Circulating Oxytocin Changes in Response to the Oxytocin System Stimulator MDMA in Patients With Diabetes Insipidus and Healthy Controls

Study Overview
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Brief Summary
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This study is to evaluate oxytocin levels in response to MDMA administration as compared to placebo in patients with diabetes insipidus and healthy volunteers.

Detailed Description
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Disruption of the hypothalamic-pituitary axis due to congenital abnormalities, tumors or head trauma may cause anterior and/or posterior pituitary deficiency also known as partial or panhypopituitarism. Patients with hypopituitarism, especially those with panhypopituitarism (i.e., anterior and posterior insufficiency) often report residual symptoms and lower quality of life despite adequate substitution treatment of deficient pituitary hormones. A recent study identified a potential oxytocin deficient state in men with combined anterior and posterior deficiency. Due to the close proximity of vasopressin and oxytocin, disruption of the vasopressin system leading to diabetes insipidus could as well disturb the oxytocin system leading to low oxytocin levels. It is therefore possible that the increased psychopathology and reduced quality of life as observed in patients with central diabetes insipidus is caused by an oxytocin deficiency. Several studies documented marked acute increases in circulating oxytocin levels in response to 3,4-methylenedioxymethamphetamine (MDMA) administration as compared to placebo in healthy volunteers. MDMA could therefore be useful as a provocation test to detect an oxytocin deficiency in patients with central diabetes insipidus. This study is to investigate if oxytocin provocation following a single dose administration of MDMA is reduced in patients with central diabetes insipidus as compared to healthy volunteers.

Official Title
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Circulating Oxytocin Changes in Response to the Oxytocin System Stimulator MDMA in Patients With Diabetes Insipidus and Healthy Controls

Conditions
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Diabetes Insipidus

Intervention / Treatment
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* Diagnostic Test: study intervention: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)
* Diagnostic Test: Control intervention: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria diabetes insipidus: Confirmed diagnosis of central diabetes insipidus Inclusion criteria healthy volunteers: Matched for age, sex, BMI and estrogen replacement/menopause/hormonal contraceptives to patients with central diabetes insipidus No medication, except hormonal contraception- Exclusion Criteria: Familial central diabetes insipidus Participation in a trial with investigational drugs within 30 days Illicit substance use (with the exception of cannabis) more than 10 times in lifetime or any time within the previous two months Consumption of alcoholic beverages >15 drinks/week Tobacco smoking >10 cigarettes/day Cardiovascular disease (coronary artery disease, heart failure, left ventricular ejection fraction ( LVEF) <40%, stroke in the last 3 months, atrial fibrillation/flatter, Wolff-Parkinson-White syndrome (WPW)-Syndrome) Uncontrolled arterial hypertension (>140/90 mmHg) or hypotension (syst blood pressure <85mmHg) Current or previous major psychiatric disorder (e.g., major depression, schizophrenia spectrum disorder) Psychotic disorder in first-degree relatives Regular intake of selective serotonin reuptake inhibitor (SSRI), monoamine oxidase (MAO)-Inhibitors Pregnancy and breastfeeding Diagnosed chronic kidney disease (CKD) > grade III (GRF < 30ml/min) Diagnosed liver cirrhosis or alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) levels 2.5 times above the normal range

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled, cross-over (MDMA versus placebo, within subject comparison) study in patients with central diabetes insipidus versus healthy controls (between-subject comparison). Participants will be randomized to receive either first placebo or first MDMA, respectively.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with central diabetes insipidus<br> | Diagnostic Test: study intervention: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)<br>* single administration of MDMA (100mg): 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) will be prepared as gelatin capsules with mannitol as the filler. MDMA will be administered in a single absolute dose of 100 mg corresponding to a medium high dose of (mean ± SD) 1.3 ± 0.3 mg/kg body weight.<br>Diagnostic Test: Control intervention: Placebo<br>* Identical placebo (only mannitol) capsules<br>|
| Experimental: Healthy volunteers<br> | Diagnostic Test: study intervention: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)<br>* single administration of MDMA (100mg): 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) will be prepared as gelatin capsules with mannitol as the filler. MDMA will be administered in a single absolute dose of 100 mg corresponding to a medium high dose of (mean ± SD) 1.3 ± 0.3 mg/kg body weight.<br>Diagnostic Test: Control intervention: Placebo<br>* Identical placebo (only mannitol) capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| area under the concentration time curve in oxytocin level | area under the concentration time curve in oxytocin level from baseline oxytocin measurement (before intake) to 6 hours after a single administration of MDMA (100mg) as compared to placebo in the same subjects between patients with central diabetes insipidus and healthy volunteers. | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak change in oxytocin (OT) plasma level | Peak change in OT plasma level | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Time course of plasma OT levels | Time course of plasma OT levels | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Time course of plasma MDMA concentration | Time course of plasma MDMA concentration | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Time course of cortisol levels | Time course of cortisol levels | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Time course of prolactin levels | Time course of prolactin levels | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Time course of copeptin levels | Time course of copeptin levels | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Time course of adrenocorticotropic hormone (ACTH) levels | Time course of ACTH levels | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Subjective/emotional effects | Subjective/emotional effects assessed on a 10-point visual analog scale (e.g., feelings of anxiety, pleasure, fear, 0 = better outcome,10 = worst outcome) | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Recognition of negative emotions in the face emotion recognition task (FERT) | Recognition of negative emotions in the face emotion recognition task (FERT) | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Empathy in the multifaceted empathy task (MET) | Empathy in the multifaceted empathy task (MET) | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Anxiety level with the State-Trait Anxiety Inventory (STAI) | Anxiety level with the State-Trait Anxiety Inventory (STAI) | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Level of Alexithymia using the Toronto-Alexithymia-Scale 20 (TAS-20) | Level of Alexithymia using the Toronto-Alexithymia-Scale 20 (TAS-20); total scores can range from 20-100, with higher scores indicating greater impairment/challenges | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Level of depression using the Beck-Depressions-Inventory II (BDI-II) | Level of depression using the Beck-Depressions-Inventory II (BDI-II); 21-question multiple-choice self-report inventory. Higher total scores indicate more severe depressive symptoms. | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 
| Level of general physical & mental health using the short form health survey (SF-36) | Level of general physical & mental health using the short form health survey (SF-36); 36-item, patient-reported survey of patient health; the higher the score, the more favourable the health state. | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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central diabetes insipidus, oxytocin levels, 3,4-methylenedioxymethamphetamine (MDMA), hypothalamic-pituitary axis, hypopituitarism, vasopressin