臨床試験のエンドポイントを伝えるために,発達シナプトパシーにおける発達および行動プロファイルの特徴付け
Latha Valluripalli Soorya1, Camille W Brune1, Cristan A Farmer1
1Latha Valluripalli Soorya, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Camille W. Brune, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Cristan A. Farmer, Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, National Institutes of Health; Edith V. Ocampo, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Natalie I. Berger, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Deborah A. Pearson, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston; Robyn M. Busch, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and Department of Neurology and Epilepsy Center, Cleveland Clinic; Patricia Klaas, Center for General Neurology, Cleveland Clinic; Paige Siper, Seaver Autism Center for Research and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai; Kristn Currans, Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center; Amanda C. Gulsrud, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles; Jennifer M. Phillips, Department of Psychiatry and Behavioral Sciences, Stanford University, Rajna Filip-Dhima, Department of Neurology, Boston Children's Hospital, Harvard University; Sarah E. O'Kelley, Department of Psychology and Pediatrics, University of Alabama at Birmingham; Thomas W. Frazier, Department of Psychology, John Carroll University, Research Faculty, Departments of Pediatrics and Psychiatry at SUNY Upstate Medical University; Tess Levy, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai; Allison L. Wainer, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Joseph D. Buxbaum, Seaver Autism Center, Icahn School of Medicine at Mount Sinai; Craig M. Powell, Civitan International Research Center, University of Alabama at Birmingham; Jonathan A. Bernstein, Stanford University School of Medicine; Simon K. Warfield, Harvard University Medical School, and Department of Radiology, Boston Children's Hospital; Darcy A. Krueger, Cincinnati Children's Hospital Medical Center; E. Martina Bebin, University of Alabama at Birmingham; Hope Northrup, Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) and Children's Memorial Hermann Hospital, Shafali S. Jeste, Keck School of Medicine, University of Southern California, and Children's Hospital Los Angeles; Alexander Kolevzon, Icahn School of Medicine at Mount Sinai; Elizabeth Berry-Kravis, Rush University Medical Center; Mustafa Sahin, Department of Neurology, Boston Children's Hospital, Harvard Medical School; Siddharth Srivastava, Boston Children's Hospital and Assistant Professor of Neurology, Harvard Medical School; Audrey Thurm, Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, National Institutes of Health.
標準的な認知および行動評価は,知的障害の重症性により,フェラン-マックダーミッド症候群,結核性硬化症複合体,PTENハマルトーマ腫瘍症候群などの希少な神経遺伝疾患を有する子供にはしばしば不適切であり,臨床試験の準備に影響を与えます.
科学分野:
- 神経遺伝学
- 発達神経科学
- 臨床試験の設計
背景:
- 発達性シナプトパシーコンソーシアムは 希少な神経遺伝的症候群を研究しています
- 臨床試験の準備は重要な目標であり,検証された結果の測定が必要である.
- Phelan- McDermid症候群 (PMS),結核性硬化症複合体 (TSC),およびPTENハマルトーマ腫瘍症候群 (PHTS) は標的疾患である.
研究 の 目的:
- 現在の認知および行動評価の範囲と限界を評価する.
- 特定の神経発達状態における臨床コンセプトの試験準備度を測定する際の課題を特定する.
主な方法:
- PMS (N=98),TSC (N=98),PHTS (N=69) を患っている2~21歳の自然史研究.
- 認知と行動の測定戦略の評価
- 知的障害の重度の分析と評価の有効性への影響
主要な成果:
- 知的障害の重さは様々で,PMSでは重度から重度,TSCでは軽度から中度,PHTSでは境界線/欠席でした.
- 高度な知的障害は 自閉症診断ツールを含む 多くの標準的な評価を無効にしました
- これらの集団の現在の測定戦略で特定された制限.
結論:
- PMS,TSC,PHTSの重度の知的障害を持つ子供には,常識的および行動的な測定はしばしば不十分である.
- これらの発見は,希少な神経発達障害における臨床試験計画における重大なギャップを強調しています.
- 臨床研究と臨床試験の準備を進めていくには 評価戦略の見直しが不可欠です
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