Clinical trial NCT06036004: Oxytocin Substitution Therapy in Patients With Central Diabetes Insipidus
Official title: Oxytocin Substitution Therapy in Patients With Central Diabetes Insipidus: a Double-blind Randomised Placebo-controlled Trial: the OxyTUTION Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Central Diabetes Insipidus (cDI)
Keywords: oxytocin (OXT)
hypothalamic-pituitary axis
Arginine vasopressin (AVP)
OXT deficiency
socio-emotional functioning
intranasal OXT
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2023-09-13
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double-blind randomised placebo-controlled trial: participants will be randomly assigned 1:1 to receive either treatment with intranasal OXT or intranasal placebo
Primary purpose: TREATMENT

Brief summary: 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)

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Regular use (\> 3 times per week) of sympathomimetic drugs (e.g., bronchodilators)

Primary outcomes:
measure: Change in State-Trait Anxiety Inventory (STAI) questionnaire to assess general anxiety levels
timeFrame: Day 0, day 1, day 14, day 28
measure: Change in EmBody/EmFace to assess recognition of facial and body expressions
timeFrame: Day 0, day 1, day 28
Secondary outcomes:
measure: Change in Facial emotion recognition task (FERT) to assess emotion recognition and empathy
timeFrame: Day 0, day 28
measure: Change in Multifaceted Empathy Test (MET) to assess the cognitive and emotional aspects of empathy
timeFrame: Day 0, day 1, day 28
measure: Change in Hamilton Anxiety Rating Scale (HAM) to assess the severity of anxiety symptoms
timeFrame: Day 0, day 28
measure: Change in Toronto Alexithymia Scale 20 (TAS-20) to assess emotions experienced by oneself or others
timeFrame: Day 0, day 28
measure: Change in Autism-Spectrum Quotient Test (AQ) to assess the expression of ASD traits in an individual by his or her subjective self-assessment
timeFrame: Day 0, day 28
measure: Change in Beck's Depression Inventory II (BDI-II) to assess depression
timeFrame: Day 0, day 28
Other outcomes:
measure: Change in Close third-person assessment
timeFrame: Day 0, day 28
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center Rotterdam
city: Basel
country: Switzerland
facility: University Hospital Basel, Department of Endocrinology, Diabetes & Metabolism
Study officials:
affiliation: University Hospital Basel, Department of Endocrinology, Diabetes & Metabolism
name: Mirjam Christ-Crain, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: