Oxytocin Substitution Therapy in Patients With AVP Deficiency (Central Diabetes Insipidus)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 112
- 试验地点
- 3
- 主要终点
- Change in State-Trait Anxiety Inventory (STAI) questionnaire to assess general anxiety levels
研究概览
简要总结
This randomized, placebo-controlled, double-blind trial aims to investigate intranasal OXT as a novel therapeutical option in central diabetes insipidus (cDI) to improve psychological symptoms and socio-emotional functioning.
Optionally, patients can present for additional assessments in sub-studies:
- fMRI sub-study at day 14 (± 2 days) (one additional visit)
- Social-stress sub-study at day 14 (± 2 days) (one additional visit)
详细描述
Arginine vasopressin (AVP) and oxytocin (OXT) are hormones released into circulation from the posterior pituitary. While AVP acts mainly in the kidneys and causes reuptake of free water, OXT is well-known for its key role in the regulation of complex social-emotional functioning including attachment and pair bonding, fear possessing, emotion recognition, and empathy.
Disruption of the hypothalamic-pituitary axis can cause AVP deficiency
- known as central diabetes insipidus (cDI) - characterized by polyuria and polydipsia. Once diagnosed, desmopressin (an AVP receptor analogue) can be effectively used to treat diabetes insipidus. However, despite treatment with desmopressin, patients often report residual psychological symptoms, particularly heightened anxiety levels, depressed mood, impairment in social interactions, leading to an overall reduced quality of life.
Due to the anatomical proximity, local disruptions of the AVP system could also disturb the OXT system leading to an additional OXT deficiency. The additional OXT deficiency could explain (at least partially) the residual psychological deficits in patients with cDI. OXT replacement therapy to improve psychological symptoms would have great clinical implications. This randomized, placebo-controlled, double-blind trial aims to investigate intranasal OXT as a novel therapeutical option in cDI to improve psychological symptoms and socio-emotional functioning.
Optional fMRI sub-study: Participants will undergo a structural sequence to investigate grey and white matter anatomy (T1- weighted). Functional neuronal responses will be assessed through the surrogate of blood oxygenated level dependent (BOLD) signal, an indirect measure of neural activity. Three functional sequences (echo planar imaging, EPI) will investigate group differences in various aspects of brain activity: a resting state sequence and the EFMT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Study participants, study team (i.e., study nurses, study physicians, study psychologists), and further outcome assessors will be blinded after assignment to interventions.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients with a confirmed diagnosis of central diabetes insipidus based on accepted criteria
- •Heightened anxiety levels (STAI - Trait subscale ≥ 39 score points) or alexithymia levels (impaired ability to identify and describe feelings; TAS-20 total ≥ 52 score points)
- •Stable hormone replacement therapy for at least three months with desmopressin and, in case of additional anterior pituitary deficiencies, with the respective substitution therapies.
排除标准
- •Participation in a trial with investigational drugs within 30 days
- •Active substance use disorder within the last six months
- •Consumption of alcoholic beverages >15 drinks/week
- •Current or previous psychotic disorder (e.g., schizophrenia spectrum disorder)
- •Pregnancy and breastfeeding within the last eight weeks
- •Unwilling to use a medically acceptable form of contraception throughout the study period (female of childbearing potential only)
- •Prolonged QTc-time >470 ms assessed with a 12-lead electrocardiogram.
研究组 & 干预措施
Study Product Intervention: intranasal OXT
Intranasal OXT spray of 40 IU per ml (Syntocinon®).
干预措施: Intranasal OXT (Drug)
Control Intervention: placebo nasal spray
The placebo nasal spray will be identical in volume, labelling, container system, and other features.
干预措施: Placebo nasal spray (Other)
结局指标
主要结局
Change in State-Trait Anxiety Inventory (STAI) questionnaire to assess general anxiety levels
时间窗: Day 0, day 1, day 14, day 28
Questionnaire with scores ranging from 1 ("almost never") to 4 ("almost always"). The STAI has two sub-scales, the State-Anxiety Scale (STAI-S; 20 items) and the Trait-Anxiety Scale (STAI-T; 20 items). The STAI-S evaluates the current state of anxiety, asking how respondents feel "right now," using items that measure subjective feelings of apprehension, tension, nervousness, worry, and activation/arousal of the autonomic nervous system. The STAI-T evaluates relatively stable aspects of "anxiety proneness," including general states of calmness, confidence, and security. The total scores range from 20 to 80, with higher scores indicating more pronounced anxiety. A score above 39/80 indicates clinically significant anxiety symptoms.
Change in EmBody/EmFace to assess recognition of facial and body expressions
时间窗: Day 0, day 1, day 28
The EmBody and EmFace subtasks comprise each of 42 stimuli showing body or facial expressions of angry, happy, or neutral affect. Stimuli last 1.5 seconds at 24 frames per second and are geometrically and optically standardised to prevent biases induced by ethnic cues. Each trial consists of one point-light display (PLD), followed by a response window during which participants are asked to indicate via mouse input which emotion they believe was portrayed in the PLD in a three-option forced-choice format (angry-neutral-happy). The total correct classification scores range from 0 to 42 (for each sub-task), with higher scores indicating more correct recognition of facial \& body expressions.
次要结局
- Change in Autism-Spectrum Quotient Test (AQ) to assess the expression of ASD traits in an individual by his or her subjective self-assessment(Day 0, day 28)
- Change in Beck's Depression Inventory II (BDI-II) to assess depression(Day 0, day 28)
- Change in Facial emotion recognition task (FERT) to assess emotion recognition and empathy(Day 0, day 28)
- Change in Multifaceted Empathy Test (MET) to assess the cognitive and emotional aspects of empathy(Day 0, day 1, day 28)
- Change in Hamilton Anxiety Rating Scale (HAM) to assess the severity of anxiety symptoms(Day 0, day 28)
- Change in Toronto Alexithymia Scale 20 (TAS-20) to assess emotions experienced by oneself or others(Day 0, day 28)