Human Cerebral Blood Flow and Serotonin
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Exercise Performance
研究概览
简要总结
Breathing, blood pressure, and blood flow into the brain are controlled - in part - by small areas in the brainstem; the central chemoreceptors. The mechanisms involved in the transmission of signals through the brainstem and also in controlling brain blood flow past the brainstem both use a molecule called serotonin. Citalopram is a "selective serotonin reuptake inhibitor" (or SSRI) which means it allows serotonin to be released in the brain but stops it from being reabsorbed. SSRIs are often used as antidepressants. This study aims to investigate the influence of an SSRI on the control of brain blood flow.
详细描述
PURPOSE To determine the influence of acute selective serotonin reuptake inhibition (SSRI) on cerebrovascular function in humans
HYPOTHESIS We hypothesize that SSRI will not impact CO2 reactivity (a measure of cerebral vascular function); will reduce neurovascular coupling (a measure of regional cerebral metabolism regulation of the vasculature), and will augment the ventilatory response to CO2 (a measure of brainstem chemosensitivity).
Justification:
There is ample evidence in animal models that the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) is an integral component in neuronal signalling in areas of the brainstem controlling ventilation, and that such 5-HT neurons directly innervate blood vessels and astrocytes (brain cells controlling blood flow) in the brainstem. Brainstem areas, in particular those of the raphe nuclei, containing 5-HT neurons, have been implicated as being actively involved with cerebral microvascular regulation. Extensive preclinical evidence suggests that 5-HT contributes directly to neurogenic control of the vascular beds surrounding raphe nuclei due to neuronal 5-HT release. Furthermore, increases in 5-HT can lead to an uncoupling of CBF and cerebral metabolism.
Increased 5-HT release or availability (e.g., through inhibition of reuptake) leads to a decrease in the relationship between CBF and cerebral metabolism, potentially indicating and impairment in the cerebral vasculature to respond to the needs of brain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
The participant will not know whether they are receiving placebo or SSRI. The primary investigator will also no know if the participant is receiving placebo or SSRI
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •15 healthy participants - mix of male and female - between 18 and 35 years of age will be recruited.
- •The maximum age of 35 was chosen so as to confine this study to "young adults", there is sufficient evidence to suggest that there is great variation of vascular responses to various stimuli across lifetime. As such, including participants from a larger range of ages would inevitably increase the physiological variability of the measures collected and thereby dilute the potential findings. Before assessing the effects of SSRI on CBF and ventilatory responses across the lifetime, we must first assess it in a single age-range cohort, to determine "young healthy normative" data.
排除标准
- •Participants will be excluded from the study if they are:
- •taking any medications,
- •are or have recently (within the previous 6 months) been pregnant (self-reported - or pregnancy test result),
- •currently smoke or smoked within the previous year,
- •have had, or currently have cardiovascular, metabolic, respiratory, or neurological disease,
- •are obese (BMI>30kg/m2),
- •have had any invasive cerebral surgical procedures,
- •have a cardiac pacemaker,
- •we are unable to attain reliable ultrasound images of their neck arteries,
- •currently or within the previous year have been prescribed SSRIs or other serotonergic drugs (tryptophan, triptans, lithium, fentanyl and its analogues, dextromethorphan, tramadol, tapentadol, meperidine, methadone and pentazocine or St. John's Wort),
- •currently or within the previous year been prescribed monoamine oxidase inhibitors (another kind of anti-depressant),
- •have recently (within the previous two weeks) used drugs including lysergic acid diethylamide (LSD), psilocybin (magic mushrooms), cocaine, or 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) (these drugs work via serotonin related mechanisms).
- •Both females and males will be tested. Contraceptive use will be noted but will not be part of any exclusion criteria. Phase of menstrual cycle will be noted but will not be part of any exclusion criteria, though females will be tested within the early follicular phase of menstruation, or the placebo phase of contraceptive use, and tested in the same (self-reported) phase of the next menstrual cycle.
研究组 & 干预措施
Placebo visit
Participants will then undergo pre-intervention testing, with at least 20 minutes of rest between each. Once these tests are complete, the participant will ingest a placebo (sugar pill) that is identical in appearance to the drug condition. Three hours after placebo ingestion all tests will be conducted again. Participants will remain in the lab and will be free to read or work during this resting 3 hour period. This will conclude this experimental visit.
干预措施: Placebo (Other)
结局指标
主要结局
Exercise Performance
时间窗: 3 hours following Citalopram
Maximum volume of oxygen consumed during maximal exercise
Cerebrovascular reactivity to carbon dioxide
时间窗: 3 hours following Citalopram
Cerebral blood flow response to increase in inspired carbon dioxide
Cerebral Blood Flow
时间窗: 3 hours following Citalopram
Blood flow to the brain as measured using duplex ultrasonography
次要结局
- Concentration of Platelet serotonin(3 hours following Citalopram)
研究者
Phil Ainslie
Professor
University of British Columbia