A Genetic Survey of Cytochrome P450 2D6 Genotypes by Nanopore DNA Sequencing and Clinical Response to Codeine and Tramadol in Postoperative Pain Management
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- CYP2D6 genotypes/phenotypes
研究概览
简要总结
Codeine is one of the most commonly prescribed opioids in the world. The speed at which our liver metabolizes codeine into morphine depends on an important protein called cytochrome P450 2D6 (CYP2D6). Many people across the world have different CYP2D6 metabolizing speeds. Codeine provides inadequate pain management to those who have slow-metabolizing CYP2D6. In contrast, codeine can be life-threatening to those who have rapidly-metabolizing CYP2D6 because of the abruptly high dose of morphine. By analyzing specific genes, we are able to predict a patient's response to medication, thus drug type and dosing can be tailored according to their genetics. The purpose of this study is to observe if nanopore CYP2D6 DNA genetic sequencing can classify patients according to their CYP2D6 phenotype and thus predict their response to codeine and tramadol. The overall project is to determine the practicality of a genetic survey of CYP2D6 for healthy patients undergoing surgical procedures.
详细描述
PURPOSE: The purpose of this study is to investigate if genetic variants of CYP2D6 are a predictive factor for postoperative pain management with conventional codeine and tramadol pain therapy. With CYP2D6 DNA analysis, we hope to be able to correlate a patients' genetics and their physiological response to conventional codeine and tramadol dosing.
RESEARCH QUESTION: Is CYP2D6 metabolizer status a predictive factor for the effectiveness of postoperative pain management with conventional pain therapy doses of codeine and tramadol?
HYPOTHESIS: Our hypothesis is that patients with known rapid metabolizing CYP2D6 variants will have higher incidences of opioid side effects with conventional opioid dosing. On the other hand, patients with known poor-metabolizing CYP2D6 variants will have inadequate pain management with conventional opioid dosing.
JUSTIFICATION: Understanding the relationship between CYP2D6 variants and conventional opioid dosing in a clinical setting will facilitate future studies that investigate personalized dosing in order to improve pain management and reduce risk of opioid side effects.
OBJECTIVES: The primary objective of this study is to determine the practicality of undertaking a medium-scale genetic survey of CYP2D6 for healthy patients undergoing surgical procedures. Secondary objectives include: investigate the feasibility of characterizing CYP2D6 genetic variants into one of four metabolizer groups, investigate if there is a distinguishable pattern between CYP2D6 metabolizer status and postoperative pain management quality with conventional pain therapy dosages such as codeine and tramadol, investigate if there is a distinguishable pattern between CYP2D6 metabolizer status and the presence of opioid side effects with conventional pain therapy dosages such as codeine and tramadol, to raise awareness of the clinical relevance of CYP2D6 variants on codeine and tramadol metabolism as well as the complications that arise from conventional, non-personalized pain management.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-55 year and otherwise healthy (ASA 1 or 2)
- •Undergoing an elective outpatient surgical procedure at Royal Columbian Hospital or Eagle Ridge Hospital with projected moderate post-operative pain
- •Surgical procedure that requires general anaesthetic and post-operative pain management routinely managed with either codeine or tramadol by attending surgeon (i.e., ACL repair)
- •Attending surgeon routinely prescribes either tramadol or codeine for post-operative pain management
排除标准
- •Pre-existing chronic pain condition
- •Any psychiatric diagnosis, such as depression or anxiety (Lautenbacher et al., 1994)
- •History of substance abuse/dependence
- •Multiple medical comorbidities (a single well-controlled medical comorbidity will not be a contraindication - i.e., controlled hypothyroidism)
- •Allergy, sensitivity, or other contraindication to either codeine or tramadol
- •Regional anesthetic (inclusive either of a major peripheral nerve block or neuraxial anesthetic) planned by attending anesthesiologist)
- •Unable to provide informed consent
结局指标
主要结局
CYP2D6 genotypes/phenotypes
时间窗: 6 months
CYP2D6 genotype determined by nanopore DNA sequencing which will be cross-referenced with published genotypes to determine CYP2D6 phenotype
次要结局
- Total opiate consumption(6 months)
- Pain scores(6 months)
- Sedation level(6 months)
- Administration of anti-nausea medications(6 months)
- Postoperative Day 1 current pain and worst pain since discharge(6 months)
- Postoperative Day 1 Nausea and vomiting (Yes/No, dichotomous)(6 months)
- Total opioids taken since discharge(6 months)
研究者
Perseus Missirlis
Clinical Instructor
Fraser Health