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Trial of Oral Valproic Acid for Retinitis Pigmentosa

Information source: Foundation Fighting Blindness Clinical Research Institute
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Retinitis Pigmentosa

Intervention: Valproic Acid (Drug); Placebo (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Foundation Fighting Blindness Clinical Research Institute

Official(s) and/or principal investigator(s):
Judith Chiostri, MS, Study Director, Affiliation: Foundation Fighting Blindness Clinical Research Institute

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.

Clinical Details

Official title: A Phase II Multiple Site, Randomized, Placebo-Controlled Trial of Oral Valproic Acid for Autosomal Dominant Retinitis Pigmentosa

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Mean change in visual field area from baseline to 52 weeks.

Secondary outcome:

Static perimetry measurements in the full visual field

Mean change in best corrected visual acuity.

Color contrast sensitivity

Mean change in peak Electroretinogram (ERG) amplitude

Mean change in central macular thickness and macular volume

Change in fundus appearance

Mean change in total score on vision-related quality of life.

Changes in clinical laboratory data

Changes in physical examination findings

Detailed description: Retinitis Pigmentosa (RP) is an incurable and untreatable group of heterogeneous retinal degenerative diseases that cause severe visual loss. There is currently no therapeutic that substantially slows the progression of this disease, and certainly none that can restore vision in RP patients. The Valproic Acid (VPA) study is designed as a six-site, interventional, prospective, randomized, placebo controlled, double-blinded study of 90 participants to evaluate the efficacy of oral Valproic Acid to both slow the progression of visual function loss and/or to restore visual function in patients with an Autosomal Dominant RP genetic mutation and to collect safety and tolerability information. Patients that participate in the study will be randomized to either placebo or VPA in a 1: 1 ratio.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Locations and Contacts

University of Miami, Bascom Palmer Eye Institute, Miami, Florida 33136, United States

University of Michigan, Ann Arbor, Ann Arbor, Michigan 48105, United States

Oregon Health & Science University, Portland, Oregon 97239, United States

University of Tennessee, Hamilton Eye Institute, Memphis, Tennessee 38163, United States

Retina Foundation of the Southwest, Dallas, Texas 75231, United States

University of Utah School of Medicine, Moran Eye Center, Salt Lake City, Utah 84132, United States

Additional Information

Click here for more information about this study: Clinical Trial page of the Foundation Fighting Blindness Website.

Related publications:

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Nowomiejska K, Vonthein R, Paetzold J, Zagorski Z, Kardon R, Schiefer U. Reaction time during semi-automated kinetic perimetry (SKP) in patients with advanced visual field loss. Acta Ophthalmol. 2010 Feb;88(1):65-9. doi: 10.1111/j.1755-3768.2008.01407.x. Epub 2009 Dec 16.

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Starting date: November 2010
Last updated: September 12, 2014

Page last updated: August 20, 2015

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