Camp Kathryn M, Krotoski Danuta, Parisi Melissa A, Gwinn Katrina A, Cohen Bruce H, Cox Christine S, Enns Gregory M, Falk Marni J, Goldstein Amy C, Gopal-Srivastava Rashmi, Gorman Gráinne S, Hersh Stephen P, Hirano Michio, Hoffman Freddie Ann, Karaa Amel, MacLeod Erin L, McFarland Robert, Mohan Charles, Mulberg Andrew E, Odenkirchen Joanne C, Parikh Sumit, Rutherford Patricia J, Suggs-Anderson Shawne K, Tang W H Wilson, Vockley Jerry, Wolfe Lynne A, Yannicelli Steven, Yeske Philip E, Coates Paul M
Office of Dietary Supplements, National Institutes of Health, Bethesda, MD 20892, USA.
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Mol Genet Metab. 2016 Nov;119(3):187-206. doi: 10.1016/j.ymgme.2016.09.002. Epub 2016 Sep 20.
In December 2014, a workshop entitled "Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base" was convened at the NIH with the goals of exploring the use of nutritional interventions in primary mitochondrial disorders (PMD) and identifying knowledge gaps regarding their safety and efficacy; identifying research opportunities; and forging collaborations among researchers, clinicians, patient advocacy groups, and federal partners. Sponsors included the NIH, the Wellcome Trust, and the United Mitochondrial Diseases Foundation. Dietary supplements have historically been used in the management of PMD due to their potential benefits and perceived low risk, even though little evidence exists regarding their effectiveness. PMD are rare and clinically, phenotypically, and genetically heterogeneous. Thus patient recruitment for randomized controlled trials (RCTs) has proven to be challenging. Only a few RCTs examining dietary supplements, singly or in combination with other vitamins and cofactors, are reported in the literature. Regulatory issues pertaining to the use of dietary supplements as treatment modalities further complicate the research and patient access landscape. As a preface to exploring a research agenda, the workshop included presentations and discussions on what PMD are; how nutritional interventions are used in PMD; challenges and barriers to their use; new technologies and approaches to diagnosis and treatment; research opportunities and resources; and perspectives from patient advocacy, industry, and professional organizations. Seven key areas were identified during the workshop. These areas were: 1) defining the disease, 2) clinical trial design, 3) biomarker selection, 4) mechanistic approaches, 5) challenges in using dietary supplements, 6) standards of clinical care, and 7) collaboration issues. Short- and long-term goals within each of these areas were identified. An example of an overarching goal is the enrollment of all individuals with PMD in a natural history study and a patient registry to enhance research capability. The workshop demonstrates an effective model for fostering and enhancing collaborations among NIH and basic research, clinical, patient, pharmaceutical industry, and regulatory stakeholders in the mitochondrial disease community to address research challenges on the use of dietary supplements in PMD.
2014年12月，美国国立卫生研究院（NIH）召开了一场题为“原发性线粒体疾病的营养干预：建立证据基础”的研讨会，其目标是探讨营养干预在原发性线粒体疾病（PMD）中的应用，并确定有关其安全性和有效性的知识空白；确定研究机会；以及促成研究人员、临床医生、患者权益倡导组织和联邦合作伙伴之间的合作。主办方包括美国国立卫生研究院、惠康基金会和联合线粒体疾病基金会。尽管关于膳食补充剂有效性的证据很少，但由于其潜在益处和较低的风险认知，膳食补充剂在历史上一直被用于PMD的管理。PMD很罕见，在临床、表型和基因方面具有异质性。因此，事实证明招募患者进行随机对照试验（RCT）具有挑战性。文献中仅报道了少数几项研究膳食补充剂单独使用或与其他维生素及辅助因子联合使用的随机对照试验。将膳食补充剂用作治疗方式的监管问题进一步使研究和患者获取情况变得复杂。作为探索研究议程的前言，研讨会包括了关于以下内容的报告和讨论：什么是PMD；营养干预在PMD中如何使用；其使用的挑战和障碍；诊断和治疗的新技术和方法；研究机会和资源；以及患者权益倡导组织、行业和专业组织的观点。研讨会期间确定了七个关键领域。这些领域是：1）疾病定义，2）临床试验设计，3）生物标志物选择，4）机制研究方法，5）使用膳食补充剂的挑战，6）临床护理标准，7）合作问题。确定了这些领域中每个领域的短期和长期目标。一个总体目标的例子是将所有PMD患者纳入一项自然史研究和一个患者登记系统，以提高研究能力。该研讨会展示了一种有效的模式，可促进和加强美国国立卫生研究院与线粒体疾病领域的基础研究、临床、患者、制药行业及监管利益相关者之间的合作，以应对在PMD中使用膳食补充剂的研究挑战。
