Finasteride for Chronic Central Serous Chorioretinopathy

Retinal Disease Clinical Trial

Official title:

Phase II, Randomized, Placebo-Controlled Study for the Evaluation of Finasteride in the Treatment of Chronic Central Serous Chorioretinopathy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01585441
• Other study ID #: 120119
• Secondary ID: 12-EI-0119
• Status: Terminated
• Phase: Phase 2
• First received: April 24, 2012
• Last updated: November 25, 2014
• Start date: April 2012
• Est. completion date: December 2013

Study information

• Verified date: November 2014
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Background:

• Central serous chorioretinopathy (CSC) is a disease that causes fluid to collect under the retina. It affects the macula, which is in the center of the retina and is needed for sharp, clear vision. In many cases, CSC resolves on its own and does not need treatment. However, in some cases it does not go away or comes back after treatment. This is known as chronic CSC.

• Chronic CSC may be caused by hormones called androgens. Finasteride is a drug that can alter the effects certain of androgens. Researchers want to compare finasteride with a placebo to see if it is a safe and effective treatment for chronic CSC.

Objectives:

• To see if finasteride is a safe and effective treatment for chronic CSC.

Eligibility:

• Individuals at least 18 years of age who have chronic CSC in one or both eyes.

Design:

• Participants will be screened with a physical exam and medical history. A full eye exam will be performed. Blood and urine samples will also be collected.

• Some participants may have photodynamic therapy (PDT), the standard treatment for CSC. PDT helps to reduce the amount of fluid in the eye. Participants will need to wait for 3 months after PDT before starting the finasteride study.

• Participants will be separated into two groups. One group will take finasteride 5 mg (formulated into capsules); the other group will take a placebo capsule. All participants will take the capsules for 3 months.

• After 3 months on the assigned capsule (finasteride or placebo), all participants will have the opportunity to take finasteride for at least another 4 years and 9 months. This phase of the study is optional.

• Participants will have regular study visits. At each visit, they will have physical exams and eye exams. They will also provide blood and urine samples.

• During the first 3 months, participants will have 2 study visits. After 3 months, if the participant continues in the optional (or as needed) phase of the protocol, visits will occur at Month 6, Month 12 and every 12 months thereafter. However, additional visits may be needed.

Description:

Objective:

Central serous chorioretinopathy (CSC) is a chorioretinal disorder characterized by an accumulation of serous fluid under the retina. Although acute CSC tends to resolve spontaneously on its own with minimal sequelae, chronic CSC tends to persist and lead to irreversible visual loss. The pathogenesis of CSC is complex. However, systemic androgens have been implicated. Finasteride is an anti-androgen medication that is widely used in the treatment of various conditions. A previous study performed at the NEI demonstrated a reduction in the amount of subretinal fluid among participants treated with 5 mg of finasteride. The objective of this study is to further investigate the efficacy of oral finasteride as a treatment for chronic CSC.

Study Population:

Thirty-eight participants with chronic CSC are eligible. Up to an additional four participants may be enrolled to account for participants who withdraw from the study prior to Month 3.

Design:

In this Phase II, single-center, placebo-controlled, double-masked, randomized trial, investigational product will be administered to two different groups. Half of the participants will be randomized to 5 mg oral finasteride for the initial three months. The other half of the participants will be randomized to placebo for the first three months. At the end of three months of treatment, all participants may be followed for at least four years and nine months. During this follow-up period, all participants will be able to receive finasteride therapy pro re nata (PRN) if subretinal fluid re-emerges. The PRN phase will last until the last participant completes the five years of follow-up. Other standard care treatments, such as photodynamic therapy, will also be permitted after the primary outcome at three months.

Outcome Measures:

The primary outcome for regulatory filing is the proportion of participants with an improvement in best-corrected visual acuity (BCVA) ≥ 15 letters at three months compared to baseline in the study eye. The primary outcome for publication of the study results is the proportion of participants with a subretinal fluid volume decrease ≥ 50% at three months compared to baseline in the study eye. Secondary efficacy outcomes include changes in BCVA, changes in the maximum retinal volume as measured on optical coherence tomography (OCT), changes in central retinal thickness on OCT, changes in leakage as seen on fluorescein angiography (FA), changes in size of existing plaque(s) on indocyanine green (ICG) angiography, changes in autofluorescence patterns seen on fundus autofluorescence (FAF) imaging, changes in mean macular sensitivity as assessed by microperimetry, changes in serum levels of testosterone and dihydrotestosterone (DHT), as well as changes in urine levels of cortisol during the study period. Safety outcomes include the number and severity of adverse reactions from the investigational product and the number of withdrawals.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA:

• Participant must have chronic Central Serous Chorioretinopathy (CSC) in at least one eye as defined by all of the following criteria. This eye will be referred to as the study eye.

• The presence of subretinal fluid, as determined by optical coherence tomography (OCT), AND

• The subretinal fluid must have been present for at least three months or recurrent in cases of chronic CSC/diffuse retinal pigment epitheliopathy, AND/OR

• The presence of characteristic fluorescein angiographic or autofluorescence features of CSC, such as one or more pinpoint leaks and/or diffuse retinal pigment epitheliopathy noted on fluorescein or descending tract lesions on autofluorescence.

• Participant must have a steady fixation in the study eye.

• Participant must have media clear enough in the foveal or parafoveal area in the study eye for good quality photographs.

• Participant must have visual acuity between 20/25 and 20/400 in the study eye.

EXCLUSION CRITERIA:

• Participant has evidence of choroidal neovascularization (CNV) in the study eye.

• Participant is expected to need ocular surgery in the study eye during the first three months of the study.

• Participant has had photodynamic therapy (PDT) or focal laser treatment in the study eye within three months prior to enrollment or is expected to need PDT or focal laser treatment in the study eye during the first three months of the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Central Serous Chorioretinopathy
• Retinal Disease
• Retinal Diseases

Intervention

Drug:
• Finasteride
Finasteride is available as white, round 5 mg tablets. During the masked period, the tablets are re-formulated in capsules with inactive ingredients. The re-formulated finasteride capsules are indistinguishable from the placebo capsules.
• Placebo
Capsule with no active ingredients to mimic finasteride

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
National Eye Institute (NEI)	The EMMES Corporation

Country where clinical trial is conducted

United States, 

References & Publications (3)

Gomolin JE. Choroidal neovascularization and central serous chorioretinopathy. Can J Ophthalmol. 1989 Feb;24(1):20-3. — View Citation

Spahn C, Wiek J, Burger T, Hansen L. Psychosomatic aspects in patients with central serous chorioretinopathy. Br J Ophthalmol. 2003 Jun;87(6):704-8. — View Citation

Tewari HK, Gadia R, Kumar D, Venkatesh P, Garg SP. Sympathetic-parasympathetic activity and reactivity in central serous chorioretinopathy: a case-control study. Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3474-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants With an Improvement in Best-corrected Visual Acuity (BCVA) = 15 Letters at 3 Months Compared to Baseline.	This is the regulatory filing primary outcome measure. Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.	Month 3	No
Primary	Proportion of Participants With a Reduction in Subretinal Fluid Volume = 50% at 3 Months Compared to Baseline	This is the primary outcome measure for publication of study results. Subretinal fluid volume will be determined by manually moving the segmentation lines of the optical coherence tomography (OCT) image using the "Edit Segmentation" function of the Cirrus™ HD-OCT software. The segmentation lines will be edited to outline the inner and outer borders of the subretinal fluid pocket. This will be done manually for all the individual B-scans of each OCT image, after which the software algorithm automatically calculates the subretinal fluid volume.	Month 3	No
Secondary	Number of Participants With Adverse Reactions Related to the Investigational Product	The outcome measure refers only to events that were classified as related to the investigational product.	Duration of the study, up to 1.5 years	Yes
Secondary	Number of Participants Who Withdrew From the Study		Duration of the study, up to 1.5 years	Yes
Secondary	Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at Month 3 Compared to Baseline	Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.; A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome.	Month 3	No
Secondary	Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at the Safety Visit Compared to Baseline	Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.; A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome.	Final Study Visit	No
Secondary	Percent Change in Subretinal Fluid Volume in the Study Eye at Month 3 Compared to Baseline	Subretinal fluid volume will be determined by manually moving the segmentation lines of the optical coherence tomography (OCT) image using the "Edit Segmentation" function of the Cirrus™ HD-OCT software. The segmentation lines will be edited to outline the inner and outer borders of the subretinal fluid pocket. This will be done manually for all the individual B-scans of each OCT image, after which the software algorithm automatically calculates the subretinal fluid volume.	Month 3	No
Secondary	Changes in Mean Macular Sensitivity in the Study Eye at Month 3 Compared to Baseline	Microperimetry was used to assess macular sensitivity.	Month 3	No
Secondary	Changes in Mean Macular Sensitivity in the Study Eye at the Safety Visit Compared to Baseline	Microperimetry was used to assess macular sensitivity.	Final Study Visit	No
Secondary	Change in Central Retinal Thickness in the Study Eye at Month 3 Compared to Baseline	Central retinal thickness was assessed by spectral-domain optical coherence tomography (SD-OCT).	Month 3	No
Secondary	Change in Central Retinal Thickness in the Study Eye at the Safety Visit Compared to Baseline	Central retinal thickness was assessed by spectral-domain optical coherence tomography (SD-OCT).	Final Study Visit	No
Secondary	Change in Serum Dihydrotestosterone (DHT) Concentration at Month 3 Compared to Baseline	The mean change is reported in picograms of DHT per milliliter of serum.	Month 3	No
Secondary	Change in Serum Dihydrotestosterone (DHT) Concentration at the Safety Visit Compared to Baseline	The mean change is reported in picograms of DHT per milliliter of serum.	Final Study Visit	No
Secondary	Change in Serum Testosterone Concentration at Month 3 Compared to Baseline	The mean change is reported in nanograms of testosterone per decaliter of serum.	Month 3	No
Secondary	Change in Serum Testosterone Concentration at the Safety Visit Compared to Baseline	The mean change is reported in nanograms of testosterone per decaliter of serum.	Final Study Visit	No
Secondary	Change in Urinary Levels of Cortisol at Month 3 Compared to Baseline	The mean change is reported in micrograms (µg).	Month 3	No
Secondary	Change in Urinary Levels of Cortisol at the Safety Visit Compared to Baseline	The mean change is reported in micrograms (µg).	Final Study Visit	No
Secondary	Number of Participants Presenting No Change in Autofluorescence Patterns at Month 3 Compared to Baseline	Autofluorescence patterns as observed on Fundus Autofluorescence (FAF) imaging	Month 3	No
Secondary	Number of Participants Presenting No Change in Autofluorescence Patterns at the Safety Visit Compared to Baseline	Autofluorescence patterns as observed on Fundus Autofluorescence (FAF) imaging	Final Study Visit	No
Secondary	Number of Participants Presenting No Change in Size of Existing Plaque(s) on Indocyanine Green (ICG) Angiography at Month 3 Compared to Baseline		Month 3	No
Secondary	Number of Participants Presenting No Change in Size of Existing Plaque(s) on Indocyanine Green (ICG) Angiography at the Safety Visit Compared to Baseline		Final Study Visit	No
Secondary	Number of Participants Presenting No Change in Fluid Leakage at Month 3 Compared to Baseline	Changes in leakage as observed on fluorescein angiography (FA)	Month 3	No
Secondary	Number of Participants Presenting No Change in Fluid Leakage at the Safety Visit Compared to Baseline	Changes in leakage as observed on fluorescein angiography (FA)	Final Study Visit	No