Clinical trial NCT02354170: Short-Term Oral Mifepristone for Central Serous Chorioretinopathy
Official title: Short-Term Oral Mifepristone for Central Serous Chorioretinopathy. A Placebo-controlled Dose Ranging Study of Mifepristone in the Treatment of CSC (STOMP-CSC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Central Serous Chorioretinopathy
Keywords: Central Serous Chorioretinopathy, CSC
Lead sponsor: Bay Area Retina Associates
Sponsor class: OTHER
Collaborators: name: Ophthalmic Consultants of Boston
First posted: 2015-02-03
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of the study is to assess the efficacy and safety of mifepristone 300 or 900-mg once-daily dosing by mouth for 4 weeks in patients with central serous chorioretinopathy.

Detailed description: * Prospective, randomized, double-masked, placebo-controlled dose-ranging study
* Eligible patients will be those with CSC, with symptoms of blurred or distorted vision, with the presence of sub-retinal fluid as documented on optical coherence tomography (OCT) in the central foveal sub-field
* Only one eye of a participant will be included in the study, although both eyes will be evaluated. In patients with bilateral CSC, the eye with more sub-foveal fluid on OCT will be the study eye.
* Patients will be evaluated and treated at one of two study centers:

Ophthalmic Consultants of Boston (OCB), 50 Staniford St., Suite 600, Boston, MA

Bay Area Retina Associates (BARA), 122 La Casa Via, Suite 223, Walnut Creek, CA

* All participants will receive a standard ophthalmic examination as well as fluorescein and indocyanine green angiography and macular OCT per protocol.
* 30 patients will be enrolled, as follows:

  10 patients will be randomly assigned to Cohort 1, and will take one (1) mifepristone 300-mg tablet (300 mg total dose) once daily by mouth for 4 weeks.

  10 patients will be randomly assigned to Cohort 2, and will take three (3) mifepristone 300-mg tablet (900 mg total dose) once daily by mouth for 4 weeks.

  10 patients will be randomly assigned to Cohort 3, and will take placebo tablet(s) once daily by mouth for 4 weeks.
* After completing the enrollment criteria, a subject will be randomized 1:1:1 to Cohort 1, 2, or 3.
* During the Baseline visit and at the Week 2, 4, and 8 visits, all subjects will have laboratory testing of the following lab tests: serum electrolytes, BUN and creatinine, liver function tests
* Prior to initiating dosing of the study drug, all women of child-bearing potential (WOCBP) will have a serum beta-HCG assessed to rule out pregnancy; all WOCBP who are enrolled in the study will be required to use barrier contraception throughout the study.
* Adverse events will be tracked at each visit (see "Data Safety and Monitoring Plan" below)

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of central serous chorioretinopathy (CSC) with symptoms 6 weeks or prior documented episodes of sub-retinal fluid; patients who have had previous treatment for CSC may be included
2. Presence of sub-retinal fluid as documented on optical coherence tomography (OCT) in the central foveal sub-field
3. Age 18 or over
4. Willing and able to comply with clinic visits and study-related procedures
5. Ability to give written informed consent

Exclusion Criteria:

1. Age less than 18
2. Persons with impaired decision-making ability.
3. Women who are known to be breast-feeding, pregnant or are actively trying to conceive.
4. Additional eye disease affecting the macula, posterior retina, or ocular media that would limit or prevent the acquisition of OCT and angiographic images.
5. At screening, serum potassium \< LLN, BUN \> 1.5 ULN, serum creatinine \>1.5 ULN, AST \> 1.5 ULN, ALT \>1.5 ULN, bilirubin \> 1.5 ULN, alkaline phosphatase \> 1.5 ULN, serum albumin \>1.5 ULN or \<LLN.
6. Intraocular surgery (including cataract surgery) in the study eye within 60 days preceding baseline.
7. Active intraocular inflammation (grade trace or above) in the study eye.
8. Patients taking simvastatin, lovastatin, and CYP3A substrates with narrow therapeutic ranges, such as cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.
9. Patients who require concomitant treatment with systemic corticosteroids for serious medical conditions or illnesses (e.g., immunosuppression after organ transplantation).
10. Women with a history of unexplained vaginal bleeding and women with endometrial hyperplasia with atypia or endometrial carcinoma.
11. Patients with prior hypersensitivity reactions to mifepristone or to any of the product components.
12. Patients with known hypersensitivity to fluorescein or indocyanine green dyes.

    * WOCBP must be willing to practice adequate contraception during the study (adequate contraceptive measures include intrauterine device \[IUD\]; bilateral tubal ligation; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly). Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Primary outcomes:
measure: Resolution of Sub-retinal Fluid
timeFrame: 4 weeks after treatment
Secondary outcomes:
measure: Change in sub-retinal fluid and/or intraretinal fluid
timeFrame: Week 1, 2, 4, and 8
measure: Best Corrected Visual Acuity
timeFrame: Week 1, 2, 4, and 8
measure: Change in macular thickness
timeFrame: Week 1, 2, 4, and 8
measure: Change in foveal thickness
timeFrame: Week 1, 2, 4, and 8
measure: Change in choroidal thickness
timeFrame: Week 1, 2, 4, and 8
measure: Dye leakage in vasculature
timeFrame: Week 4 and 8
measure: Change in OCT characteristics in the fellow eye
timeFrame: Week 8
measure: Proportion of acute vs. chronic CSC patients
timeFrame: Week 8
measure: Safety and Tolerability Characteristics
timeFrame: Week 8
Other outcomes:
Locations:
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates
state: California
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
Study officials:
affiliation: Bay Area Retina Associates
name: Roger A Goldberg, M.D., MBA
role: PRINCIPAL_INVESTIGATOR
affiliation: Ophthalmic Consultants of Boston
name: Jeffrey S Heier, M.D.
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: Tittl MK, Spaide RF, Wong D, Pilotto E, Yannuzzi LA, Fisher YL, Freund B, Guyer DR, Slakter JS, Sorenson JA. Systemic findings associated with central serous chorioretinopathy. Am J Ophthalmol. 1999 Jul;128(1):63-8. doi: 10.1016/s0002-9394(99)00075-6.
citation: Yannuzzi LA. Type-A behavior and central serous chorioretinopathy. Retina. 1987 Summer;7(2):111-31. doi: 10.1097/00006982-198700720-00009.
citation: Spaide RF, Campeas L, Haas A, Yannuzzi LA, Fisher YL, Guyer DR, Slakter JS, Sorenson JA, Orlock DA. Central serous chorioretinopathy in younger and older adults. Ophthalmology. 1996 Dec;103(12):2070-9; discussion 2079-80. doi: 10.1016/s0161-6420(96)30386-2.
citation: Ross A, Ross AH, Mohamed Q. Review and update of central serous chorioretinopathy. Curr Opin Ophthalmol. 2011 May;22(3):166-73. doi: 10.1097/ICU.0b013e3283459826.
citation: Castro-Correia J, Coutinho MF, Rosas V, Maia J. Long-term follow-up of central serous retinopathy in 150 patients. Doc Ophthalmol. 1992;81(4):379-86. doi: 10.1007/BF00169099.
citation: Gilbert CM, Owens SL, Smith PD, Fine SL. Long-term follow-up of central serous chorioretinopathy. Br J Ophthalmol. 1984 Nov;68(11):815-20. doi: 10.1136/bjo.68.11.815.
citation: Bujarborua D. Long-term follow-up of idiopathic central serous chorioretinopathy without laser. Acta Ophthalmol Scand. 2001 Aug;79(4):417-21. doi: 10.1034/j.1600-0420.2001.079004417.x.
citation: Folk JC, Thompson HS, Han DP, Brown CK. Visual function abnormalities in central serous retinopathy. Arch Ophthalmol. 1984 Sep;102(9):1299-302. doi: 10.1001/archopht.1984.01040031049021.
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: Spitznas M, Huke J. Number, shape, and topography of leakage points in acute type I central serous retinopathy. Graefes Arch Clin Exp Ophthalmol. 1987;225(6):437-40. doi: 10.1007/BF02334172.
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: Montero JA, Ruiz-Moreno JM. Optical coherence tomography characterisation of idiopathic central serous chorioretinopathy. Br J Ophthalmol. 2005 May;89(5):562-4. doi: 10.1136/bjo.2004.049403.
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: 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: Ficker L, Vafidis G, While A, Leaver P. Long-term follow-up of a prospective trial of argon laser photocoagulation in the treatment of central serous retinopathy. Br J Ophthalmol. 1988 Nov;72(11):829-34. doi: 10.1136/bjo.72.11.829.
citation: Taban M, Boyer DS, Thomas EL, Taban M. Chronic central serous chorioretinopathy: photodynamic therapy. Am J Ophthalmol. 2004 Jun;137(6):1073-80. doi: 10.1016/j.ajo.2004.01.043.
citation: Inoue R, Sawa M, Tsujikawa M, Gomi F. Association between the efficacy of photodynamic therapy and indocyanine green angiography findings for central serous chorioretinopathy. Am J Ophthalmol. 2010 Mar;149(3):441-6.e1-2. doi: 10.1016/j.ajo.2009.10.011.
citation: Maruko I, Iida T, Sugano Y, Ojima A, Ogasawara M, Spaide RF. Subfoveal choroidal thickness after treatment of central serous chorioretinopathy. Ophthalmology. 2010 Sep;117(9):1792-9. doi: 10.1016/j.ophtha.2010.01.023. Epub 2010 May 15.
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: Shin JY, Woo SJ, Yu HG, Park KH. Comparison of efficacy and safety between half-fluence and full-fluence photodynamic therapy for chronic central serous chorioretinopathy. Retina. 2011 Jan;31(1):119-26. doi: 10.1097/IAE.0b013e3181e378f2.
citation: Golshahi A, Klingmuller D, Holz FG, Eter N. Ketoconazole in the treatment of central serous chorioretinopathy: a pilot study. Acta Ophthalmol. 2010 Aug;88(5):576-81. doi: 10.1111/j.1755-3768.2008.01467.x. Epub 2009 May 12.
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: Avci R, Deutman AF. [Treatment of central serous choroidopathy with the beta receptor blocker metoprolol (preliminary results)]. Klin Monbl Augenheilkd. 1993 Mar;202(3):199-205. doi: 10.1055/s-2008-1045583. German.
citation: Tatham A, Macfarlane A. The use of propranolol to treat central serous chorioretinopathy: an evaluation by serial OCT. J Ocul Pharmacol Ther. 2006 Apr;22(2):145-9. doi: 10.1089/jop.2006.22.145.
citation: Pikkel J, Beiran I, Ophir A, Miller B. Acetazolamide for central serous retinopathy. Ophthalmology. 2002 Sep;109(9):1723-5. doi: 10.1016/s0161-6420(02)01157-0.
citation: Davis KL, Nappi JM. The cardiovascular effects of eplerenone, a selective aldosterone-receptor antagonist. Clin Ther. 2003 Nov;25(11):2647-68. doi: 10.1016/s0149-2918(03)80326-0.
citation: McCurley A, Jaffe IZ. Mineralocorticoid receptors in vascular function and disease. Mol Cell Endocrinol. 2012 Mar 24;350(2):256-65. doi: 10.1016/j.mce.2011.06.014. Epub 2011 Jun 24.
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: 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: Krum H, Nolly H, Workman D, He W, Roniker B, Krause S, Fakouhi K. Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients. Hypertension. 2002 Aug;40(2):117-23. doi: 10.1161/01.hyp.0000025146.19104.fe.
citation: Flack JM, Oparil S, Pratt JH, Roniker B, Garthwaite S, Kleiman JH, Yang Y, Krause SL, Workman D, Saunders E. Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients. J Am Coll Cardiol. 2003 Apr 2;41(7):1148-55. doi: 10.1016/s0735-1097(03)00054-8.