A Phase II Multiple Site, Randomized, Placebo-Controlled Trial of Oral Valproic Acid for Retinitis Pigmentosa Protocol #H-13371

Overview

Status: Enrolling by invitation
Keywords: Retinitis pigmentosa , ophthalmology , retina
IRB Number: 00044782
Specialty: Ophthalmology, Ophthalmology
Sub Specialties: Retinal Diseases,

Brief Summary

 

 
The purpose of this study is to evaluate the efficacy of VPA (valproic acid) to both slow the progression of visual function loss and/or to restore visual function in patients with RP, and to collect safety and tolerability information in this patient population.

Principal Investigator: Paul Bernstein
Department: Ophthalmology-Services
Co Investigator: Judith Warner
Co Investigator: Briana Sawyer
Co Investigator: Kimberley Wegner
Co Investigator: Susan Allman
Co Investigator: Mary Elizabeth Hartnett
Co Investigator: Mike Teske

Contact Information

Name:Kimberley Wegner
Phone: 801-581-6265
Email: kimberley.wegner@hsc.utah.edu

Inclusion Criteria

1. Understand and sign the IRB-approved informed consent document for the study.
 
2. Age: at least 18 years.
 
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) including photoreceptor degeneration established by visual field constriction, night blindness, marked reduction of ERG responses, and the clinical signs of RP including waxy pallor of the optic nerve, vascular attenuation and/or the presence of intraretinal pigment on clinical examination.
 
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. Acceptable methods of contraception include hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods (diaphragm, condom) with spermicide, or surgical sterilization (tubal ligation).
 
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.
 
* THE FOLLOWING DEFINITION WILL BE USED TO DETERMINE CHILDBEARING POTENTIAL: A FEMALE SUBJECT WHO IS CONSIDERED NON-CHILDBEARING DUE TO A MEDICAL CONDITION (I.E., SUBJECT HAS PREVIOUSLY UNDERGONE A HYSTERECTOMY) DOES NOT NEED A PREGNANCY TEST OR CONTRACEPTION. WOMEN OVER AGE 55 WHO HAVE NOT HAD A PERIOD FOR ONE YEAR WILL BE CONSIDERED MENOPAUSAL AND DO NOT NEED A PREGNANCY TEST OR CONTRACEPTION.
 
WOMEN UNDER 55 MUST UNDERGO PREGNANCY TESTING AND USE CONTRACEPTION AS OUTLINED IN 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, (Note: CME is allowable), cataract worse than +2 NS or herpes simplex virus of the eye.
 
3. Intact visual field of 5° or less with measurable kinetic field on the V4e, III4e, or I4e isopters.
 
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 last 2 years.
 
7. A hemoglobin concentration, a platelet count or an absolute neutrophil count below the lower limit of normal at study entry. The limits of normal are defined by each site and are agreed to by the medical monitor
 
8. Suspected liver dysfunction determined by having alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin 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 using the Modification of Diet in Renal Disease (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, suicidal 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 following drugs at least 2 weeks prior to randomization as these drugs are specifically known to interact with valproic acid: aspirin (except that prophylactic use of ‘low-dose’ aspirin (less than or equal to 81 mg) is allowed),, felbamate, rifampin, amitriptyline/nortriptyline, carbamazepine, clonazepam, diazepam, ethosuximide, lamotrigine, phenobarbital, primidone, phenytoin, tolbutamide, warfarin, or zidovudine.
 
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. A potential participant cannot participate if he/she lives in the same household as a current participant in this protocol