.1097/IAE.0b013e31821c3ef6. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Baseline and 1 month after treatment
Secondary	Change in Macular Thickness	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.	Baseline and 1 month after treatment
Secondary	Change in Best Corrected Visual Acuity	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)	Baseline and 1 month after treatment
Secondary	Change in Subfoveal Choroidal Thickness, Study Eye	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.	Baseline and 1 month after treatment
Secondary	Change in Serum Potassium	Eplerenone can cause elevation of serum potassium. After initial screening, serum potassium was evaluated at 1 and 4 weeks after baseline.	Baseline and 1 month after treatment