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

描述(由申请人提供)：通过抗醇溶蛋白抗体测定，精神分裂症患者对面筋的敏感性(约20%-30%)约是普通人群(约3%-5%)的5-6倍。面筋敏感性(GS)与一系列行为和神经精神障碍有关。之前大多数无麸质饮食的临床试验都显示，对精神分裂症患者的一小部分受试者有显著的益处；小规模的非确认性试验可能是由抽样差异和面筋敏感性的相对稀有性解释的：也就是说，在一些试验中，样本包括很少或没有预期受益的受试者。对所有结果的综合解释是，在GS亚群中摄入小麦会触发免疫反应，从而影响中枢神经系统，并产生精神分裂症的症状。之前申请无麸质饮食治疗精神分裂症的双盲随机对照试验得到的优先分数为5分，百分位数为18分，不足以资助。这项发展工作申请是为了回应审查人员的批评，他们担心招募工作的可行性、在试验的住院阶段留住受试者的能力以及受试者在试验的住院阶段完成后维持饮食的能力。我们的计划是 从八个不同的潜在受试者来源中抽样，以评估哪些是最有效地提供合格和热情的受试者，并制定程序，最大限度地成功招募到为期4周的住院试验中。对面筋敏感的20名受试者的试点试验将在马里兰精神病学研究中心的住院治疗单元进行，这将支付住院治疗的费用。治疗组和对照组将接受无面筋饮食，其中治疗组添加非面筋淀粉，对照组添加外观相同的面筋。受试者和评价者将对实验条件视而不见。在这一阶段制定的程序将有助于在未来的全面试验中最大限度地保留。A两个 住院后一个月的维持阶段将制定程序，最大限度地坚持无麸质饮食，并评估在这一延长时期的好处。要评估的评估包括总体症状的BPRS量表，阴性症状的SANS，认知功能的Matrics，胃肠道症状的CSI和GSRs，以及一系列免疫参数。在美国，大约有150万人患有精神分裂症，其中约20%-30万人-对面筋敏感。半个多世纪以来，精神分裂症治疗的基本假设没有改变，需要新的治疗方法。这项研究解决了NIH通过为精神分裂症人群的一部分开发有针对性的治疗来推进个性化药物的目标。结果将有助于阐明病因途径。一种廉价且无危险的有效治疗方法，如无麸质饮食，将对公众健康产生深远的好处。

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.