Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
90 participants
INTERVENTIONAL
2010-11-30
2015-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Valproic Acid
Subjects who receive valproic acid
Valproic Acid
One to four 250mg softgels by mouth daily (dose determined by body weight)
Placebo
Subjects who receive placebo
Placebo
Dosage per subject weight- same schedule as the active comparator
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Valproic Acid
One to four 250mg softgels by mouth daily (dose determined by body weight)
Placebo
Dosage per subject weight- same schedule as the active comparator
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
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
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.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
United States Department of Defense
FED
Foundation Fighting Blindness
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Patricia Zilliox, PhD
Role: STUDY_DIRECTOR
Foundation Fighting Blindness
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Miami, Bascom Palmer Eye Institute
Miami, Florida, United States
University of Michigan, Ann Arbor
Ann Arbor, Michigan, United States
Oregon Health & Science University
Portland, Oregon, United States
University of Tennessee, Hamilton Eye Institute
Memphis, Tennessee, United States
Retina Foundation of the Southwest
Dallas, Texas, United States
University of Utah School of Medicine, Moran Eye Center
Salt Lake City, Utah, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Berson EL, Rosner B, Weigel-DiFranco C, Dryja TP, Sandberg MA. Disease progression in patients with dominant retinitis pigmentosa and rhodopsin mutations. Invest Ophthalmol Vis Sci. 2002 Sep;43(9):3027-36.
Bryant AE 3rd, Dreifuss FE. Valproic acid hepatic fatalities. III. U.S. experience since 1986. Neurology. 1996 Feb;46(2):465-9. doi: 10.1212/wnl.46.2.465.
Berson EL, Sandberg MA, Rosner B, Birch DG, Hanson AH. Natural course of retinitis pigmentosa over a three-year interval. Am J Ophthalmol. 1985 Mar 15;99(3):240-51. doi: 10.1016/0002-9394(85)90351-4.
Chen PS, Wang CC, Bortner CD, Peng GS, Wu X, Pang H, Lu RB, Gean PW, Chuang DM, Hong JS. Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity. Neuroscience. 2007 Oct 12;149(1):203-12. doi: 10.1016/j.neuroscience.2007.06.053. Epub 2007 Jul 28.
Delyfer MN, Leveillard T, Mohand-Said S, Hicks D, Picaud S, Sahel JA. Inherited retinal degenerations: therapeutic prospects. Biol Cell. 2004 May;96(4):261-9. doi: 10.1016/j.biolcel.2004.01.006.
Dragunow M, Greenwood JM, Cameron RE, Narayan PJ, O'Carroll SJ, Pearson AG, Gibbons HM. Valproic acid induces caspase 3-mediated apoptosis in microglial cells. Neuroscience. 2006 Jul 21;140(4):1149-56. doi: 10.1016/j.neuroscience.2006.02.065.
Gaby AR. Nutritional therapies for ocular disorders: Part Three. Altern Med Rev. 2008 Sep;13(3):191-204.
Gottlicher M, Minucci S, Zhu P, Kramer OH, Schimpf A, Giavara S, Sleeman JP, Lo Coco F, Nervi C, Pelicci PG, Heinzel T. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J. 2001 Dec 17;20(24):6969-78. doi: 10.1093/emboj/20.24.6969.
Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006 Nov 18;368(9549):1795-809. doi: 10.1016/S0140-6736(06)69740-7.
Henry TR. The history of valproate in clinical neuroscience. Psychopharmacol Bull. 2003;37 Suppl 2:5-16.
Hoffman DR, Locke KG, Wheaton DH, Fish GE, Spencer R, Birch DG. A randomized, placebo-controlled clinical trial of docosahexaenoic acid supplementation for X-linked retinitis pigmentosa. Am J Ophthalmol. 2004 Apr;137(4):704-18. doi: 10.1016/j.ajo.2003.10.045.
Jacobson SG, Cideciyan AV, Huang Y, Hanna DB, Freund CL, Affatigato LM, Carr RE, Zack DJ, Stone EM, McInnes RR. Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene. Invest Ophthalmol Vis Sci. 1998 Nov;39(12):2417-26.
Kim HJ, Rowe M, Ren M, Hong JS, Chen PS, Chuang DM. Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action. J Pharmacol Exp Ther. 2007 Jun;321(3):892-901. doi: 10.1124/jpet.107.120188. Epub 2007 Mar 19.
Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD; National Eye Institute Visual Function Questionnaire Field Test Investigators. Development of the 25-item National Eye Institute Visual Function Questionnaire. Arch Ophthalmol. 2001 Jul;119(7):1050-8. doi: 10.1001/archopht.119.7.1050.
Noorwez SM, Ostrov DA, McDowell JH, Krebs MP, Kaushal S. A high-throughput screening method for small-molecule pharmacologic chaperones of misfolded rhodopsin. Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3224-30. doi: 10.1167/iovs.07-1539. Epub 2008 Mar 31.
Nowomiejska K, Vonthein R, Paetzold J, Zagorski Z, Kardon R, Schiefer U. Comparison between semiautomated kinetic perimetry and conventional Goldmann manual kinetic perimetry in advanced visual field loss. Ophthalmology. 2005 Aug;112(8):1343-54. doi: 10.1016/j.ophtha.2004.12.047.
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.
Peterson GM, Naunton M. Valproate: a simple chemical with so much to offer. J Clin Pharm Ther. 2005 Oct;30(5):417-21. doi: 10.1111/j.1365-2710.2005.00671.x. No abstract available.
Wong R, Khan J, Adewoyin T, Sivaprasad S, Arden GB, Chong V. The ChromaTest, a digital color contrast sensitivity analyzer, for diabetic maculopathy: a pilot study. BMC Ophthalmol. 2008 Aug 17;8:15. doi: 10.1186/1471-2415-8-15.
Birch DG, Bernstein PS, Iannacone A, Pennesi ME, Lam BL, Heckenlively J, Csaky K, Hartnett ME, Winthrop KL, Jayasundera T, Hughbanks-Wheaton DK, Warner J, Yang P, Fish GE, Teske MP, Sklaver NL, Erker L, Chegarnov E, Smith T, Wahle A, VanVeldhuisen PC, McCormack J, Lindblad R, Bramer S, Rose S, Zilliox P, Francis PJ, Weleber RG. Effect of Oral Valproic Acid vs Placebo for Vision Loss in Patients With Autosomal Dominant Retinitis Pigmentosa: A Randomized Phase 2 Multicenter Placebo-Controlled Clinical Trial. JAMA Ophthalmol. 2018 Aug 1;136(8):849-856. doi: 10.1001/jamaophthalmol.2018.1171.
Related Links
Access external resources that provide additional context or updates about the study.
Click here for more information about this study: Clinical Trial page of the Foundation Fighting Blindness Website.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
H-13371
Identifier Type: -
Identifier Source: org_study_id