Examining The Effects Of Intravenous Oxytocin Infusion On Peripheral Sensory Afferents Using Microneurography Technique In Healthy Volunteers: A Triple-Blind, Randomized, Placebo-Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Number of nerve fiber discharges with von Frey filament application
研究概览
简要总结
The goal of this clinical trial is to learn if oxytocin reduces pain in a small area of skin after pulses of non-burning heat by changing how nerves in the heated area react to pressing a thin, bendable plastic bristle and a thick, non-bending plastic bristle in adult, healthy participants. The man questions it aims to answer are:
Does oxytocin increase the number of times a fiber which normally responds only to the thin bristle fires (sends a signal) after the heat pulses.
Does oxytocin raise the number of times a fiber which normally responds only to the thick bristle fires (sends a signal) after the heat pulses.
Researchers will compare oxytocin to a placebo (a look-alike substance that contains no drug) to see if oxytocin ABC works to change how nerves react to light touch and painful pressing in an area of sensitized skin.
Participants will:
Receive an intravenous injection of oxytocin or placebo on one occasion On the same day, a needle will be put near nerve fibers to record their firing before and after a few cycles of short heating of the skin.
详细描述
This protocol will utilize a randomized, triple-masked study design to compare intravenous (IV) oxytocin to placebo on peripheral nerve response to acute pain sensitization in healthy volunteers. Equal numbers of adult men and women; ages 18-65 will be recruited. Participants, recruited from the regional community will report to the Linköping University Neurophysiologic Research Laboratory (Linköping, Sweden) for a 2-hour visit to complete eligibility screening, informed consent, pregnancy and drug use laboratory tests, and questionnaires regarding drug and alcohol use, and receive training in the tests to be used on the study day.
On a subsequent study day, participants will come initially to the Linköping University Medical Center where an IV catheter will be inserted and they will receive either IV oxytocin (20 IU) or an equal volume of placebo. Study drug will be randomized and administered in two 30-minute infusions separated by the minutes. Rapid rates of oxytocin infusion can cause acute adverse events in the first minutes of infusion. Although these adverse events rapidly resolve despite continuing the infusion, one event (facial flushing) could negate the blind of study personnel. For that reason, the first infusion will be given at 2 rates, a very slow rate for the first 5 minutes and a greater rate for the remaining 25 minutes. This has been demonstrated to reduce the incidence of facial flushing with oxytocin to a rate similar to placebo. Participants will be continuously monitored for vital signs and intermittently queried for any subjective sensations or adverse events during infusion.
After study drug infusion is complete, the IV catheter will be removed and the participant accompanied to the Linköping University Neurophysiologic Research Laboratory, adjacent to the Medical Center, where they will complete psychologic questionnaires and cognitive tests and undergo sensory testing of the skin on the arm of brushing using a computer controlled, robotic system. Then, a 200 micrometer tungsten electrode will be inserted in the radial or peroneal nerve under real-time ultrasound guidance and manipulated until a single nerve fiber and its area of skin innervation (receptive field) are identified. The nerve fiber will be categorized by its speed of conduction and firing pattern to a variety of non-noxious and noxious sensory stimuli to the receptive field. A temperature controlled thermode will be placed on the skin adjacent to and overlapping with the receptive field and acute inflammation induced by 10-second cycles of heating the probe to 50°C with 10 seconds at a non-noxious temperature (30°C) between each heat pulse for a total of 2 minutes. The response of the nerve fiber to noxious and non-noxious stimuli will be repeated.
The primary analysis will compare fiber firing in response to a fixed intensity punctate stimulus in the fiber's receptive field between oxytocin and placebo and will be performed separately on touch-sensitive fibers (fast conducting, low threshold mechanoreceptors (A-LTMRs)) and pain-sensitive fibers (fast conducting, low threshold mechanoreceptors (A-HTMRs)).
Based on numerous studies performed in rodents at Wake Forest University School of Medicine, we hypothesize that acute heat-induced inflammation will render A-LTMRs less responsive to a touch punctate stimulus and A-HTMRs more responsive to a noxious punctate stimulus and that both of these effects will be reduced by at least 50% in participants who receive IV oxytocin. If such results are obtained, they will challenge the existing paradigm that reduction in pain threshold (allodynia) after sensitization from peripheral injury is driven by increased A-LTMR input and support further exploration for the mechanisms by which oxytocin returns changes in touch and pain fibers towards normal to treat pain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The Linkoeping University (Linkoeping, Sweden) research pharmacy will prepare solutions and dispense them on the day of each study using a randomization stratified by sex that will be concealed until the end of the clinical trial.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •In good health as determined by the Principal Investigator (PI) or co-investigators based on prior medical history, current psychiatric assessment, and clinical assessment of lab tests.
- •Female participants of child-bearing potential including those < 1 year post-menopausal, must be practicing highly effective methods of birth control such as hormonal methods (e.g., combined oral, implantable, injectable, or transdermal contraceptives), double barrier methods (e.g., condoms, sponge, diaphragm, or vaginal ring plus spermicidal jellies or cream), or abstinence from heterosexual intercourse for a minimum of 1 full cycle before study drug administration.
- •Normal blood pressure (systolic 90-140 mmHg; diastolic 50-90 mmHg) resting heart rate 45-100 beats per minute) without medication.
- •Proficient in Swedish or English
排除标准
- •Hypersensitivity, allergy, or a history of significant reaction to any ingredients of the active drug (Oxytocin Grindeks® 8.7 microgram/ml solution) or the placebo (Sodium Chloride , ATC code: V07AB).
- •Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the PI, would place the participant at increased risk (active gynecologic disease in which increased uterine tone would be detrimental e.g., uterine fibroids with ongoing bleeding), compromise the participant's compliance with study procedures, or compromise the quality of the data.
- •Women who are pregnant (positive result for urine pregnancy test at screening visit), women who are currently nursing or lactating, women that have been pregnant within 2 years.
- •Body Mass Index (BMI) > 30
- •Participants with neuropathy, chronic pain, diabetes mellitus, or taking benzodiazepines or pain medications on a daily basis.
- •Participants with current or history of ventricular tachycardia, atrial fibrillation or prolonged QT interval.
- •Participants with past or current history of hyponatremia or at risk for hyponatremia; anyone taking thiazide diuretics, loop diuretics, combination diuretics, lithium, carbamazepine, enalapril, ramipril, celecoxib, temazepam, gliclazide, glimepiride, glibenclamide, glipizide, omeprazole, pantoprazole, desmopressin, antidepressants (SSRI's or MAOI), or the recreational drug ecstasy.
- •Participants with a known latex allergy.
- •Participants with substances use disorders or any other psychiatric disorder(s).
- •Participant with high risk of fainting episodes.
研究组 & 干预措施
Intravenous Oxytocin
Oxytocin, 10 International Units (IU) will be administered by IV infusion over 30 minutes and, 30 minutes later, a second 10 IU will be administered over 30 min, for a total dose of 20 IU. The first infusion will be at a rate of 0.125 IU/min for the first 5 min, then at 0.375 IU/min for the remaining 25 min. The second 30-min infusion will be at a fixed rate of 0.333 IU/min.
干预措施: Intravenous Oxytocin (Drug)
Intravenous Placebo
Saline will be administered as two 30-min IV infusions separated by 30-min, using the same volume of infusion solution and rates of administration as in the intravenous oxytocin intervention.
干预措施: Intravenous Placebo (Drug)
结局指标
主要结局
Number of nerve fiber discharges with von Frey filament application
时间窗: 2-8 hours after start of the first IV infusion
The number of nerve fiber discharges in response to a 5 second application of a 20 mN force von Frey filament and to a 1000 mN force von Frey filament to the area of skin responding to sensory stimulation. These are measured twice, once before and once after skin inflammation induced by heat pulses.
次要结局
- Verbal pain intensity score with von Frey filament application(2-8 hours after start of the first IV infusion)
- Pattern of nerve fiber discharges with von Frey filament application(2-8 hours after start of the first IV infusion)
- Number of nerve fiber burst discharges with tuning fork application(2-8 hours after start of the first IV infusion)
- Number of nerve fiber discharges with warming and cooling(2-8 hours after start of the first IV infusion)
- Number of nerve fiber discharges with soft brushing(2-8 hours after start of the first IV infusion)
- Number of nerve fiber discharges with von Frey filament application: stimulus response relationship(2-8 hours after start of the first IV infusion)
- Inflammation response to skin heating(2-8 hours after start of the first IV infusion)