Oxytocin Substitution Therapy in Patients With Central Diabetes Insipidus

Официальное название

Oxytocin Substitution Therapy in Patients With AVP Deficiency (Central Diabetes Insipidus)

Обзор

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)

Подробное описание

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.

Optional Social-stress sub-study: The three main components are an anticipation phase, a 5-minute interview, and a surprise mental arithmetic task. Acute stress is measured by cortisol increase.

Вмешательства

• Препарат Intranasal OXT
  Syntocinon® contains the synthesized peptide OXT in a solution formulated to promote absorption through the nasal mucosa. Additional ingredients are E216 (propyl-4-hydroxybenzoate), E218 (methyl-4-hydroxybenzoate), and chlorobutanol hemihydrate. One bottle contains 5 ml, i.e., 200 IU of OXT in total. Each 0.1 ml nasal insulation delivers 4 IU of oxytocin. OXT (24 IU twice daily) is given for 28 (± 2) days of treatment.
• Другое Placebo nasal spray
  The placebo will contain no OXT but, otherwise, be identical to the intranasal OXT product with respect to the other ingredients. Placebo is given twice daily for 28 (± 2) days of treatment.

Первичные конечные точки

• Change in State-Trait Anxiety Inventory (STAI) questionnaire to assess general anxiety levels [Срок оценки: Day 0, day 1, day 14, day 28]
• Change in EmBody/EmFace to assess recognition of facial and body expressions [Срок оценки: Day 0, day 1, day 28]

Вторичные конечные точки (6)

• Change in Facial emotion recognition task (FERT) to assess emotion recognition and empathy [Срок оценки: Day 0, day 28]
• Change in Multifaceted Empathy Test (MET) to assess the cognitive and emotional aspects of empathy [Срок оценки: Day 0, day 1, day 28]
• Change in Hamilton Anxiety Rating Scale (HAM) to assess the severity of anxiety symptoms [Срок оценки: Day 0, day 28]
• Change in Toronto Alexithymia Scale 20 (TAS-20) to assess emotions experienced by oneself or others [Срок оценки: Day 0, day 28]
• Change in Autism-Spectrum Quotient Test (AQ) to assess the expression of ASD traits in an individual by his or her subjective self-assessment [Срок оценки: Day 0, day 28]
• Change in Beck's Depression Inventory II (BDI-II) to assess depression [Срок оценки: Day 0, day 28]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Германия · 1 центр

• Charité University Medical Center Berlin — Berlin

Нидерланды · 1 центр

• Erasmus University Medical Center Rotterdam — Rotterdam

Швейцария · 1 центр

• University Hospital Basel, Department of Endocrinology, Diabetes & Metabolism — Basel

Публикации

• Atila C, Leibnitz S, Nikaj A, Liechti ME, De Quervain D, Christ-Crain M; OxyTUTION Study Group. Oxytocin substitution therapy in patients with AVP deficiency (central diabetes insipidus): study protocol of a double-blind, randomised placebo-controlled trial. BMJ Open. 2026 May 4;16(5):e109940. doi: 10.1136/bmjopen-2025-109940. PMID 42082227

Идентификаторы

NCT: NCT06036004 · 2023-01010; kt22ChristCrain

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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