Short-Term Oral Mifepristone for Central Serous Chorioretinopathy

Central Serous Chorioretinopathy Clinical Trial

— STOMP-CSC  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02354170
• Other study ID #: STOMP-CSC
• Status: Completed
• Phase: Phase 2
• First received: January 29, 2015
• Last updated: July 24, 2017
• Start date: January 2015
• Est. completion date: April 27, 2017

Study information

• Verified date: July 2017
• Source: Bay Area Retina Associates
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 27, 2017
• Est. primary completion date: April 27, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Central Serous Chorioretinopathy

Intervention

Drug:
• Mifepristone

• Placebo

Locations

Country	Name	City	State
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Bay Area Retina Associates	Walnut Creek	California

Sponsors (2)

Lead Sponsor	Collaborator
Roger Goldberg, M.D., MBA	Ophthalmic Consultants of Boston

Country where clinical trial is conducted

United States, 

References & Publications (35)

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. German. — View Citation

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

Bujarborua D. Long-term follow-up of idiopathic central serous chorioretinopathy without laser. Acta Ophthalmol Scand. 2001 Aug;79(4):417-21. — View 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. — 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

Davis KL, Nappi JM. The cardiovascular effects of eplerenone, a selective aldosterone-receptor antagonist. Clin Ther. 2003 Nov;25(11):2647-68. Review. — View 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. — View 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. — View Citation

Folk JC, Thompson HS, Han DP, Brown CK. Visual function abnormalities in central serous retinopathy. Arch Ophthalmol. 1984 Sep;102(9):1299-302. — 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.ophtha.2008.01.021. Epub 2008 Apr 18. — 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

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. — View Citation

Golshahi A, Klingmüller 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. — 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

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. — View 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. — View 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. — View 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. Review. — View Citation

Montero JA, Ruiz-Moreno JM. Optical coherence tomography characterisation of idiopathic central serous chorioretinopathy. Br J Ophthalmol. 2005 May;89(5):562-4. — 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

Pikkel J, Beiran I, Ophir A, Miller B. Acetazolamide for central serous retinopathy. Ophthalmology. 2002 Sep;109(9):1723-5. — 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

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. Review. — View 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. — View 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. — View 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. — View Citation

Taban M, Boyer DS, Thomas EL, Taban M. Chronic central serous chorioretinopathy: photodynamic therapy. Am J Ophthalmol. 2004 Jun;137(6):1073-80. — View 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. — View 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. — 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

Yannuzzi LA. Type-A behavior and central serous chorioretinopathy. Retina. 1987 Summer;7(2):111-31. Review. — 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 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Resolution of Sub-retinal Fluid	Presence or absence of subretinal fluid on spectral-domain OCT after 4 weeks of treatment with mifepristone 300 or 900 mg daily, compared with placebo.	4 weeks after treatment
Secondary	Change in sub-retinal fluid and/or intraretinal fluid	Change compared to Baseline in subretinal fluid and/or intraretinal fluid on OCT at Week 1, 2, 4, and 8,	Week 1, 2, 4, and 8
Secondary	Best Corrected Visual Acuity	Change compared to Baseline in ETDRS BCVA at Week 1, 2, 4, and 8.	Week 1, 2, 4, and 8
Secondary	Change in macular thickness	Change compared to Baseline in central macular circle thickness on OCT, automatically calculated with OCT software at Week 1, 2, 4, and 8.	Week 1, 2, 4, and 8
Secondary	Change in foveal thickness	Change compared to Baseline in thickness of subretinal fluid under the fovea on OCT, manually calculated at Week 1, 2, 4, and 8	Week 1, 2, 4, and 8
Secondary	Change in choroidal thickness	Change compared to Baseline in thickness of choroid under the fovea on enhanced-depth imaging OCT, manually calculated, at Week 1, 2, 4, and 8.	Week 1, 2, 4, and 8
Secondary	Dye leakage in vasculature	Change compared to Baseline in dye leakage characteristics on fluorescein and indocyanine green angiography at Week 4 and Week 8.	Week 4 and 8
Secondary	Change in OCT characteristics in the fellow eye	Change compared to Baseline in the same OCT characteristics listed above, in the fellow eye.	Week 8
Secondary	Proportion of acute vs. chronic CSC patients	Proportion of acute versus chronic CSC patients as determined at Baseline, with the above outcomes analyzed for each sub-group.	Week 8
Secondary	Safety and Tolerability Characteristics	Safety and tolerability characteristics in this patient population via clinical laboratory data and adverse events	Week 8