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

基本信息

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
项目类别：
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

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

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项目摘要

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.

抽象的阿片类药物使用障碍（OUD）的标准治疗方法涉及使用药物（MOUD）舌下（SL）丁丙诺啡由于其可及性，功效和耐受性。但是，最近食物和药物管理局（FDA）发表了一项建议，表明使用SL丁丙诺啡与口腔疾病有关。在引人入胜的同时，此咨询是基于不利事件报告和案例报告，这些报告确实控制着重要诸如行为和生活方式因素之类的混杂因素可能会增加OUD患者的风险。更重要的是这些报告是横截面的，提供了有限的新进展和发生率的证据疾病。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，促进实施干预措施和实践建议，以减轻口服负担服用SL丁丙诺啡的成年人的并发症。该提议的目的是了解是否以及如何 SL丁丙诺啡增加OUD成人口腔疾病的程度，发作和进展。我们的中心假设是SL丁丙诺啡会导致口服环境的改变（例如，唾液减少流量/pH/缓冲能力，微生物组和炎症宿主反应变化），促进发生率和口腔疾病的进展。我们将以三个目的检验该假设：1）表征的基线范围口服并发症并确定接受MOUD的成年人的危险因素，2）测试SL丁丙诺啡是否是风险成年人口腔疾病发作和进展的因子，以及3）评估SL丁丙诺啡是否在服用MOUD的成年人中会改变唾液数量，成分，微生物谱或炎症宿主反应。为了实现这些目标，我们建议在肯塔基州和北卡罗来纳州，利用研究人员和临床医生组成的多学科团队克服所确定的局限性在文献中，并扩展了我们对SL丁丙诺啡与口腔疾病之间联系的理解。我们将在两个州的372名参与者招募受阿片类药物流行高度影响并评估的参与者在8个月的随访期间，临床，射线照相，生理和行为信息。这项研究是创新性是第一个进行：进行纵向随访，使用比较组，并分析唾液特征以阐明舌下丁丙诺啡诱导的疾病的机制，并将量化细菌组成和炎症反应与临床发现相关。拟议的研究之所以重要，是因为它将对与口腔疾病相关的风险产生数据驱动服用SL丁丙诺啡的成年人的程度，发作和进展。这些发现可用于发展预防干预措施减轻口腔疾病负担并改善该人群的健康。