Effect of Intranasal Oxytocin on Emotion Recognition and Acute Psycho-Social Stress-induced Cortisol Increase in Patients With Central Diabetes Insipidus (Arginine Vasopressin Deficiency) and Healthy Controls - the OxyMOTION-Study
Overview
- Phase
- Phase 2
- Intervention
- Oxytocin nasal spray
- Conditions
- Arginine Vasopressin Deficiency
- Sponsor
- University Hospital, Basel, Switzerland
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Effect of oxytocin compared to placebo in patients with AVP deficiency compared to healthy controls on recognition of facial emotions/body expression
- Status
- Recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
This study aims to investigate the potential beneficial effects of intranasal oxytocin compared to placebo on emotion recognition and acute psychosocial stress in patients with arginine vasopressin deficiency compared to matched healthy controls.
Detailed Description
Arginine vasopressin (AVP) and oxytocin are both nine-amino acid neuropeptides produced in the hypothalamus and are released into circulation from axon terminals projecting to the posterior pituitary. Disruption of the hypothalamic-pituitary axis due to inflammation, tumours, or head trauma may cause AVP deficiency, formerly known as central diabetes insipidus, a condition characterised by polyuria and polydipsia. Once diagnosed with AVP deficiency, desmopressin (AVP receptor 2 analogue) is prescribed to overcome polyuria and polydipsia symptoms. However, despite adequate treatment with desmopressin, patients often report residual psychological symptoms such as heightened anxiety, impairment in identifying and expressing emotions, lower levels of empathy, and increased stress-related behaviour. Oxytocin regulates complex socio-emotional functioning, including attachment and pair bonding, fear extinction, emotion recognition, and empathy. In line with this, oxytocin acts as a stress-buffering hormone as it reduces cortisol in response to stress and has anxiolytic effects. In addition to its release from axonal terminals, there is dendritic release of oxytocin into the brain, including key regions engaged in social-emotional behaviour such as the amygdala, hippocampus, insula. Specifically, it has been supposed that the prosocial effect of oxytocin might be secondary to an anxiolytic effect that involves modulation of amygdala responsivity and by improving emotion recognition. Due to the anatomical proximity, disruption of the AVP system leading to AVP deficiency could also disturb the oxytocin system leading to an additional oxytocin deficiency. Therefore, the psychopathological findings in patients may be caused by an additional oxytocin deficiency. Established pituitary provocation tests, however, failed to show a consistent increase in oxytocin levels. Several studies documented marked acute increases in circulating oxytocin levels in response to 3,4-methylenedioxymethamphetamine (MDMA, known as 'ecstasy') in healthy individuals explaining the empathic feelings and prosocial and anxiolytic effects of MDMA. Based on these results, the study team recently investigated MDMA as a novel provocation test for oxytocin deficiency in patients with AVP deficiency. The study team thereby demonstrated an additional oxytocin deficiency in patients with AVP deficiency using this novel stimulation test with MDMA. Results from this study demonstrate no or only minimal increase in oxytocin after MDMA intake in AVP deficiency while an almost 8-fold increase from baseline values in healthy controls. Acute oxytocin-induced effects under MDMA, such as increased trust, closeness, and openness to others, identification of facial emotions, and fear extinction, were significantly lower in patients compared to healthy controls. Based on this, the additional oxytocin deficiency could explain the psychopathology in patients. Given these data and evidence, oxytocin treatment to improve emotion recognition, decrease anxiety, and buffer effusive stress-induced cortisol increase would have great clinical implications. To date, the central effects of intranasal oxytocin in patients with AVP deficiency have not been addressed, and whether oxytocin administration in these patients can improve the psychological symptoms and provide a novel treatment option needs to be answered. Therefore, this case-control trial with randomized, placebo-controlled, double-blind, cross-over design aims to investigate the effects of a single dose of intranasal oxytocin compared to intranasal placebo on emotion recognition, and acute anxiety and cortisol in response to acute psychosocial stress in patients with AVP deficiency compared to healthy controls.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Part B oxytocin - Part A oxytocin - Part A Placebo - Part B Placebo
Part A will investigate the recognition of facial emotions \& body expressions in a cross-over design with a two-week wash-out period between both study visits. Part B will investigate the response of cortisol to acute psychosocial stress (TSST) with an eight-week wash-out period between both study visits. The order of group assignment is as follows: 1. Part B oxytocin, 2. Part A oxytocin, 3. Part A placebo, 4. Part B placebo
Intervention: Oxytocin nasal spray
Part B oxytocin - Part A oxytocin - Part A Placebo - Part B Placebo
Part A will investigate the recognition of facial emotions \& body expressions in a cross-over design with a two-week wash-out period between both study visits. Part B will investigate the response of cortisol to acute psychosocial stress (TSST) with an eight-week wash-out period between both study visits. The order of group assignment is as follows: 1. Part B oxytocin, 2. Part A oxytocin, 3. Part A placebo, 4. Part B placebo
Intervention: Placebo
Part B oxytocin - Part A Placebo - Part A oxytocin - Part B Placebo
Part A will investigate the recognition of facial emotions \& body expressions in a cross-over design with a two-week wash-out period between both study visits. Part B will investigate the response of cortisol to acute psychosocial stress (TSST) with an eight-week wash-out period between both study visits. The order of group assignment is as follows: 1. Part B oxytocin, 2. Part A placebo, 3. Part A oxytocin, 4. Part B placebo
Intervention: Oxytocin nasal spray
Part B oxytocin - Part A Placebo - Part A oxytocin - Part B Placebo
Part A will investigate the recognition of facial emotions \& body expressions in a cross-over design with a two-week wash-out period between both study visits. Part B will investigate the response of cortisol to acute psychosocial stress (TSST) with an eight-week wash-out period between both study visits. The order of group assignment is as follows: 1. Part B oxytocin, 2. Part A placebo, 3. Part A oxytocin, 4. Part B placebo
Intervention: Placebo
Part B Placebo - Part A Placebo - Part A oxytocin - Part B oxytocin
Part A will investigate the recognition of facial emotions \& body expressions in a cross-over design with a two-week wash-out period between both study visits. Part B will investigate the response of cortisol to acute psychosocial stress (TSST) with an eight-week wash-out period between both study visits. The order of group assignment is as follows: 1. Part B placebo, 2. Part A placebo, 3. Part A oxytocin, 4. Part B oxytocin
Intervention: Oxytocin nasal spray
Part B Placebo - Part A Placebo - Part A oxytocin - Part B oxytocin
Part A will investigate the recognition of facial emotions \& body expressions in a cross-over design with a two-week wash-out period between both study visits. Part B will investigate the response of cortisol to acute psychosocial stress (TSST) with an eight-week wash-out period between both study visits. The order of group assignment is as follows: 1. Part B placebo, 2. Part A placebo, 3. Part A oxytocin, 4. Part B oxytocin
Intervention: Placebo
Part B Placebo - Part A oxytocin - Part A Placebo - Part B oxytocin
Part A will investigate the recognition of facial emotions \& body expressions in a cross-over design with a two-week wash-out period between both study visits. Part B will investigate the response of cortisol to acute psychosocial stress (TSST) with an eight-week wash-out period between both study visits. The order of group assignment is as follows: 1. Part B placebo, 2. Part A oxytocin, 3. Part A placebo, 4. Part B oxytocin
Intervention: Oxytocin nasal spray
Part B Placebo - Part A oxytocin - Part A Placebo - Part B oxytocin
Part A will investigate the recognition of facial emotions \& body expressions in a cross-over design with a two-week wash-out period between both study visits. Part B will investigate the response of cortisol to acute psychosocial stress (TSST) with an eight-week wash-out period between both study visits. The order of group assignment is as follows: 1. Part B placebo, 2. Part A oxytocin, 3. Part A placebo, 4. Part B oxytocin
Intervention: Placebo
Outcomes
Primary Outcomes
Effect of oxytocin compared to placebo in patients with AVP deficiency compared to healthy controls on recognition of facial emotions/body expression
Time Frame: up to 4 weeks
Differences between the placebo and oxytocin session will be assessed for each participant in correct recognition of facial emotions \& body expressions assessed with the EmBody (emotion from body expressions) /EmFace (emotion from facial expressions) task of 3 or more score points (score range: 20-80) The EmBody and EmFace subtasks comprise each of 42 stimuli showing body or facial expressions of angry, happy, or neutral affect (14 clips per emotion, half in front view and half in half-profile side view from the left). Stimuli last 1.5 seconds at 24 frames per second and are geometrically and optically standardized to prevent biases induced by ethnic cues (e.g., hair or skin tone) or clothing. Item order is pseudorandom to prevent sequence effects and was determined using the following constraints: the same emotion is shown no more than twice in a row; the same view per emotion is not shown consecutively (i.e., no angry-front, angry-front).
Effect of oxytocin compared to placebo in patients with AVP deficiency compared to healthy controls cortisol in response to acute stress
Time Frame: up to 10 weeks
Differences between the placebo and oxytocin session will be assessed for each participant in cortisol levels in response to acute psychosocial stress induced upon the TSST (Trier Social Stress Test) by 15% or more in the area under the cortisol response curve. Salivary cortisol will be measured (as a measure of unbound cortisol concentrations in plasma) before and upon the TSST. Blood cortisol will also be measured The TSST consists of an unprepared speech and mental arithmetic performed in front of an audience. Previous studies indicated that this stress protocol reliably induces a significant HPA (Hypothalamic-pituitary-adrenal)-axis activation, with 2- to 3-fold increases in free cortisol and subjective responses indicative of moderate stress in healthy individuals.
Secondary Outcomes
- Emotion recognition(up to 4 weeks)
- Empathy(up to 4 weeks)
- Subjective emotional response to acute stress(up to 10 weeks)
- Heart rate (bpm)(up to 10 weeks)
- blood pressure (mmHG)(up to 10 weeks)