The Role of Orexin in Human Panic Disorder
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Change in Orexin Levels (Blood) +1 Minute
研究概览
简要总结
The purpose of this study is to provide some information (pilot data) about whether the study drug, suvorexant, (1) affects levels of orexin in people with panic disorder, and (2) is associated with decreased panic symptoms in response to a carbon dioxide (CO2) challenge.
详细描述
Orexins
Hypocretins (orexins), a more recently identified class of pro-arousal neuropeptides, are synthesized by neurons in the lateral and posterior hypothalamus The main described orexins, orexin A (ORX A) and orexin B (ORX B), are both cleaved from a common precursor peptide, prepro-orexin. Orexin A, a 33 amino-acid residue peptide, appears to be conserved across many mammalian species. Orexin B contains 28 amino acids. Orexins promote a variety of behaviors including alertness, vigilance, locomotion, fight-flight responses, and feeding. The physiological effects of the orexins are mediated via 2 G-protein coupled receptors, ORX1 and ORX2. Orexin A binds with greater affinity to the ORX1 receptor, while orexin A and B bind with similar affinity to the ORX2 receptor.
Orexins and Animal Fear Models
Orexins have been implicated in anxiogenesis in some animal fear models. For example, central (icv) injection of orexin A in mice induced anxiety-like responses in the light-dark exploration test and elevated plus maze.
Using an established, γ-aminobutyric acid (GABA)-deficit, rodent model of panic-vulnerability, the investigators' Indiana University preclinical anxiety collaborators provoked a panic-like response in rodents with an anxiogenic sodium lactate (NaLac) infusion, which response was blunted following either site-specific orexin (ORX) gene silencing or systemic pretreatment with an ORX1 antagonist.
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)
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
- 否
入选标准
- •They must be in stable physical health as determined by a medical evaluation, including physical examination, electrocardiogram, laboratory findings (comprehensive metabolic panel, complete blood count [CBC], free T4, urine pregnancy test, urinalysis), urine toxicology screen, and a negative urine pregnancy test in women of child-bearing potential.
- •They must satisfy the new clinical criteria in the Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) for a current principal diagnosis of PD as confirmed by a semi-structured, diagnostic interview, the Mini International Neuropsychiatric Interview (MINI), administered by the PI.
- •Since clinical depression (MDD) is associated with CSF ORX abnormalities, only patients with a current PD without MDD will be enrolled. They will also be required to have a current Montgomery-Asberg Depression Rating Scale (MADRS) total score <
- •They will be off all regular psychiatric medications and avoid drinking grapefruit juice for at least 2 weeks prior to the 35% CO2 test.
- •They must not be pregnant or breastfeeding a baby; and women of childbearing potential must be using birth control while on this study.
排除标准
- •any history of a psychotic disorder, bipolar disorder, MDD, depression not otherwise specified (NOS), obsessive compulsive disorder, an eating disorder, post-traumatic stress disorder, or generalized anxiety disorder
- •medical conditions for which suvorexant could be contraindicated, such as narcolepsy
- •any other sleep disorder
- •a substance use disorder, as defined by the DSM-5, within 6 months of the screening visit
- •ongoing use of psychiatric medications in the 2 weeks prior to the 35% CO2 test
- •current use of certain drugs, including
- •strong cytochrome P450 3A (CYP3A) inhibitors (such as ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin, and conivaptan);
- •moderate CYP3A inhibitors (such as amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil);
- •strong CYP3A inducers (such as rifampin, carbamazepine and phenytoin);
- •history of any neurological disorder affecting the CNS
- •history of uncontrolled or serious medical illness
- •a history of hypersensitivity or allergy to suvorexant
- •pregnancy or lactation status, or unwillingness to use birth control while on this study, for women of child-bearing potential
- •compromised lung function (e.g., chronic obstructive pulmonary disease [COPD], emphysema, idiopathic pulmonary fibrosis, lung cancer)
- •inability to fast the required amount of time prior to study visit 2
- •a positive test for cannabinoids, opiates, benzodiazepines, amphetamines, cocaine and metabolites
- •out-of-range lab values
- •an abnormal EKG
- •a score > 12 on the Montgomery-Asberg Depression Rating Scale (MADRS)
- •inability or unwillingness to avoid drinking grapefruit juice for two weeks prior to the 35% CO2 challenge test
- •a history of sudden onset of muscle weakness (cataplexy)
研究组 & 干预措施
Suvorexant Group
In this arm, subjects will receive 10 mg suvorexant 2 hours before a one-minute 35% CO2 challenge.
干预措施: suvorexant (Drug)
Placebo Group
In this arm, subjects will receive a placebo, compounded to look identical to the study drug, 2 hours before a one-minute 35% CO2 challenge.
干预措施: placebo (Drug)
结局指标
主要结局
Change in Orexin Levels (Blood) +1 Minute
时间窗: Baseline and +1 minute post-CO2 challenge
Change in orexin levels from baseline to +1 min post-CO2 challenge
Change in Orexin Levels (Blood) +5 Minutes
时间窗: Baseline and +5 minutes post-CO2 challenge
Change in orexin levels from baseline to +5 min post-CO2 challenge
Change in Orexin Levels (Blood) +15 Minutes
时间窗: Baseline and +15 minutes post-CO2 challenge
Change in orexin levels from baseline to +15 min post-CO2 challenge
Change in Orexin Levels (Blood) +60 Minutes
时间窗: Baseline and +60 minutes post-CO2 challenge
Change in orexin levels from baseline to +60 min post-CO2 challenge
次要结局
未报告次要终点