Pilot Study for the Evaluation of Finasteride in the Treatment of Chronic Central Serous Chorioretinopathy

• Sponsor: National Eye Institute (NEI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00837252
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 13.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Central serous chorioretinopathy (CSC) is a retinal disorder characterized by an accumulation of serous fluid under the retina. Although acute CSC tends to spontaneously resolve 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. The objective of this study was to investigate the safety and potential efficacy of oral finasteride as a treatment for chronic CSC.

Five participants with chronic CSC were enrolled into this uncontrolled, unmasked, Phase I/II study. An oral dose of finasteride, 5 mg daily, was administered to all participants for three months.

Following this, finasteride was withheld and participants were observed for another three months. If a participant experienced a beneficial effect during the period in which he received finasteride and then experienced a relapse during the observation period, finasteride was re-instituted for the remaining period of the study. Relapse was defined as a return to the baseline maximum lesion height and/or return to baseline lesion volume.

Condition or Disease	Intervention/Treatment	Phase
Retinal Disease	Drug: Finasteride	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study for the Evaluation of Finasteride in the Treatment of Chronic Central Serous Chorioretinopathy
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Finasteride	Drug: Finasteride; Participants received 5mg of oral finasteride daily for three months.; Other Names: Propecia Proscar

Outcome Measures

Primary Outcome Measures

1. Change in Visual Acuity at Month 3 Compared to Baseline. [3 months]

   Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This 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 Snellen measurement is 20/20.

Secondary Outcome Measures

1. Change in Visual Acuity at Month 6 Compared to Baseline [6 months]

   Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This 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 Snellen measurement is 20/20.

2. Change in Center-Subfield Macular Thickness at Month 3 Compared to Baseline [3 months]

   Central-subfield macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

3. Change in Center-Subfield Macular Thickness at Month 6 Compared to Baseline [6 months]

   Central-subfield macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

4. Change in Subretinal Fluid Volume at Month 3 Compared to Baseline [3 Months]

   Subretinal fluid volume was calculated after manually outlining the inner and outer borders of the subretinal fluid packet in the optical coherence tomography (OCT) images using the "Edit Segmentation" function of the Cirrus HD-OCT software. In cases where a pigment epithelial detachment was present, the volume of the pigment epithelial detachment was included in the calculation of subretinal fluid volume.

5. Change in Subretinal Fluid Volume at Month 6 Compared to Baseline [6 Months]

   Subretinal fluid volume was calculated after manually outlining the inner and outer borders of the subretinal fluid packet in the optical coherence tomography (OCT) images using the "Edit Segmentation" function of the Cirrus HD-OCT software. In cases where a pigment epithelial detachment was present, the volume of the pigment epithelial detachment was included in the calculation of subretinal fluid volume.

6. Change in Serum Dihydrotestosterone (DHT) Concentration at Month 3 Compared to Baseline [3 Months]

   The concentration of dihydrotestosterone (DHT) in blood serum was assessed from each participant at baseline and at Month 3. The mean change from baseline to Month 3 is reported here in picograms of DHT per milliliter of serum.

7. Change in Serum Dihydrotestosterone (DHT) Concentration at Month 6 Compared to Baseline [6 Months]

   The concentration of dihydrotestosterone (DHT) in blood serum was assessed from each participant at baseline and at Month 6. The mean change from baseline to Month 6 is reported here in picograms of DHT per milliliter of serum.

8. Change in Serum Testosterone Level at Month 3 Compared to Baseline [3 Months]

   The concentration of testosterone in blood serum was assessed from each participant at baseline and at Month 3. The mean change from baseline to Month 3 is reported here in nanograms of testosterone per decaliter of serum.

9. Change in Serum Testosterone Level at Month 6 Compared to Baseline [6 Months]

   The concentration of testosterone in blood serum was assessed from each participant at baseline and at Month 6. The mean change from baseline to Month 6 is reported here in nanograms of testosterone per decaliter of serum.

10. Change in Urinary Cortisol Level at Month 3 Compared to Baseline [3 Months]

    The amount of cortisol found in urine was assessed from each participant at baseline and at Month 3. The mean change from baseline to Month 3 is reported here in micrograms.

11. Change in Urinary Cortisol Level at Month 6 Compared to Baseline [6 Months]

    The amount of cortisol found in urine was assessed from each participant at baseline and at Month 6. The mean change from baseline to Month 6 is reported here in micrograms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Participant-Level Inclusion Criteria

1. Participant must be 18 years of age or older.

2. Participant must understand and sign the protocol's informed consent document.

3. Female participants of childbearing potential must not be pregnant or breast-feeding, must have a negative pregnancy test at screening and must be willing to undergo monthly pregnancy tests throughout the study.

4. Female participants of childbearing potential must agree to practice two* acceptable methods of birth control throughout the course of the study and for three months after their last oral dose of finasteride. Acceptable methods of birth control include hormonal contraception (birth control pills, injected hormones or vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom and spermicide) or surgical sterilization (hysterectomy, tubal ligation or vasectomy in a partner).

*Participants with hysterectomy or vasectomy are exempt from using two methods of birth control. However female participants with a tubal ligation are not exempt and are required to practice another acceptable method of birth control.

1. Participant agrees to take the appropriate precautions to ensure that persons who are pregnant, nursing or of childbearing potential do not handle the finasteride tablets.

Participant-Level Exclusion Criteria

1. Participant is in another investigational study and actively receiving study therapy.

2. Participant is unable to comply with study procedures or follow-up visits.

3. Participant has evidence of ocular disease other than CSC in either eye that may confound the outcome of the study (e.g., diabetic retinopathy with 10 or more hemorrhages or microaneurysms, uveitis, pseudovitelliform macular degeneration, moderate/severe myopia, etc.).

4. Participant has evidence of CNV.

5. Participant has abnormal liver function testing as defined by elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels that are greater than twice the respective upper limits of normal (ULN), i.e., ALT > 82 U/L and/or AST

68 U/L. If a participant has ALT or AST levels greater than twice the ULN, the participant can be enrolled if cleared by hepatology.

1. Participant is expected to need ocular surgery during the course of the trial.

2. Participant is on steroid medication (oral, topical or inhaled).

3. Participant is on ocular or systemic medications known to be toxic to the lens, retina or optic nerve.

4. Participant has a systemic condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control).

Study Eye Inclusion Criteria

1. Eligible participants must have chronic CSC in at least one eye as defined by all of the following criteria:

2. The presence of subretinal fluid, as determined by spectral domain OCT, AND

3. The subretinal fluid must have been present for at least three months, or there is a recurrence of subretinal fluid within the past three months, AND

4. The presence of characteristic fluorescein angiographic or autofluorescence features of CSC, such as one or more pinpoint leaks and/or diffuse retinal pigment epitheliopathy. This eye will be referred to as the "study eye."

5. Participant must have a steady fixation in the study eye in the foveal or parafoveal area and media clear enough for good quality photographs.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Eye Institute (NEI)

Investigators

• Principal Investigator: Catherine B Meyerle, MD, National Eye Institute (NEI)

Study Documents (Full-Text)

None provided.

More Information

Publications

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

• Responsible Party: National Eye Institute (NEI)
• ClinicalTrials.gov Identifier: NCT00837252
• Other Study ID Numbers: 090075; 09-EI-0075
• First Posted: Feb 5, 2009
• Last Update Posted: Sep 26, 2016
• Last Verified: Sep 1, 2016

• Keywords provided by National Eye Institute (NEI): Central Serous Chorioretinopathy; Finasteride; Proscar; Retinal Eye Disease
• Additional relevant MeSH terms: Retinal Diseases; Central Serous Chorioretinopathy; Finasteride

Study Results

Participant Flow

Arm/Group Title	Finasteride
Arm/Group Description	All five study participants (all of whom were diagnosed with chronic CSC) were administered a 5mg oral dose of finasteride daily for three months. After three months, the finasteride was withheld and the participants were observed for another three months.
Period Title: Overall Study
STARTED	5
COMPLETED	5
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Finasteride
Arm/Group Description
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (10.4)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	5 100%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Change in Visual Acuity at Month 3 Compared to Baseline.
Description	Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This 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 Snellen measurement is 20/20.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	5
Mean (Standard Deviation) [ETDRS letters]	0 (22)

2. Secondary Outcome

Title	Change in Visual Acuity at Month 6 Compared to Baseline
Description	Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This 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 Snellen measurement is 20/20.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	5
Mean (Standard Deviation) [ETDRS letters]	-3 (23)

3. Secondary Outcome

Title	Change in Center-Subfield Macular Thickness at Month 3 Compared to Baseline
Description	Central-subfield macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	5
Mean (Standard Deviation) [µm]	-86 (105)

4. Secondary Outcome

Title	Change in Center-Subfield Macular Thickness at Month 6 Compared to Baseline
Description	Central-subfield macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	5
Mean (Standard Deviation) [µm]	-69 (103)

5. Secondary Outcome

Title	Change in Subretinal Fluid Volume at Month 3 Compared to Baseline
Description	Subretinal fluid volume was calculated after manually outlining the inner and outer borders of the subretinal fluid packet in the optical coherence tomography (OCT) images using the "Edit Segmentation" function of the Cirrus HD-OCT software. In cases where a pigment epithelial detachment was present, the volume of the pigment epithelial detachment was included in the calculation of subretinal fluid volume.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	5
Mean (Standard Deviation) [µL]	-0.58 (0.71)

6. Secondary Outcome

Title	Change in Subretinal Fluid Volume at Month 6 Compared to Baseline
Description	Subretinal fluid volume was calculated after manually outlining the inner and outer borders of the subretinal fluid packet in the optical coherence tomography (OCT) images using the "Edit Segmentation" function of the Cirrus HD-OCT software. In cases where a pigment epithelial detachment was present, the volume of the pigment epithelial detachment was included in the calculation of subretinal fluid volume.
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	5
Mean (Standard Deviation) [µL]	-0.53 (0.72)

7. Secondary Outcome

Title	Change in Serum Dihydrotestosterone (DHT) Concentration at Month 3 Compared to Baseline
Description	The concentration of dihydrotestosterone (DHT) in blood serum was assessed from each participant at baseline and at Month 3. The mean change from baseline to Month 3 is reported here in picograms of DHT per milliliter of serum.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	5
Mean (Standard Deviation) [pg/mL]	-246 (116)

8. Secondary Outcome

Title	Change in Serum Dihydrotestosterone (DHT) Concentration at Month 6 Compared to Baseline
Description	The concentration of dihydrotestosterone (DHT) in blood serum was assessed from each participant at baseline and at Month 6. The mean change from baseline to Month 6 is reported here in picograms of DHT per milliliter of serum.
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

Only the 3 patients who were rechallenged with finasteride after Month 3 were included in this analysis.

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	3
Mean (Standard Deviation) [pg/mL]	-296 (87)

9. Secondary Outcome

Title	Change in Serum Testosterone Level at Month 3 Compared to Baseline
Description	The concentration of testosterone in blood serum was assessed from each participant at baseline and at Month 3. The mean change from baseline to Month 3 is reported here in nanograms of testosterone per decaliter of serum.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	5
Mean (Standard Deviation) [ng/dL]	0.38 (3.63)

10. Secondary Outcome

Title	Change in Serum Testosterone Level at Month 6 Compared to Baseline
Description	The concentration of testosterone in blood serum was assessed from each participant at baseline and at Month 6. The mean change from baseline to Month 6 is reported here in nanograms of testosterone per decaliter of serum.
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	5
Mean (Standard Deviation) [ng/dL]	-0.4 (3.38)

11. Secondary Outcome

Title	Change in Urinary Cortisol Level at Month 3 Compared to Baseline
Description	The amount of cortisol found in urine was assessed from each participant at baseline and at Month 3. The mean change from baseline to Month 3 is reported here in micrograms.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	5
Mean (Standard Deviation) [µg]	3 (24)

12. Secondary Outcome

Title	Change in Urinary Cortisol Level at Month 6 Compared to Baseline
Description	The amount of cortisol found in urine was assessed from each participant at baseline and at Month 6. The mean change from baseline to Month 6 is reported here in micrograms.
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Finasteride
Arm/Group Description
Measure Participants	5
Mean (Standard Deviation) [µg]	-2 (18)

Adverse Events

Time Frame	1 year
Arm/Group Title	Finasteride
Arm/Group Description
All Cause Mortality
	Finasteride
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Finasteride
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Finasteride
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Leukopenia	1/5 (20%)	1
Gastrointestinal disorders
Dyspepsia	1/5 (20%)	1
Constipation	1/5 (20%)	1
Nausea	1/5 (20%)	1
General disorders
Influenza like illness	1/5 (20%)	1
Infections and infestations
Viral infection	1/5 (20%)	1
Upper respiratory tract infection	1/5 (20%)	1
Investigations
Alanine aminotransferase increased	1/5 (20%)	1
Heart rate increased	1/5 (20%)	1
Blood pressure increased	2/5 (40%)	2
White blood cell count decreased	1/5 (20%)	1
Aspartate aminotransferase decreased	1/5 (20%)	1
Metabolism and nutrition disorders
Decreased appetite	1/5 (20%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	1/5 (20%)	1
Psychiatric disorders
Libido decreased	2/5 (40%)	2
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	1/5 (20%)	1
Vascular disorders
Hypotension	1/5 (20%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.