Oxytocin Substitution Therapy in Patients With Central Diabetes Insipidus

NCT06036004 | Recruiting Phase 2

• 1 other identifier: 2023-01010; kt22ChristCrain
• Study Type: interventional
• Target: 112
• Locations: 3 countries
• Sites: 3

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)

Conditions

Central Diabetes Insipidus (cDI)

Keywords

oxytocin (OXT); hypothalamic-pituitary axis; Arginine vasopressin (AVP); OXT deficiency; socio-emotional functioning; intranasal OXT

Outcome Measures

Primary Outcomes (2)

• Change in State-Trait Anxiety Inventory (STAI) questionnaire to assess general anxiety levels

  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.

  Day 0, day 1, day 14, day 28

• Change in EmBody/EmFace to assess recognition of facial and body expressions

  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.

  Day 0, day 1, day 28

Secondary Outcomes (6)

• 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

• 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

Other Outcomes (1)

• Change in Close third-person assessment

  Day 0, day 28

Study Arms (2)

Study Product Intervention: intranasal OXT

ACTIVE COMPARATOR

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

Drug: Intranasal OXT

Control Intervention: placebo nasal spray

PLACEBO COMPARATOR

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

Other: Placebo nasal spray

Interventions

Intranasal OXT 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.

Study Product Intervention: intranasal OXT

Placebo nasal spray 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.

Control Intervention: placebo nasal spray

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (3)

Charité University Medical Center Berlin

Berlin, 10117, Germany

RECRUITING

Erasmus University Medical Center Rotterdam

Rotterdam, 3015, Netherlands

RECRUITING

University Hospital Basel, Department of Endocrinology, Diabetes & Metabolism

Basel, 4031, Switzerland

RECRUITING

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Diabetes Insipidus, Neurogenic; Diabetes Insipidus

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases

Study Officials

• Mirjam Christ-Crain, Prof. Dr. med.

  University Hospital Basel, Department of Endocrinology, Diabetes & Metabolism

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mirjam Christ-Crain, Prof. Dr. med.

CONTACT

+41 61 328 70 80; mirjam.christ-crain@ubs.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study participants, study team (i.e., study nurses, study physicians, study psychologists), and further outcome assessors will be blinded after assignment to interventions.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: double-blind randomised placebo-controlled trial: participants will be randomly assigned 1:1 to receive either treatment with intranasal OXT or intranasal placebo

Study Record Dates

• First Submitted: September 6, 2023
• First Posted: September 13, 2023
• Study Start: January 8, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

DE (1); NL (1); CH (1)