VPA_RP: Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa

Sponsor

Seoul National University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01399515

Collaborator

(none)

200

Enrollment

Location

Arms

Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of oral valproic acid to slow the progression of visual function and/or to improve the visual function in patients with retinitis pigmentosa (RP).

Enrolled subjects in valproic acid group will be treated with oral valproic acid 500mg daily for 48 weeks. Visual function and safety will be assess before and after treatment (48 weeks) between valproic acid and control groups.

Condition or Disease	Intervention/Treatment	Phase
Retinitis Pigmentosa Retinal Diseases Eye Diseases Eye Disease, Hereditary Retinal Degeneration	Drug: Valproic Acid	Phase 2

Detailed Description

This study is designed as a single-site, interventional, prospective, non-randomized, controlled study of 200 participants. Patients that participate in the study will be assigned to either valproic acid group or control in a 3:1 ratio.

Study Design

Study Type:

Interventional

Actual Enrollment :

200 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Study Start Date :

Mar 1, 2011

Actual Primary Completion Date :

Aug 1, 2013

Actual Study Completion Date :

Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Valproic acid	Drug: Valproic Acid One 500mg tablet by mouth daily Other Names: Valproate
No Intervention: Control

Arm

Intervention/Treatment

Active Comparator: Valproic acid

Drug: Valproic Acid

One 500mg tablet by mouth daily

Other Names:

Valproate

No Intervention: Control

Outcome Measures

Primary Outcome Measures

Mean change in visual field area from baseline to 48 weeks [Baseline, week 24, and week 48]
Visual field area will be measured using kinetic perimetry (Goldmann perimetry) or static perimetry including the central 30 field.

Secondary Outcome Measures

Mean change in best corrected visual acuity (BCVA) [Baseline, week 24, and week 48]
BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
Mean change in 30-Hz flicker Electroretinogram (ERG) amplitude [Baseline and week 48]
Mean change in central macular thickness [Baseline, week 24, and week 48]
Central macular thickness as measured by Optical Coherence Tomography (OCT)
Mean change in fundus appearance [Baseline and week 48]
Fundus appearance as judged by color fundus photography
Mean change in total score on vision-related quality of life [Baseline and week 48]
Total score on vision-related quality of life as measured by the National Eye Institute Visual Function Questionnaire (NEI-VFQ25)
Occurrence of adverse effect related to Valproic acid [Baseline through 48 weeks]
Changes in clinical laboratory data [Baseline through 48 weeks]
CBC, BUN, Creatinine, Liver panel (Cholesterol, Total protein, Albumin, Total bilirubin, Alkaline phosphatase, AST, ALT, GGT), Coagulation panel (PT INR, PT%, PT sec, aPTT, Fibrinogen), Electrolyte panel (Na, K, Cl, TCO2)
Mean change in central macular volume [Baseline, week 24, and week 48]
Central macular volume as measured by Optical Coherence Tomography (OCT)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of retinitis pigmentosa (RP) established by night blindness, visual field constriction, marked reduction of electroretinogram, and the clinical signs of RP in fundus examination
Best corrected visual acuity of 20/200 or more on a Snellen chart in at least one eye
Intact visual field of 5 or more as measured by the kinetic perimetry
Understand and sign the IRB-approved informed consent document for the study
Body weight: male (40 kg to 100 kg), female (40 kg to 80 kg)
Must be able to swallow tablets
Female subjects of childbearing potential must commit to practice acceptable methods of contraception

Exclusion Criteria:

Pregnant women
Lactating mothers
Medical problems that make consistent follow-up over the treatment period unlikely (e.g., stroke, myocardiac infarction, malignancy) or severe systemic disease
Other ocular disease: retinal disease other than RP or cystoid macular edema, glaucoma, cataract worse than +2PSC or infectious corneal disease
Coagulation disorder or bleeding-tendency
Liver dysfunction
Renal dysfunction
History of pancreatitis
History of neurological disorders including epilepsy, history of brain injury or any organic brain disorders
History of mental disorders including schizophrenia, bipolar disorder, or suicidality
Currently receiving valproic acid or other anti-convulsants
Has taken one of the following drugs at least 4 weeks prior to enrollment as these drugs are specifically known to affect the progression of RP: vitamin A, lutein, omega-3 fatty acid, or any antioxidant which affect the blood flow of retina or retinal function.