Effect of OPRM1 Genotype on the Dose Response to Spinal Morphine for Post-Cesarean Analgesia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 169
- 试验地点
- 2
- 主要终点
- Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively
研究概览
简要总结
HYPOTHESIS: The response to a given dose of morphine given via a spinal anesthetic for cesarean section will be affected by the genetics of the woman's mu-opioid receptor
Most women undergoing elective cesarean section (CS) receive spinal anesthesia, and most receive a dose of preservative free morphine with the spinal anesthetic. Spinally-administered morphine provides 16-24 hours of high quality pain relief. The dose administered is usually 75-200 micrograms, but surprisingly few dose-response studies exist.
The mu-opioid receptor (OPRM1 gene)is the site of action of endogenous opioid peptides and opioid analgesic drugs like morphine. There is a common genetic variant of this receptor at the 40th amino acid of the protein, with asparagine and asparate being present in different people. The less common variant (aspartate), present in 25-30% of the overall American population (higher in Asian populations, lower in Blacks) at codon 40 that has been shown in many studies to affect opioid analgesia.
This will be a randomized, blinded study of 3 doses of spinal morphine (50, 100, 150 micrograms) given to women undergoing elective cesarean section at term pregnancy. 300 women will be studied (100 per dose). Blood will be obtained for genotyping of OPRM1 and other genes that may affect pain and analgesic responses. The primary outcome will be the amount of intravenous morphine patients self-administer in the 24 hours postsurgery.
The primary outcome (use of intravenous morphine) will be analyzed by dose, and within each dose group by genotype of OPRM1. Secondary outcomes will include pain scores every 6 hours, satisfaction with analgesia, side effects (itching, nausea/vomiting) by dose and genotype.
It is anticipated that there will be an interim data analysis at 150 evaluable subjects for assessment of the dose response to morphine in the overall population; then a final analysis at 300 subjects for the genetic effect assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •healthy women undergoing elective cesarean
排除标准
- •cardiovascular disease
- •analgesic medications
- •complications of pregnancy
研究组 & 干预措施
50 micrograms (mcg) spinal morphine
Subjects will receive 50 mcg morphine in their spinal anesthetic for cesarean section
干预措施: Morphine (Drug)
100 micrograms spinal morphine
Subjects will receive 100 mcg morphine in their spinal anesthetic for cesarean section
干预措施: Morphine (Drug)
150 micrograms spinal morphine
Subjects will receive 150 mcg morphine in their spinal anesthetic for cesarean section
干预措施: Morphine (Drug)
结局指标
主要结局
Milligrams of Intravenous Morphine Used by Participant in First 24 Hours Postoperatively
时间窗: 24 hours
IV morphine use in milligrams, by participant-controlled analgesia will be assessed every 6 hours for 24 hours postoperatively.
次要结局
- Visual Analog Scale (VAS) Pain at 6 Hours(6 hours post-operatively)
- Visual Analog Scale (VAS) Pain at 12 Hours(12 hours post-operatively)
- Visual Analog Scale (VAS) Pain at 18 Hours(18 hours post-operatively)
- Visual Analog Scale (VAS) Pain at 24 Hours(24 hours post-operatively)
- Visual Analog Scale- Nausea/Vomiting at 6 Hours(6 hours post-operatively)
- Visual Analog Scale- Nausea/Vomiting at 12 Hours(12 hours post-operatively)
- Visual Analog Scale- Nausea/Vomiting at 18 Hours(18 hours post-operatively)
- Visual Analog Scale- Nausea/Vomiting at 24 Hours(24 hours post-operatively)
- Visual Analog Scale Pruritus (Itching) at 6 Hours(6 hours post-operatively)
- Visual Analog Scale Pruritus (Itching) at 12 Hours(12 hours post-operatively)
- Visual Analog Scale Pruritus (Itching) at 18 Hours(18 hours post-operatively)
- Visual Analog Scale Pruritus (Itching) at 24 Hours(24 hours post-operatively)
- Visual Analog Patient Satisfaction With Analgesia at 24 Hours(24 hours postoperatively)
研究者
Richard M. Smiley
Professr of Clinical Anesthesiology
Columbia University