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

Not Applicable

Completed

• Conditions: Diabetes Insipidus

• Registration Number: NCT04648137
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-11-23
• Study First Submitted QC: 2020-11-23
• Study First Posted: 2020-12-01
• Study Start: 2021-02-05
• Status Verified: 2022-04
• Primary Completion: 2022-04-11
• Study Completion: 2022-04-11
• Last Update Submitted: 2022-04-12
• Last Update Posted: 2022-04-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
area under the concentration time curve in oxytocin level	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	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.

Secondary Outcome Measures

Name	Time	Method
Time course of plasma OT levels	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	Time course of plasma OT levels
Time course of prolactin levels	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	Time course of prolactin levels
Empathy in the multifaceted empathy task (MET)	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	Empathy in the multifaceted empathy task (MET)
Anxiety level with the State-Trait Anxiety Inventory (STAI)	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	Anxiety level with the State-Trait Anxiety Inventory (STAI)
Level of general physical & mental health using the short form health survey (SF-36)	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); 36-item, patient-reported survey of patient health; the higher the score, the more favourable the health state.
Subjective/emotional effects	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	Subjective/emotional effects assessed on a 10-point visual analog scale (e.g., feelings of anxiety, pleasure, fear, 0 = better outcome,10 = worst outcome)
Peak change in oxytocin (OT) plasma level	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	Peak change in OT plasma level
Time course of copeptin levels	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	Time course of copeptin levels
Recognition of negative emotions in the face emotion recognition task (FERT)	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	Recognition of negative emotions in the face emotion recognition task (FERT)
Level of depression using the Beck-Depressions-Inventory II (BDI-II)	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	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.
Time course of plasma MDMA concentration	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	Time course of plasma MDMA concentration
Time course of cortisol levels	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	Time course of cortisol levels
Time course of adrenocorticotropic hormone (ACTH) levels	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	Time course of ACTH levels
Level of Alexithymia using the Toronto-Alexithymia-Scale 20 (TAS-20)	from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA	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

Trial Locations

Locations (1)

University Hospital Basel, Endocrinology, Diabetes and Metabolism; 🇨🇭 Basel, Switzerland