Development for RCT of Gluten Free Diet in Gliadin-Positive Schizophrenia

描述（由申请人提供）：抗麦胶蛋白抗体测定的麸质敏感性，在精神分裂症患者中（约20-30%）比在一般人群中（约3-5%）常见5 - 6倍。麸质敏感性（GS）与一系列行为和神经精神障碍有关。大多数先前的无麸质饮食临床试验显示，对精神分裂症患者亚组有显著的益处；小规模的非确认试验可能是由抽样差异和麸质敏感性的相对罕见来解释的：在一些试验中，样本中很少或根本没有可能受益的受试者。对所有结果的综合解释是，在GS个体亚群中摄入小麦会引发免疫反应，影响中枢神经系统并产生精神分裂症症状。先前一项关于无麸质饮食治疗精神分裂症的双盲随机对照试验申请的优先级得分为5，百分位排名为18，不足以获得资助。这项发展工作的申请是对审稿人的批评的回应，审稿人关注招募工作的可行性，在试验的住院阶段保留受试者的能力，以及在试验的住院阶段完成后受试者保持饮食的能力。计划是

DESCRIPTION (provided by applicant): Sensitivity to gluten, as measured by anti-gliadin antibodies, is about 5 or 6 times more common in persons with schizophrenia (about 20-30%) than in the general population (about 3-5%). Gluten Sensitivity (GS) is associated with a range of behavioral and neuropsychiatric disturbances. Most prior clinical trials of gluten-free diets reveal dramatic benefits for a subgroup of subjects with schizophrenia; small non-confirming trials are likely explained by sampling variation and the relative rarity of gluten sensitivity: tht is, the samples in some trials included few or no subjects who could be expected to benefit. A comprehensive interpretation for all the results is that ingestion of wheat in a subpopulation of GS individuals triggers an immune reaction which affects the central nervous system and produces the symptoms of schizophrenia. A prior application for a double-blind randomized controlled trial of a gluten-free diet for treatment of schizophrenia received a priority score of 5 and percentile rank of 18, not good enough for funding. This application for developmental work is responsive to the critiques of the reviewers who were concerned about the feasibility of the recruitment efforts, the ability to retain subjects in the inpatient phase of the trial, and the ablity of subjects to maintain the diet after the inpatient phase of the trial was completed. The plan is to sample from eight separate sources of potential subjects to evaluate which are most efficient in providing eligible and enthusiastic subjects, and to develop procedures which maximize success of recruitment into the 4-week-long inpatient trial. A pilot-size trial of gluten sensitive20 subjects will take place in a residential treatment unit at the Maryland Psychiatric Research Center, which will cover costs of inpatient treatment. Treatment and control groups will receive a gluten-free diet with addition of non-gluten starch in the treatment group and identical-appearing gluten in the control group. Subjects and assessors will be blind to the experimental condition. Procedures developed during this phase will help maximize retention in the future full trial. A two month maintenance phase after the inpatient period will develop procedures to maximize adherence to the gluten-free diet and to assess the benefits in this extended period. Assessments to be evaluated include BPRS scales for overall symptoms, SANS for negative symptoms, MATRICS for cognitive function, CSI and GSRS for gastrointestinal symptoms, and an array of immune parameters. Schizophrenia affects about 1.5 million people in the US, and about 20% of these-300,000-have gluten sensitivity. The basic hypothesis underlying treatment for schizophrenia has not changed for more than half a century, and new treatments are needed. This research addresses the NIH goal of advancing personalized medicine by developing targeted treatment for a subset of the schizophrenia population. Results would help elucidate etiologic pathways. An effective treatment that is inexpensive and without danger, such as a gluten-free diet, would have profound public health benefits.