Heritability of Opioid Effects: A Twin Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 242
- 试验地点
- 1
- 主要终点
- Heat Pain Threshold
研究概览
简要总结
Proposed twin study will test to what degree inter-individual differences in pain sensitivity and amount of pain relief in response to opioid therapy are inherited or alternatively, are due to environmental factors. This knowledge is important to guide future studies trying to explain such inter-individual differences. For example, finding that differences are largely due to environmental factors would discourage genomic studies and emphasize epidemiological studies.
详细描述
The principal hypothesis to be evaluated is that the degree of analgesia provided by opioids in humans displays substantial familial aggregation, and is, in fact, heritable. These studies will use a classical twin paradigm to determine the role of genetics and the environment in influencing analgesia and a range of other opioid effects.
Specific Aims: (1) Determine the degree to which opioid analgesic responses show familial aggregation and make preliminary estimates of heritability using both a heat and cold pressor pain model, and (2) determine the degree to which non-analgesic opioid responses show familial aggregation and make preliminary estimates of heritability. Side effects such as sedation, nausea, respiratory depression, and pruritus, as well as the positive affective response, a measure of abuse potential, will be monitored. Monozygotic (MZ) and dizygotic (DZ) twin pairs (125 total pairs) will be tested under controlled pain laboratory conditions for their responses to opioid infusion using the complementary pain models while monitoring side effects and additional psychometric indices of mood, sleep, and abuse potential. The selected models provide unique mechanistic information because they involve different peripheral and/or central pain pathways. DNA samples will be collected for zygosity testing and banked for future studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Monozygotic or dizygotic twins ages 18-70
排除标准
- •(1) Clinically relevant systemic diseases such as psychiatric, neurological, and dermatological conditions interfering with the collection and interpretation of study data (2) History of addiction (3) Allergy to study medication (4) Chronic intake of medication potentially interfering with pain processing (except oral contraceptives) (5) Intake of over-the-counter analgesics within the two days prior to study (6) Reynaud's disease (7) Pregnancy (8) Participation in other study within last 30 days (9) Personnel with direct access to addicting drugs
研究组 & 干预措施
Saline placebo infusion
Subjects will receive an intravenous infusion of normal saline.
干预措施: Saline placebo infusion (Other)
Alfentanil infusion
Subjects will receive an intravenous infusion of alfentanil.
干预措施: Alfentanil (Drug)
结局指标
主要结局
Heat Pain Threshold
时间窗: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
Degrees Centigrade Heat pain was induced with a thermal sensory analyzer (TSA-II, Medoc Advanced Medical Systems, Durham, North Carolina). A thermode was placed in contact with skin at the volar forearm. Starting at a comfortable temperature, the thermode temperature was increased at a measured rate. Study participants pushed a button of a hand-held device at the onset of pain at which point the thermode immediately reduced the temperature.
Cold Pain Threshold
时间窗: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
Time in seconds Sensitivity to cold-pressor pain was tested by asking subjects to immerse their hand up to the wrist in ice water (1-2 C) continuously re-circulated within a 12-L container with the palm of the hand in full contact with the bottom of the container.They were asked to indicate the onset of pain - reported as pain threshold.
Cold Pain Tolerance
时间窗: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
Time in seconds Sensitivity to cold-pressor pain was tested by asking subjects to immerse their hand up to the wrist in ice water (1-2 C) continuously re-circulated within a 12-L container with the palm of the hand in full contact with the bottom of the container.They were asked to remove their hand from the water bath when it was no longer tolerable - reported as pain tolerance.
Respiratory Rate
时间窗: Measured throughout the study session ~ 5 hours
Breaths per minute counted by direct observation and additionally recorded / external electronic monitoring.
Transcutaneous Partial Pressure of Carbon Dioxide
时间窗: Measured continuously throughout the study session ~ 5 hours
Partial pressure of transcutaneous carbon dioxide (CO2) was measured with aid of a pO2/pCO2-electrode (Perimed Inc., North Royalton, OH) mounted to the anterior chest wall.
次要结局
- Sedation(The trail making test was performed at training prior to study procedures, at baseline, and during each of the infusions.)
- Average Pruritis(At the end of each infusion stage. 2 times total.)
- Maximum Pruritis(At the end of each infusion stage. 2 times total.)
- Average Nausea(At the end of each infusion stage. 2 times total.)
- Average Drug Liking(At the end of each infusion stage. 2 times total.)
- Maximum Drug Disliking(At the end of each infusion stage. 2 times total.)
- Maximum Drug Liking(At the end of each infusion stage. 2 times total.)
- Maximum Nausea(At the end of each infusion stage. 2 times total.)
- Sedation by Patient Report(At the end of each infusion stage. 2 times total.)
研究者
Martin Angst
Professor of Anesthesia
Stanford University