Trial of Oral Valproic Acid for Retinitis Pigmentosa
Condition: Retinitis Pigmentosa
MeSH terms: Retinitis; Retinitis Pigmentosa
Intervention: Valproic Acid; Placebo
Intervention description: One to four 250mg softgels by mouth daily (dose determined by body weight); Dosage per subject weight- same schedule as the active comparator
Intervention MeSH terms: Valproic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: retinitis pigmentosa; valproic acid; visual field

Summary:

      The objectives of this study are to evaluate the efficacy of Valproic Acid (VPA) to both slow
      the progression of visual function loss and/or to restore visual function in patients with
      Autosomal Dominant Retinitis Pigmentosa (RP) and to collect safety and tolerability
      information.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Understand/sign the IRB-approved study informed consent document.

          2. Age greater than or equal to 18 years, no upper age limit

          3. Males and non-child bearing females must weigh ≥40 Kg and ≤158.9 Kg; Females of child
             bearing potential must weigh ≥40 Kg and ≤74.9 Kg.

          4. Diagnosis of Retinitis Pigmentosa (RP).

          5. Visual acuity of greater than or equal to 35 letters in at least one eye as measured
             by the EVA-ETDRS (equivalent to 20/200 on a Snellen chart).

          6. Genotyped as autosomal dominant form of RP.

          7. Female subjects of childbearing potential and male subjects able to father children
             must have (or have a partner who has) had a hysterectomy or vasectomy, be completely
             abstinent from intercourse or must commit to practice at least two acceptable methods
             of contraception to minimize the chance of pregnancy during the study and for the 13
             week period after stopping the study drug.

          8. Female subjects of childbearing potential must have a negative urine pregnancy test at
             study entry and throughout the duration of the study.

          9. Willingness to comply with the protocol.

        Exclusion Criteria:

          1. Medical problems that make consistent follow-up over the treatment period unlikely
             (e.g. stroke, severe MI, end stage malignancy), or in general a poor medical risk
             because of other systemic diseases or active uncontrolled infections.

          2. Other retinal diseases: Glaucoma, retinal inflammatory disease (CME is allowable),
             cataract worse than +2 NS, or herpes simplex virus of the eye.

          3. Intact visual field of 5⁰ or less.

          4. Subject unable to provide reliable perimetry measurements in both eyes for both static
             and kinetic visual field, as determined by the Reading Center.

          5. Diabetes.

          6. History of cancer (other than non-melanoma skin cancer) diagnosed, or requiring
             treatment within the past 2 years.

          7. A hemoglobin concentration, a platelet count or an absolute neutrophil count below the
             lower limit of normal at study entry.

          8. Suspected liver dysfunction determined by having liver function values elevated above
             the upper limit of normal.

          9. History of pancreatitis by clinical features and/or laboratory abnormalities in the
             last 12 months.

         10. Renal dysfunction based on serum creatinine,(MDRD) equation.

         11. Urea cycle disorders.

         12. History of neurological conditions including epilepsy, history of brain injury,
             encephalitis, or any organic brain syndrome.

         13. History of schizophrenia, schizoaffective disorder, bipolar disorder, suicidality or
             organic mental disorders.

         14. Currently receiving valproic acid or other anti-convulsants.

         15. Sensitive to or have ever had an allergic reaction to valproic Acid.

         16. Sensitive to or have ever had an allergic reaction to peanuts as peanut oil is an
             inactive ingredient in valproic acid capsules and the placebo.

         17. Has taken one of the disallowed drugs at least 2 weeks prior to randomization.

         18. Pregnant women.

         19. Lactating mothers who are breast feeding their babies.

         20. RP patients involved in other clinical trials within the last 3 months.

         21. Require enrollment by consent of a legally authorized representative.

         22. Persons who are unable to read are not allowed to consent for themselves or others to
             participate in this study.

         23. The potential participant lives in the same household as a current participant in this
             protocol.