A Novel Diagnostic Test to Detect Vitamin B12 Deficiency

描述（由申请人提供）：维生素B12缺乏症是一种常见的问题，影响到普通美国人，尤其是老年人。老年人有临床前维生素B12缺乏的风险，因为随着年龄的增长，维生素B12吸收不良和萎缩性胃炎的发生率增加。老年人缺乏维生素B12有潜在的严重并发症，包括痴呆、阿尔茨海默病和癌症。目前诊断B12缺乏症的方法是不充分的，因为它们缺乏特异性，有不明确的参考范围或昂贵。我们提出的测试，被称为B12呼吸测试（BBT），将具有非侵入性，易于管理和保质期长的优点。BBT将使医生能够以比目前的诊断测试低得多的成本准确地检测出B12缺乏症。我们的目标是在临床前阶段确定维生素B12缺乏症，此时治疗可以避免并发症。诊断这种缺乏症是有意义的，因为一旦确定是一个问题，就可以通过适当的维生素B12补充剂进行有效而廉价的治疗。这将导致较低的总体医疗费用，因为这种情况可以迅速识别和适当治疗。该测试的基本科学原理是丙酸盐的代谢受到维生素B12可用性的限制。因此，在口服13c（非放射性）标记丙酸的示踪剂剂量后，与B12正常状态的个体相比，维生素B12缺乏个体呼吸中的13co2量减少。第一阶段的拨款证明了这一概念的可行性。在第二阶段，我们将以降低测试成本和简化测试为目标来完善测试程序。具体来说，我们将检查小剂量丙酸，单次20分钟呼气收集，并消除禁食状态超过1小时的需要。第三阶段后的最终产品将是FDA批准的诊断试剂盒。该试剂盒将出售给我们目前的临床实验室客户，其他独立的临床实验室和1000多家拥有即时呼吸测试设备的医师实验室。

DESCRIPTION (provided by applicant): Vitamin B12 deficiency is a common problem that affects the general US population and the elderly in particular. The elderly are at risk for preclinical vitamin B12 deficiency due to the increased presence of B12 malabsorption and atrophic gastritis as a consequence of aging. The deficiency of vitamin B12 in the elderly has potentially serious complications including dementia, Alzheimer's disease, and cancer. Current approaches to diagnosing B12 deficiency are inadequate because they lack specificity, have poorly defined reference ranges or are expensive. Our proposed test, known as the B12 Breath Test (BBT), will have the advantage of being non-invasive, be easy to administer and have a long shelf life. The BBT will allow physicians to accurately test for B12 deficiency at a much lower cost than current diagnostic tests. Our goal is to identify vitamin B12 deficiency in a preclinical stage when treatment can avert complications. Diagnosing this deficiency is meaningful because once identified as a problem, it can be effectively and inexpensively treated with appropriate vitamin B12 supplementation. This will lead to lower overall medical costs as this condition is quickly identified and appropriately treated. The underlying scientific principle of the test is that the metabolism of propionate is limited by the availability of vitamin B12. Thus, after orally administering a tracer dose of 13 C (non-radioactive) labeled propionate, the amount of 13 CO2 is reduced in the breath of vitamin B12 deficient individuals compared to those individuals with normal B12 status. The phase I grant demonstrated the feasibility of this concept. In Phase II we will refine the testing procedure with the goal to reduce test costs and simplify the test. Specifically, we will examine a smaller dose of propionate, a single 20-minute breath collection and eliminate the need to be in a fasted state for greater than 1 hour. The final product developed after Phase III will be an FDA approved diagnostic kit. This kit will be sold to our current clinical laboratory customers, to other independent clinical labs and to the more than 1,000 physician laboratories that have point-of-care breath testing equipment. Project Narrative: Vitamin B12 deficiency is a common problem found in the elderly that is difficult to identify early because there isn't an accurate and low cost diagnostic test. The deficiency of vitamin B12 has potentially serious complications including dementia, Alzheimer's disease, and cancer. The proposed test will address this diagnostic need and lead to better quality of life for these patients because vitamin B12 deficiency can be easily and inexpensively treated with vitamin supplements.