Trial of Oral Valproic Acid for Retinitis Pigmentosa (VPA)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Foundation Fighting Blindness Clinical Research Institute
ClinicalTrials.gov Identifier:
NCT01233609
First received: November 1, 2010
Last updated: September 12, 2014
Last verified: September 2014
  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

Resource links provided by NLM:


Further study details as provided by Foundation Fighting Blindness Clinical Research Institute:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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 macular 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: December 2015
Estimated Primary Completion Date: September 2015 (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
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01233609

Locations
United States, Florida
University of Miami, Bascom Palmer Eye Institute
Miami, Florida, United States, 33136
United States, Michigan
University of Michigan, Ann Arbor
Ann Arbor, Michigan, United States, 48105
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Tennessee
University of Tennessee, Hamilton Eye Institute
Memphis, Tennessee, United States, 38163
United States, Texas
Retina Foundation of the Southwest
Dallas, Texas, United States, 75231
United States, Utah
University of Utah School of Medicine, Moran Eye Center
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Foundation Fighting Blindness Clinical Research Institute
Investigators
Study Director: Judith Chiostri, MS Foundation Fighting Blindness Clinical Research Institute
  More Information

Additional Information:
Publications:

Responsible Party: Foundation Fighting Blindness Clinical Research Institute
ClinicalTrials.gov Identifier: NCT01233609     History of Changes
Other Study ID Numbers: H-13371
Study First Received: November 1, 2010
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Foundation Fighting Blindness Clinical Research Institute:
retinitis pigmentosa
valproic acid
visual field

Additional relevant MeSH terms:
Retinitis Pigmentosa
Retinitis
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 September 22, 2014