Oxytocin Substitution Therapy in Patients With Central Diabetes Insipidus

NCT ID: NCT06036004

Last Updated: 2026-01-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-08
• Study Completion Date: 2026-10-31

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.

Conditions

Central Diabetes Insipidus (cDI)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Study Product Intervention: intranasal OXT

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

Group Type: ACTIVE_COMPARATOR

Intranasal OXT

Intervention Type: DRUG

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.

Control Intervention: placebo nasal spray

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

Group Type: PLACEBO_COMPARATOR

Placebo nasal spray

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mirjam Christ-Crain, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Basel, Department of Endocrinology, Diabetes & Metabolism

Locations

Erasmus University Medical Center Rotterdam

Rotterdam, , Netherlands

Site Status: NOT_YET_RECRUITING

University Hospital Basel, Department of Endocrinology, Diabetes & Metabolism

Basel, , Switzerland

Site Status: RECRUITING

Countries

Netherlands; Switzerland

Central Contacts

Mirjam Christ-Crain, Prof. Dr. med.

Role: CONTACT

mirjam.christ-crain@ubs.ch

+41 61 328 70 80

Facility Contacts

Julie Refardt, MD PhD

Role: primary

j.refardt@erasmusmc.nl

+31627112079

Mirjam Christ-Crain, Prof. Dr. med.

Role: primary

mirjam.christ-crain@ubs.ch

+41 61 328 70 80

Other Identifiers

2023-01010; kt22ChristCrain

Identifier Type: -

Identifier Source: org_study_id