Understanding the Association between Sublingual Buprenorphine and Oral Health Outcomes

了解舌下含服丁丙诺啡与口腔健康结果之间的关联

• 批准号: 10765299
• 负责人: Douglas Oyler
• 金额: $ 135.65万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-21 至 2025-09-20
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10765299
• 关键词: 16S ribosomal RNA sequencing; Acids; Address; Adult; Adverse event; Affect; American; Anti-Cholinergics; Behavioral; Buffers; Buprenorphine; Case Study; Characteristics; Clinical; Cohort Studies; Complication; Confounding Factors (Epidemiology); Data; Decayed, Missing, and Filled Teeth; Dental; Dental Hygiene; Dental Plaque Index; Dental caries; Dentistry; Development; Diet; Disease; Disease Outcome; Disease Progression; Economic Burden; Enrollment; Environment; Epidemiology; Event; Fracture; Goals; Half-Life; Health; Health Services Accessibility; Hemorrhage; High Prevalence; Hour; Immune response; Immunology; Immunosuppression; Incidence; Individual; Inflammatory; Inflammatory Response; Kentucky; Link; Literature; Longitudinal Studies; Measurement; Measures; Mediator; Methadone; Mouth Diseases; Naltrexone; North Carolina; Onset of illness; Opioid; Opioid agonist; Oral; Oral health; Outcome; Participant; Patient Self-Report; Patients; Periodontal Diseases; Persons; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Physiological; Population; Property; Prospective, cohort study; Publishing; Questionnaires; Recommendation; Recording of previous events; Recovery; Reporting; Research; Research Design; Research Personnel; Risk; Risk Factors; Saliva; Salivary; Sample Size; Severities; Site; Smoking; Standardization; Testing; Time; Tooth Attrition; Tooth Loss; Tooth structure; United States Food and Drug Administration; Visit; absorption; bacterial community; behavioral health; burden of illness; comparison group; cytokine; design; evidence base; follow-up; high risk; implementation facilitation; implementation intervention; improved; indexing; individual response; innovation; insight; lifestyle factors; medication for opioid use disorder; microbial; microbiome; mortality; multidisciplinary; multiple drug use; neglect; opioid epidemic; opioid overdose; opioid use disorder; oral infection; oral microbiome; overdose death; pathogenic bacteria; pharmacologic; preventive intervention; prospective; radiological imaging; standard care

ABSTRACT The standard treatment for opioid use disorder (OUD) involves the use of medications (MOUD), primarily sublingual (SL) buprenorphine due to its accessibility, efficacy, and tolerability. However, recently the Food and Drug Administration (FDA) published an advisory suggesting SL buprenorphine use is linked to oral disease. While compelling, this advisory is based on adverse event reports and case reports that did control for important confounders such as behavioral and lifestyle factors that may increase the risk in individuals with OUD. More so, these reports were cross-sectional providing limited evidence of rate of progression and incidence of new disease. Additionally, the mechanism by which SL buprenorphine may adversely impact oral health remains unclear. The long-term goal of this project is to quantify adverse oral events associated with SL buprenorphine, facilitating implementation of interventions and practice recommendations to mitigate the burden of oral complications in adults taking SL buprenorphine. The objective of this proposal is to understand if and how SL buprenorphine increases the extent, onset, and progression of oral disease in adults with OUD. Our central hypothesis is that SL buprenorphine causes alterations in the oral environment (e.g., reduction in salivary flow/pH/buffer capacity and microbiome and inflammatory host response changes) that facilitate the incidence and progression of oral disease. We will test this hypothesis with three aims: 1) characterize baseline extent of oral complication and identify risk factors in adults receiving MOUD, 2) test whether SL buprenorphine is a risk factor for oral disease onset and progression in adults taking MOUD, and 3) assess whether SL buprenorphine changes saliva quantity, composition, microbial profile, or inflammatory host response in adults taking MOUD. To accomplish these aims, we propose a prospective, multisite, cohort study across Kentucky and North Carolina, leveraging a multidisciplinary team of researchers and clinicians to overcome the limitations identified in the literature and expand our understanding of the link between SL buprenorphine and oral disease. We will enroll 372 participants across two states that have been highly impacted by the opioid epidemic and evaluate clinical, radiographic, physiologic, and behavioral information over an 8-month follow-up period. This study is innovative as it is the first one to: conduct longitudinal follow-up, utilize a comparison MOUD group, and analyze salivary characteristics to clarify the mechanisms of sublingual buprenorphine-induced disease and will quantify the bacterial composition and inflammatory response and correlate to clinical findings. The proposed research is significant because it will generate data-driven conclusions about the risks associated with oral disease extent, onset, and progression in adults taking SL buprenorphine. These findings can be used to develop preventive interventions to reduce the burden of oral disease and improve health in this population.

摘要 阿片类药物使用障碍(OUD)的标准治疗包括使用药物(Moud)，主要是 舌下(SL)丁丙诺啡，因其可及性、有效性和耐受性。然而，最近食品和 美国药品监督管理局(FDA)发布了一份咨询报告，表明SL丁丙诺啡的使用与口腔疾病有关。 虽然很有说服力，但这一建议是基于不良事件报告和案例报告，这些报告确实控制了重要的 混杂因素，如行为和生活方式因素，可能会增加OUD患者的风险。更重要的是， 这些报告都是横断面的，提供了有限的证据来证明新的 疾病。此外，SL丁丙诺啡可能对口腔健康产生不利影响的机制仍然存在 不清楚。该项目的长期目标是量化与SL丁丙诺啡相关的不良口腔事件， 促进实施减轻口语负担的干预措施和练习建议 成人服用丁丙诺啡的并发症。这项建议的目标是了解是否以及如何 丁丙诺啡增加成人口腔疾病的程度、发病和进展。我们的中央 假设SL丁丙诺啡导致口腔环境的改变(例如，唾液减少 流量/pH/缓冲能力、微生物群和炎性宿主反应的变化)促进了发病 以及口腔疾病的进展。我们将通过三个目标来检验这一假设：1)描述基线程度 接受MOD治疗的成人口腔并发症和危险因素2)测试SL丁丙诺啡是否有风险 服用Moud的成人口腔疾病发生和进展的因素，以及3)评估SL丁丙诺啡 改变服用Moud的成人的唾液量、成分、微生物分布或炎症宿主反应。 为了实现这些目标，我们建议在肯塔基州和北部进行一项前瞻性的、多点的队列研究 卡罗莱纳州，利用一个由研究人员和临床医生组成的多学科团队来克服确定的限制 并扩大我们对SL丁丙诺啡与口腔疾病之间联系的理解。我们会 在受阿片类药物流行影响较大的两个州招募372名参与者，并评估 在8个月的随访期内提供临床、放射学、生理和行为信息。这项研究是 创新因为它是第一个：进行纵向跟踪，利用对照Moud小组，并分析 唾液特征，以阐明舌下丁丙诺啡诱发疾病的机制，并将量化 细菌组成和炎症反应与临床表现相关。拟议的研究 意义重大，因为它将生成关于口腔疾病相关风险的数据驱动的结论 成人服用丁丙诺啡的范围、发病和进展。这些发现可以用来开发 采取预防性干预措施，减轻口腔疾病负担，改善这一人群的健康状况。