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

麦醇溶蛋白阳性精神分裂症无麸质饮食随机对照试验的发展

• 批准号: 8877631
• 负责人: WILLIAM W EATON
• 金额: $ 19.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8877631
• 关键词: Address; Adherence; Admission activity; Affect; Antibodies; Behavioral; Biological Assay; Biological Markers; Blinded; Caring; Celiac Disease; China; Clinical Trials; Complex; Control Groups; Critiques; Development; Diet; Disease; Double-Blind Method; Environment; Functional disorder; Funding; Future; General Population; Gliadin; Gluten; Goals; Guidelines; Health; Health Benefit; Immune; Immune system; Individual; Ingestion; Inpatients; Intervention; Location; Maintenance; Maryland; Measures; Methods; Monitor; Nature; Neuraxis; Neurologic; Norway; Outpatients; Participant; Pathway interactions; Patients; Persons; Phase; Phenotype; Placebos; Population; Prevalence; Procedures; Psychopathology; Public Health; Randomized Controlled Trials; Reaction; Recruitment Activity; Relative (related person); Reporting; Research; Residential Treatment; Risk; Sampling; Schizophrenia; Source; Starch; Subgroup; Symptoms; Syndrome; Taiwan; Testing; Time; Tunisia; United States; United States National Institutes of Health; Variant; Wheat; Withdrawal; Work; blind; clinically significant; cognitive function; cohort; cost; design; effective therapy; gastrointestinal symptom; improved; interest; neuropsychiatry; personalized medicine; pilot trial; success; targeted treatment

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.

描述（由申请人提供）：通过抗麦醇溶蛋白抗体测量，精神分裂症患者对麸质的敏感性（约 20-30%）比普通人群（约 3-5%）高出约 5 或 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都揭示了对精神分裂症患者亚群的巨大益处。小型非证实性试验可能是由于抽样差异和麸质敏感性的相对稀有性来解释的：也就是说，一些试验中的样本很少或根本没有预期受益的受试者。对所有结果的综合解释是，GS个体亚群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的症状。 先前申请的一项无麸质饮食治疗精神分裂症的双盲随机对照试验获得了 5 分的优先评分和 18 分的百分位等级，不足以获得资助。这项开发工作的申请是对审稿人的批评的回应，审稿人担心招募工作的可行性、在试验的住院阶段保留受试者的能力以及受试者在试验的住院阶段完成后维持饮食的能力。 计划是 从八个不同来源的潜在受试者中进行抽样，评估哪些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进入为期 4 周的住院试验。对麸质敏感的 20 名受试者进行的试点规模试验将在马里兰州精神病学研究中心的住院治疗室进行，该试验将支付住院治疗费用。治疗组和对照组将接受无麸质饮食，其中治疗组添加非麸质淀粉，对照组添加外观相同的麸质。受试者和评估者将对实验条件视而不见。此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。一个二 住院期后的一个月维持阶段将制定程序，以最大限度地坚持无麸质饮食，并评估在此延长期间的益处。待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，精神分裂症影响着大约 150 万人，而这 30 万人中大约有 20% 对麸质过敏。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。这项研究实现了 NIH 通过为一部分精神分裂症人群开发针对性治疗来推进个性化医疗的目标。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，例如无麸质饮食，将对公共健康产生深远的益处。

项目成果

Kynurenine and Tryptophan Levels in Patients With Schizophrenia and Elevated Antigliadin Immunoglobulin G Antibodies.

精神分裂症患者的犬尿氨酸和色氨酸水平以及抗麦胶蛋白免疫球蛋白 G 抗体升高。

• DOI: 10.1097/psy.0000000000000352
• 发表时间: 2016
• 期刊: Psychosomatic medicine
• 影响因子: 3.3
• 作者: Okusaga,Olaoluwa;Fuchs,Dietmar;Reeves,Gloria;Giegling,Ina;Hartmann,AnnetteM;Konte,Bettina;Friedl,Marion;Groer,Maureen;Cook,ThomasB;Stearns-Yoder,KellyA;Pandey,JanardanP;Kelly,DeannaL;Hoisington,AndrewJ;Lowry,ChristopherA

Gluten sensitivity and relationship to psychiatric symptoms in people with schizophrenia.

• DOI: 10.1016/j.schres.2014.09.023
• 发表时间: 2014-11
• 期刊: SCHIZOPHRENIA RESEARCH
• 影响因子: 4.5
• 作者: Jackson, Jessica;Eaton, William;Cascella, Nicola;Fasano, Alessio;Santora, Debby;Sullivan, Kelli;Feldman, Stephanie;Raley, Heather;McMahon, Robert P.;Carpenter, William T., Jr.;Demyanovich, Haley;Kelly, Deanna L.
• 通讯作者: Kelly, Deanna L.