Evaluation of Intranasal Oxytocin in Central Diabetes Insipidus: A Double-Blind, Randomized, Placebo-Controlled Trial

The primary objective of this study is to evaluate the effect of intranasal **oxytocin** (OXT) at a dosage of 24 IU administered twice daily, compared to a placebo, over a period of 28 days (±2 days) in patients with central diabetes insipidus. The study aims to assess changes in anxiety levels using the State-Trait Anxiety Inventory (Trait-Anxiety Scale, STAI-T) and changes in the correct recognition of facial and body expressions through the EmBody/EmFace Task. This is clinically relevant as it explores the potential therapeutic benefits of OXT in managing anxiety and enhancing social cognition in this patient population.

Secondary objectives include:

• Evaluating emotion recognition and empathy.
• Assessing hormonal and subjective responses to psychological stress.
• Investigating amygdala and subjective responses in functional MRI scans.
• Measuring other psychological parameters.
• Analyzing metabolic parameters.
• Conducting objective assessments by a third party.
• Ensuring safety measures are in place.

The clinical trial involves a total of **62 participants** diagnosed with **central diabetes insipidus**. The study population includes both male and female adults, with an age range corresponding to categories 3 and 4, which typically represent individuals aged 18 to 64 years. Participants were selected based on a confirmed diagnosis of central diabetes insipidus and heightened self-reported anxiety or alexithymia levels. All participants are on stable hormone replacement therapy with desmopressin, and if necessary, additional substitution therapies for anterior pituitary deficiencies. The trial does not include a vulnerable population. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria. The study aims to assess the effect of intranasal oxytocin on anxiety levels and the recognition of facial and body expressions over a 28-day period.

The clinical trial is designed to evaluate the efficacy of **oxytocin** administered via nasal spray in patients with central diabetes insipidus. This study is a **randomized**, **double-blind**, **placebo-controlled** trial, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, thus minimizing bias. The trial is set to last for a total of 28 days, with a permissible variation of plus or minus 2 days. Participants will be randomly assigned to receive either the oxytocin nasal spray or a placebo nasal spray, which is identical in appearance but contains 0.9% sodium chloride without oxytocin.

The trial will commence with an inclusion (screening) visit, where potential participants will be assessed against the inclusion criteria, which include a confirmed diagnosis of central diabetes insipidus and heightened self-reported anxiety or alexithymia levels. Following successful screening, participants will be enrolled in the study. The primary objective is to assess changes in anxiety levels and the correct recognition of facial and body expressions, using the State-Trait Anxiety Inventory and the EmBody/EmFace Task, respectively. Secondary endpoints include emotion recognition, empathy, hormonal responses to stress, and various psychological and metabolic outcomes.

Participants will be required to attend several study visits throughout the trial duration. These visits will include baseline assessments, mid-study evaluations, and an end-of-study visit to collect data on the primary and secondary endpoints. The expected length of participant involvement is approximately 4 weeks. Conditions that may lead to early termination from the study include adverse reactions to the treatment, non-compliance with the study protocol, or withdrawal of consent by the participant.

The trial is anticipated to start recruiting participants on November 1, 2024, and is expected to conclude by September 30, 2026. The study is conducted under the guidelines of a Phase 4 trial, focusing on a new treatment indication for oxytocin, which is already approved for other uses in certain regions. The trial aims to provide valuable insights into the potential therapeutic benefits of oxytocin for patients with central diabetes insipidus.

The clinical trial involves the administration of **oxytocin** as the experimental medication. Oxytocin is provided in the form of a nasal spray, with the pharmaceutical form designated as PHF00231MIG. The active substance, oxytocin, is a synthesized peptide with the ATC code H01BB02. The nasal spray is administered intranasally at a dosage of 24 international units (IU) twice daily, resulting in a maximum daily dose of 48 IU. The total maximum dose over the treatment period is 80 IU. The treatment duration is set for 28 days, with a permissible variation of plus or minus 2 days. The original label of the primary packaging is replaced with a clinical trial medication label to ensure proper identification and compliance with trial protocols.

The comparator treatment in this study is a placebo nasal spray. The placebo is designed to be identical in volume and labeling to the oxytocin nasal spray, although it differs in the container system and other features. The placebo contains 0.9% sodium chloride and does not include oxytocin. The placebo is administered following the same route and frequency as the experimental medication, ensuring a double-blind study design. This approach allows for the assessment of the effects of oxytocin substitution therapy in patients with central diabetes insipidus, specifically focusing on changes in anxiety levels and the recognition of facial and body expressions.

Efficacy in the clinical trial titled "Oxytocin substitution therapy in patients with AVP deficiency (central diabetes insipidus): a double-blind randomised placebo-controlled trial - the OxyTUTION trial" will be assessed through primary and secondary endpoints. The primary endpoints include changes in anxiety levels and the correct recognition of facial and body expressions after 28 days of treatment. These will be measured using the State-Trait Anxiety Inventory (Trait-Anxiety Scale, STAI-T) and the EmBody/EmFace Task. The STAI-T consists of 20 items, each scored from 1 to 4 points, while the EmBody/EmFace Task includes 84 items scored as correct or incorrect.

Secondary endpoints will evaluate additional parameters such as emotion recognition and empathy, hormonal and subjective responses to psychological stress, amygdala and subjective responses in functional MRI scans, further psychological outcomes, metabolic outcomes, objective assessments by a close third person, and safety outcomes. The trial will involve the administration of **oxytocin** via nasal spray, with a dosage of 24 IU twice daily, compared to a placebo containing 0.9% sodium chloride. The efficacy assessments will be conducted over a treatment period of 28 days, with the primary focus on the hypothesized decrease in anxiety and/or increase in correct classification of facial and body expressions in the oxytocin group compared to the placebo group.