Identification and Clinical Relevance of an Oxytocin Deficient State: a Randomized, Crossover, Placebo-controlled, Proof-of-concept, Physiopathological Study (GLP1 Study)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 52
- 试验地点
- 2
- 主要终点
- Change in oxytocin concentration (pg/mL)
研究概览
简要总结
Oxytocin (OT) is a hypothalamic peptide that enters the peripheral circulation via the posterior pituitary gland. OT plays a key role in regulating appetite, psychopathology, prosocial behavior and sexual function. Hypopituitarism is associated with increased obesity, increased psychopathology, sexual and prosocial dysfunction despite appropriate hormone replacement. A few studies suggest the existence of a possible OT deficient state in hypopituitarism. In animal models, glucagon-like peptide 1 (GLP1) has shown to increase OT release.
This study is designed to evaluate OT values after administration of GLP1 in adults (healthy volunteers and patients with hypopituitarism).
The investigators hypothesize that OT response will be blunted following GLP1 receptor agonist (GLP1-RA) in patients with hypopituitarism compared to healthy controls.
详细描述
This research is focused on two groups of participants: healthy controls (HC) and hypopituitary patients (HYPO) with at least one symptom of hypothalamic damage, presumably at highest risk for OT deficiency.
The aim is to improve knowledge on the physiology and patho-physiology of endogenous OT secretion in hypopituitary patients compared to healthy controls using a randomized, single-blind, crossover assignment (GLP1-RA vs placebo), placebo-control design.
Clinical implications of secretory OT dynamics and release under different stimuli using validated questionnaires to evaluate psychopathology, socio-emotional functioning, disordered eating behavior, impaired quality of life and sexual dysfunction, will be also evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Single (Participant)
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
- •Patients with hypopituitarism (HYPO) (>1 pituitary hormone deficiency) and stable hormone replacement for the prior three months
- •At least one clinical sign of hypothalamic damage
- •Female participants will be done in the early to midfollicular phase
排除标准
- •uncorrected hormone deficiency
- •creatinine >1.5mg/dL
- •alanine aminotransferase (ALT) or aspartate amino transferase (AST) >2.5x upper limit of normal
- •hematocrit less than 30%
- •suicidality or active psychosis
- •participation in a trial with investigational drugs within 30 days
- •using a high glucocorticoid dose
- •Any type of diabetes mellitus
- •Obese patients on GLP1-RA therapies
- •vigorous physical exercise
- •alcohol intake within 24 hours before the study participation
- •evidence of any acute illness or any illness that the Investigator determines could interfere with study participation or safety
- •pregnancy or breastfeeding for last 8 weeks
- •known allergies towards GLP1-RA
- •patients refusing or unable to give written informed consent
- •Additionally for healthy controls: the presence of brain or pituitary tumor, radiation involving the hypothalamus or pituitary, history of hypopituitarism or receiving testosterone or glucocorticoids esters.
结局指标
主要结局
Change in oxytocin concentration (pg/mL)
时间窗: Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection
Change in oxytocin concentration (pg/mL) after administration of 10 µg of GLP1-RA (exenatide) or 0.9% sodium chloride (NaCl)
次要结局
- Quality of life assessment(Baseline)
- Maximal change in oxytocin concentration (pg/mL)(Within the two hours after the injection)
- Mood assessment(Baseline)
- Overall oxytocin secretion (pg/mL)(Within the two hours after the injection)
- Change in glucose concentration (mg/dL)(Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection)
- Change in insulin concentration (pmol/L)(Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection)
- Impulsivity assessment(Baseline)
- Alexithymia assessment(Baseline)