TY - JOUR
T1 - Effect of oral valproic acid vs placebo for vision loss in patients with autosomal dominant retinitis pigmentosa a randomized phase 2 multicenter placebo-controlled
AU - Birch, David G.
AU - Bernstein, Paul S.
AU - Iannacone, Alessandro
AU - Pennesi, Mark E.
AU - Lam, Byron L.
AU - Heckenlively, John
AU - Csaky, Karl
AU - Hartnett, Mary Elizabeth
AU - Winthrop, Kevin L.
AU - Jayasundera, Thiran
AU - Hughbanks-Wheaton, Dianna K.
AU - Warner, Judith
AU - Yang, Paul
AU - Fish, Gary Edd
AU - Teske, Michael P.
AU - Sklaver, Neal L.
AU - Erker, Laura
AU - Chegarnov, Elvira
AU - Smith, Travis
AU - Wahle, Aimee
AU - VanVeldhuisen, Paul C.
AU - McCormack, Jennifer
AU - Lindblad, Robert
AU - Bramer, Steven
AU - Rose, Stephen
AU - Zilliox, Patricia
AU - Francis, Peter J.
AU - Weleber, Richard
N1 - Funding Information:
This research was supported by the Foundation Fighting Blindness and the Department of Defense, Human Research Protection Office, US Army Medical Research and Materiel Command.
Funding Information:
Funding/Support: This research was supported
Publisher Copyright:
© 2018 American Medical Association. All rights reserved.
PY - 2018/8
Y1 - 2018/8
N2 - IMPORTANCE: There are no approved drug treatments for autosomal dominant retinitis pigmentosa, a relentlessly progressive cause of adult and childhood blindness. OBJECTIVES: To evaluate the potential efficacy and assess the safety of orally administered valproic acid (VPA) in the treatment of autosomal dominant retinitis pigmentosa. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, phase 2, prospective, interventional, placebo-controlled, double-masked randomized clinical trial. The study took place in 6 US academic retinal degeneration centers. Individuals with genetically characterized autosomal dominant retinitis pigmentosa were randomly assigned to receive treatment or placebo for 12 months. Analyses were intention-to-treat. INTERVENTIONS: Oral VPA 500 mg to 1000 mg daily for 12 months or placebo. MAIN OUTCOMES AND MEASURES:The primary outcome measure was determined prior to study initiation as the change in visual field area (assessed by the III4e isopter, semiautomated kinetic perimetry) between baseline and month 12. RESULTS: The mean (SD) age of the 90 participants was 50.4 (11.6) years. Forty-four (48.9%) were women, 87 (96.7%) were white, and 79 (87.8%) were non-Hispanic. Seventy-nine participants (87.8%) completed the study (42 [95.5%] received placebo and 37 [80.4%] received VPA). Forty-two (46.7%) had a rhodopsin mutation. Most adverse events were mild, although 7 serious adverse events unrelated to VPA were reported. The difference between the VPA and placebo arms for mean change in the primary outcome was −150.43 degree2 (95% CI, −290.5 to −10.03; P = .035). CONCLUSIONS AND RELEVANCE: This negative value indicates that the VPA arm had worse outcomes than the placebo group. This study brings to light the key methodological considerations that should be applied to the rigorous evaluation of treatments for these conditions. This study does not provide support for the use of VPA in the treatment of autosomal dominant retinitis pigmentosa.
AB - IMPORTANCE: There are no approved drug treatments for autosomal dominant retinitis pigmentosa, a relentlessly progressive cause of adult and childhood blindness. OBJECTIVES: To evaluate the potential efficacy and assess the safety of orally administered valproic acid (VPA) in the treatment of autosomal dominant retinitis pigmentosa. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, phase 2, prospective, interventional, placebo-controlled, double-masked randomized clinical trial. The study took place in 6 US academic retinal degeneration centers. Individuals with genetically characterized autosomal dominant retinitis pigmentosa were randomly assigned to receive treatment or placebo for 12 months. Analyses were intention-to-treat. INTERVENTIONS: Oral VPA 500 mg to 1000 mg daily for 12 months or placebo. MAIN OUTCOMES AND MEASURES:The primary outcome measure was determined prior to study initiation as the change in visual field area (assessed by the III4e isopter, semiautomated kinetic perimetry) between baseline and month 12. RESULTS: The mean (SD) age of the 90 participants was 50.4 (11.6) years. Forty-four (48.9%) were women, 87 (96.7%) were white, and 79 (87.8%) were non-Hispanic. Seventy-nine participants (87.8%) completed the study (42 [95.5%] received placebo and 37 [80.4%] received VPA). Forty-two (46.7%) had a rhodopsin mutation. Most adverse events were mild, although 7 serious adverse events unrelated to VPA were reported. The difference between the VPA and placebo arms for mean change in the primary outcome was −150.43 degree2 (95% CI, −290.5 to −10.03; P = .035). CONCLUSIONS AND RELEVANCE: This negative value indicates that the VPA arm had worse outcomes than the placebo group. This study brings to light the key methodological considerations that should be applied to the rigorous evaluation of treatments for these conditions. This study does not provide support for the use of VPA in the treatment of autosomal dominant retinitis pigmentosa.
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U2 - 10.1001/jamaophthalmol.2018.1171
DO - 10.1001/jamaophthalmol.2018.1171
M3 - Article
C2 - 29879277
AN - SCOPUS:85051334753
SN - 2168-6165
VL - 136
SP - 849
EP - 856
JO - JAMA ophthalmology
JF - JAMA ophthalmology
IS - 8
ER -