Clinical trial NCT01822561: Eplerenone for Central Serous Chorioretinopathy
Official title: Eplerenone for Central Serous Chorioretinopathy: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Central Serous Chorioretinopathy
Keywords: Central Serous Chorioretinopathy
Eplerenone
Optical Coherence Tomography
Enhanced Depth Imaging
Subretinal Fluid
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
First posted: 2013-04-02
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Complete Resolution of Subretinal Fluid
timeFrame: Baseline and 1 month after treatment
Secondary outcomes:
measure: Change in Macular Thickness
timeFrame: Baseline and 1 month after treatment
measure: Change in Best Corrected Visual Acuity
timeFrame: Baseline and 1 month after treatment
measure: Change in Subfoveal Choroidal Thickness, Study Eye
timeFrame: Baseline and 1 month after treatment
measure: Change in Serum Potassium
timeFrame: Baseline and 1 month after treatment
Other outcomes:
Locations:
city: Boston
country: United States
facility: New England Eye Center / Tufts Medical Center
state: Massachusetts
Study officials:
affiliation: Tufts Medical Center
name: Andre J Witkin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhao M, Celerier 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.
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.
citation: Bouzas EA, Karadimas P, Pournaras CJ. Central serous chorioretinopathy and glucocorticoids. Surv Ophthalmol. 2002 Sep-Oct;47(5):431-48. doi: 10.1016/s0039-6257(02)00338-7.
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.
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.
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.
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. doi: 10.1016/0002-9394(83)90265-9.
citation: Nielsen JS, Jampol LM. Oral mifepristone for chronic central serous chorioretinopathy. Retina. 2011 Oct;31(9):1928-36. doi: 10.1097/IAE.0b013e31821c3ef6.
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.
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. doi: 10.1016/s0895-7061(02)02957-6.
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. doi: 10.1056/NEJMoa030207. Epub 2003 Mar 31.
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.ophtha.2008.01.021. Epub 2008 Apr 18.
citation: Moein HR, Bierman LW, Novais EA, Moreira-Neto C, Baumal CR, Rogers A, Duker JS, Witkin AJ. Short-term eplerenone for treatment of chronic central serous chorioretinopathy; a prospective study. Int J Retina Vitreous. 2019 Sep 9;5:39. doi: 10.1186/s40942-019-0190-y. eCollection 2019.