Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa

Phase 2

Completed

• Conditions: Retinitis Pigmentosa; Retinal Diseases; Eye Disease, Hereditary; Retinal Degeneration; Eye Diseases
• Interventions: Drug: Valproic Acid

• Registration Number: NCT01399515
• Lead Sponsor: Seoul National University Hospital

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.

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 Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-05-03
• Study First Submitted QC: 2011-07-20
• Study First Posted: 2011-07-21
• Primary Completion: 2013-08
• Study Completion: 2015-11
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-12
• Last Update Posted: 2016-04-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Valproic acid	Valproic Acid	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Occurrence of adverse effect related to Valproic acid	Baseline through 48 weeks
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 best corrected visual acuity (BCVA)	Baseline, week 24, and week 48	BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
Mean change in fundus appearance	Baseline and week 48	Fundus appearance as judged by color fundus photography
Mean change in 30-Hz flicker Electroretinogram (ERG) amplitude	Baseline and week 48
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)
Mean change in central macular volume	Baseline, week 24, and week 48	Central macular volume as measured by Optical Coherence Tomography (OCT)
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)

Trial Locations

Locations (1)

Department of Ophthalmology, Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of