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: 8692023
• 负责人: WILLIAM W EATON
• 金额: $ 23.59万
• 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 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8692023
• 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 Benefit; Immune; Immune system; Individual; Ingestion; Inpatients; Intervention; Location; Maintenance; Maryland; Measures; Medicine; 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; pilot trial; public health relevance; success

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（约20-30%）对谷蛋白的敏感性是一般人群（约3-5%）的5或6倍。谷蛋白敏感性（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的临床试验显示，精神分裂症受试者亚组有显着的益处;小型非确认性试验可能由抽样变异和麸质敏感性的相对罕见来解释：也就是说，一些试验中的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，GS个体亚群摄入小麦引发了影响中枢神经系统的免疫反应，并产生精神分裂症的症状。 先前申请的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的优先级评分为5分，百分位数为18，不足以获得资金。本开发工作申请是对审查员的批评的回应，审查员关注招募工作的可行性、在试验住院期保留受试者的能力以及受试者在试验住院期完成后维持饮食的能力。 该计划是 从8个不同来源的潜在受试者中取样，以评价哪一个在提供合格和热情的受试者方面最有效，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。一项对麸质敏感的20名受试者的试点试验将在马里兰州精神病学研究中心的住院治疗单位进行，该中心将支付住院治疗的费用。处理组和对照组将接受无麸质饮食，其中处理组添加非麸质淀粉，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设盲。在这一阶段制定的程序将有助于在今后的全面审判中最大限度地留住人才。两 住院期后的一个月维持期将制定程序，以最大限度地坚持无麸质饮食，并评估这一延长期的益处。待评价的评估包括用于总体症状的BPRS量表、用于阴性症状的SANS、用于认知功能的MATRICS、用于胃肠道症状的CSI和GSRS以及一系列免疫参数。 精神分裂症影响了美国约150万人，其中约20%-30万人-具有麸质敏感性。精神分裂症治疗的基本假设在超过半个世纪的时间里没有改变，需要新的治疗方法。这项研究通过为精神分裂症人群的一个子集开发靶向治疗来实现NIH推进个性化医疗的目标。结果将有助于阐明病因学途径。一种便宜且没有危险的有效治疗方法，如无麸质饮食，将对公共卫生产生深远的影响。