Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Conditions
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Retinitis Pigmentosa, Retinal Diseases, Eye Diseases, Eye Disease, Hereditary, Retinal Degeneration

Intervention / Treatment
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* Drug: Valproic Acid


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Valproic acid<br> | Drug: Valproic Acid<br>* One 500mg tablet by mouth daily<br>* Other names: Valproate;|
| No Intervention: Control<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in visual field area from baseline to 48 weeks | Visual field area will be measured using kinetic perimetry (Goldmann perimetry) or static perimetry including the central 30 field. | Baseline, week 24, and week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in best corrected visual acuity (BCVA) | BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) | Baseline, week 24, and week 48 | 
| Mean change in 30-Hz flicker Electroretinogram (ERG) amplitude |  | Baseline and week 48 | 
| Mean change in central macular thickness | Central macular thickness as measured by Optical Coherence Tomography (OCT) | Baseline, week 24, and week 48 | 
| Mean change in fundus appearance | Fundus appearance as judged by color fundus photography | Baseline and week 48 | 
| Mean change in total score on vision-related quality of life | Total score on vision-related quality of life as measured by the National Eye Institute Visual Function Questionnaire (NEI-VFQ25) | Baseline and week 48 | 
| Occurrence of adverse effect related to Valproic acid |  | Baseline through 48 weeks | 
| Changes in clinical laboratory data | 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) | Baseline through 48 weeks | 
| Mean change in central macular volume | Central macular volume as measured by Optical Coherence Tomography (OCT) | Baseline, week 24, and week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Retinitis pigmentosa, Valproic acid