Trial of Oral Valproic Acid for Retinitis Pigmentosa (VPA)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Retinitis Pigmentosa |
Drug: Valproic Acid Drug: Placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Phase II Multiple Site, Randomized, Placebo-Controlled Trial of Oral Valproic Acid for Autosomal Dominant Retinitis Pigmentosa |
- Mean change in visual field area from baseline to 52 weeks. [ Time Frame: Screening, baseline, week 26, and week 52 ] [ Designated as safety issue: No ]Mean change in visual field area from baseline to 52 weeks. Visual field area will be measured using semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haig-Strait).
- Static perimetry measurements in the full visual field [ Time Frame: Screening, baseline, week 26, and week 52 ] [ Designated as safety issue: No ]Static perimetry measurements in the full visual field, including the central 30 field.
- Mean change in best corrected visual acuity. [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]Mean change in best corrected visual acuity as measured by Electronic Visual Acuity-Early Treatment Diabetic Retinopathy Study (EVA-ETDRS) visual acuity test.
- Color contrast sensitivity [ Time Frame: Baseline to 52 weeks ] [ Designated as safety issue: No ]Color contrast sensitivity as measured by ChromaTest.
- Mean change in peak Electroretinogram (ERG) amplitude [ Time Frame: Baseline to 52 weeks ] [ Designated as safety issue: No ]Mean change in peak Electroretinogram (ERG) amplitude
- Mean change in central macular thickness and macular volume [ Time Frame: Baseline to 52 weeks ] [ Designated as safety issue: No ]Mean change in central mauclar thickness and mean change in macular volume as measured by Optical Coherence Tomography (OCT).
- Change in fundus appearance [ Time Frame: Baseline to 52 weeks ] [ Designated as safety issue: No ]Change in fundus appearance as judged by color retinal photography.
- Mean change in total score on vision-related quality of life. [ Time Frame: Baseline to 52 weeks ] [ Designated as safety issue: No ]Mean change in total score on vision-related quality of life as measured by the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ25).
- Changes in clinical laboratory data [ Time Frame: Baseline through 15 months ] [ Designated as safety issue: Yes ]Changes in clinical laboratory data
- Changes in physical examination findings [ Time Frame: Baseline through 15 months ] [ Designated as safety issue: Yes ]Changes in physical examination findings.
| Estimated Enrollment: | 90 |
| Study Start Date: | November 2010 |
| Estimated Study Completion Date: | September 2014 |
| Estimated Primary Completion Date: | March 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Valproic Acid
Subjects who receive valproic acid
|
Drug: Valproic Acid
One to four 250mg softgels by mouth daily (dose determined by body weight)
Other Name: Valproate
|
|
Placebo Comparator: Placebo
Subjects who receive placebo
|
Drug: Placebo
Dosage per subject weight- same schedule as the active comparator
|
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| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Understand/sign the IRB-approved study informed consent document.
- Age greater than or equal to 18 years, no upper age limit
- 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.
- Diagnosis of Retinitis Pigmentosa (RP).
- 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).
- Genotyped as autosomal dominant form of RP.
- 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.
- Female subjects of childbearing potential must have a negative urine pregnancy test at study entry and throughout the duration of the study.
- Willingness to comply with the protocol.
Exclusion Criteria:
- 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.
- Other retinal diseases: Glaucoma, retinal inflammatory disease (CME is allowable), cataract worse than +2 NS, or herpes simplex virus of the eye.
- Intact visual field of 5⁰ or less.
- Subject unable to provide reliable perimetry measurements in both eyes for both static and kinetic visual field, as determined by the Reading Center.
- Diabetes.
- History of cancer (other than non-melanoma skin cancer) diagnosed, or requiring treatment within the past 2 years.
- A hemoglobin concentration, a platelet count or an absolute neutrophil count below the lower limit of normal at study entry.
- Suspected liver dysfunction determined by having liver function values elevated above the upper limit of normal.
- History of pancreatitis by clinical features and/or laboratory abnormalities in the last 12 months.
- Renal dysfunction based on serum creatinine,(MDRD) equation.
- Urea cycle disorders.
- History of neurological conditions including epilepsy, history of brain injury, encephalitis, or any organic brain syndrome.
- History of schizophrenia, schizoaffective disorder, bipolar disorder, suicidality or organic mental disorders.
- Currently receiving valproic acid or other anti-convulsants.
- Sensitive to or have ever had an allergic reaction to valproic Acid.
- 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.
- Has taken one of the disallowed drugs at least 2 weeks prior to randomization.
- Pregnant women.
- Lactating mothers who are breast feeding their babies.
- RP patients involved in other clinical trials within the last 3 months.
- Require enrollment by consent of a legally authorized representative.
- Persons who are unable to read are not allowed to consent for themselves or others to participate in this study.
- The potential participant lives in the same household as a current participant in this protocol.
Contacts and Locations| United States, Florida | |
| University of Miami, Bascom Palmer Eye Institute | Recruiting |
| Miami, Florida, United States, 33136 | |
| Contact: Potyra Aroucha 305-202-4731 PAroucha@med.miami.edu | |
| Principal Investigator: Byron Lam, MD | |
| United States, Michigan | |
| University of Michigan, Ann Arbor | Recruiting |
| Ann Arbor, Michigan, United States, 48105 | |
| Contact: Pamela Titus, COT 734-936-0318 pamtitus@med.umich.edu | |
| Principal Investigator: John Heckenlively, MD | |
| United States, Oregon | |
| Oregon Health & Science University | Recruiting |
| Portland, Oregon, United States, 97239 | |
| Contact: Catie Beattie, MS 503-494-2363 beattie@ohsu.edu | |
| Principal Investigator: Mark Pennesi, MD | |
| United States, Tennessee | |
| University of Tennessee, Hamilton Eye Institute | Recruiting |
| Memphis, Tennessee, United States, 38163 | |
| Contact: Barbara Jennings, MA, OD 901-448-6445 bjennin5@uthsc.edu | |
| Principal Investigator: Alessandro Iannaccone, MD, MS | |
| United States, Texas | |
| Retina Foundation of the Southwest | Recruiting |
| Dallas, Texas, United States, 75231 | |
| Contact: Kirsten Locke, RN 214-363-3911 ext 114 kglocke@retinafoundation.org | |
| Principal Investigator: David G Birch, PhD | |
| United States, Utah | |
| University of Utah School of Medicine, Moran Eye Center | Recruiting |
| Salt Lake City, Utah, United States, 84132 | |
| Contact: Kimberley Wegner, RN 801-581-6265 Kimberley.Wegner@hsc.utah.edu | |
| Principal Investigator: Paul S Bernstein, MD, PhD | |
| Study Director: | Judith Chiostri, MS | National Neurovision Research Institute |
More Information
Additional Information:
Publications:
| Responsible Party: | National Neurovision Research Institute |
| ClinicalTrials.gov Identifier: | NCT01233609 History of Changes |
| Other Study ID Numbers: | H-13371 |
| Study First Received: | November 1, 2010 |
| Last Updated: | April 5, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Neurovision Research Institute:
|
retinitis pigmentosa valproic acid visual field |
Additional relevant MeSH terms:
|
Retinitis Retinitis Pigmentosa Retinal Diseases Eye Diseases Eye Diseases, Hereditary Retinal Dystrophies Retinal Degeneration Genetic Diseases, Inborn Valproic Acid Anticonvulsants Central Nervous System Agents |
Therapeutic Uses Pharmacologic Actions Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action GABA Agents Neurotransmitter Agents Physiological Effects of Drugs Antimanic Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs |
ClinicalTrials.gov processed this record on May 19, 2013