Oxytocin Substitution Therapy in Patients With Central Diabetes Insipidus (OxyTUTION)

University Hospital Basel

Status and phase: Enrolling; Phase 2

Conditions: Central Diabetes Insipidus (cDI)

Treatments: Other: Placebo nasal spray; Drug: Intranasal OXT

Study type: Interventional

Funder types: Other

Identifiers

NCT06036004

2023-01010 kt22ChristCrain;

Details and patient eligibility

About

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)

Full 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.

Enrollment: 112 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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112 participants in 2 patient groups, including a placebo group

Study Product Intervention: intranasal OXT

Active Comparator group

Description:

Intranasal OXT spray of 40 IU per ml (Syntocinon®).

Treatment:

Drug: Intranasal OXT

Control Intervention: placebo nasal spray

Placebo Comparator group

Description:

The placebo nasal spray will be identical in volume, labelling, container system, and other features.

Treatment:

Other: Placebo nasal spray