The Effect of Corticotropin Release Hormone on Duodenal Markers and Gastric Sensorimotor Function in Healthy Volunteers
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- The effect of CRH on sensitivity to gastric distention (part 2)
研究概览
简要总结
In the present study, during Part 1, after a baseline gastroduodenoscopy, the investigators will perform a gastroduodenoscopy twice, to take duodenal biopsies before and 2 hours after administration of CRH/placebo. The investigators will measure mucosal integrity and markers of immune activation as outlined in Parts A and B, and will use transmission electron microscopy to evaluate mast cell and eosinophil degranulation. After an interval period of at least 1 week, CRH or placebo will be administrated again in a crossover fashion.
As a complementary study, the investigators will also test the effect of ex vivo mast cell blockade by lodoxamide to evaluate whether mast cells are involved in the hypothesized effect of CRH on duodenal permeability.
In a second part of this study, Part 2, the investigators will perform a gastric barostat, to measure the gastric accommodation and sensitivity to distension, and a carbon-13-octanoic acid breath test to measure the gastric emptying time after administration of CRH/placebo.
Healthy volunteers will have the option to choose to which part of the study (part 1 or 2) they wish to participate. They can also choose to cooperate to both study parts if preferred.
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)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Voluntary written informed consent of the participant has been obtained prior to any screening procedures
- •Women of child-bearing potential agree to apply a highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner. Women of non-childbearing potential may be included if surgically sterile (tubal ligation or hysterectomy) or postmenopausal with at least 2 year without spontaneous menses.
- •Healthy volunteers
- •Subjects aged 18-55 years old (55y included).
- •Male or female subjects.
- •Subjects who are capable to understand the study and the questionnaires, and to comply with the study requirements.
排除标准
- •Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol
- •Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial
- •Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive
- •Presence of a history of gastrointestinal surgery other than appendectomy
- •Presence of organic or functional gastrointestinal disease
- •Presence of gastro-intestinal symptoms
- •Major psychiatric disorder such as major depression
- •Presence of any disease affecting the gastrointestinal tract or hepatobiliary system.
- •History of allergic reaction to CRH
- •BMI equal to 30 mg/kg² or higher.
- •Use of drugs included in this list:
- •Opioids (unless short intake for acute pain and > 1month ago)
- •Amitriptyline or mirtazapine; other antidepressants are allowed if the HV is on a stable dose and the drug is not combined with other antidepressants.
- •Corticosteroids
- •Antihistaminic drugs (last 2 weeks)
- •Proton pump inhibitors (last 2 weeks)
- •Disodiumchromoglycate or other mast cell stabilizers (last 2 weeks)
- •Leukotriene receptor antagonists (last 2 weeks)
- •NSAIDs (last 2 weeks)
- •Antibiotics (last 2 months)
- •Probiotics (last 2 weeks)
- •Other medication: to be discussed with physician
研究组 & 干预措施
Cortisol releasing hormone group
HVs will start with CRH infusion.
干预措施: Corticotropin-release hormone (Drug)
Placebo (sodium choride) group
HVs will start with NaCl 0.9% (placebo) infusion
干预措施: Corticotropin-release hormone (Drug)
结局指标
主要结局
The effect of CRH on sensitivity to gastric distention (part 2)
时间窗: 30 minutes after CRH/placebo
Visceral sensitivity will be measured by barostat. Discomfort threshold will be defined as the first level of pressure and the corresponding volume that provokes discomfort. Pressure thresholds will be expressed both as pressures relative to minimal distending pressure and as absolute pressures.
The effect of corticotrophin release hormone (CRH) on duodenal mast cell count
时间窗: 2 hours after CRH/placebo
Duodenal mast cells (c-kit) will be counted per mm2 via stained duodenal biopsy sections.
次要结局
- The effect of CRH on gastroduodenal symptoms.(Every 15 minutes during CRH/placebo infusion for 4 hours)
- The effect of CRH on duodenal eosinophilia(2 hours after CRH/placebo)
- The effect of CRH on duodenal mucosal permeability(2 hours after CRH/placebo)
- The effect of CRH on gastric emptying time(30 minutes after CRH/placebo)
- The effect of CRH on gastric accommodation(30 minutes after CRH/placebo)
- The effect of CRH on salivary cortisol level(Right before CRH/placebo injection, 15, 30, 60, 120 minutes after injection)