Trial of Oral Valproic Acid for Retinitis Pigmentosa (VPA)

October 24, 2017 updated by: Foundation Fighting Blindness

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami, Bascom Palmer Eye Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • University of Michigan, Ann Arbor
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Tennessee
      • Memphis, Tennessee, United States, 38163
        • University of Tennessee, Hamilton Eye Institute
    • Texas
      • Dallas, Texas, United States, 75231
        • Retina Foundation of the Southwest
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah School of Medicine, Moran Eye Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Valproate
Placebo Comparator: Placebo
Subjects who receive placebo
Drug: Placebo
Dosage per subject weight- same schedule as the active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change in Visual Field Area From Baseline to 52 Weeks--III4e Isopter
Time Frame: baseline to week 52
Mean change in visual field area from baseline to 52 weeks. Visual field area is measured with semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haag-Streit) with the III4e target size for each eye and done at least twice to ensure reliable sessions; the visual field area measurements are averaged over the two sessions. Analysis performed with linear mixed model
baseline to week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change in Visual Field Area From Baseline to 52 Weeks--I4e Isopter
Time Frame: baseline to week 52
Mean change in visual field area from baseline to 52 weeks. Visual field area is measured with semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haag-Streit) with the I4e target size for each eye and done at least twice to ensure reliable sessions; the visual field area measurements are averaged over the two sessions. Analysis performed with linear mixed model
baseline to week 52
Static Perimetry by Treatment Arm--Full Field Hill of Vision
Time Frame: baseline to week 52
Mean change from baseline at week 52 for Full field Hill of Vision (Static perimetry)
baseline to week 52
Static Perimetry Volume--30 Degree Hill of Vision
Time Frame: baseline to week 52
Mean Change from baseline to week 52 for Static Perimetry Volume --30 Degree Hill of Vision. Full field static perimetry protocol was followed using the Octopus 900 (Haag-Streit) for a single session for each eye.
baseline to week 52
Mean Change From Baseline in Best Corrected Visual Acuity
Time Frame: baseline to week 52
Mean change in best corrected visual acuity as assessed by ETDRS (Early Treatment Diabetic Retinopathy Study) method from baseline to week 52
baseline to week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Foundation Fighting Blindness

Collaborators

United States Department of Defense

Investigators

  • Study Director: Patricia Zilliox, PhD, Foundation Fighting Blindness

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2010

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

November 1, 2010

First Submitted That Met QC Criteria

November 2, 2010

First Posted (Estimate)

November 3, 2010

Study Record Updates

Last Update Posted (Actual)

December 2, 2017

Last Update Submitted That Met QC Criteria

October 24, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-13371

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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