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

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

Study Overview

• Status: Completed
• Conditions: Diabetes Insipidus
• Intervention / Treatment: Diagnostic test: study intervention: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy); Diagnostic test: Control intervention: Placebo

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel, Endocrinology, Diabetes and Metabolism

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy volunteers	Diagnostic test: study intervention: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy); 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.; Diagnostic test: Control intervention: Placebo; Identical placebo (only mannitol) capsules
Experimental: Patients with central diabetes insipidus	Diagnostic test: study intervention: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy); 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.; Diagnostic test: Control intervention: Placebo; Identical placebo (only mannitol) capsules

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Mirjam Christ-Crain, Prof. Dr. med., Endocrinology, Diabetes and Metabolism, University Hospital Basel

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2021
• Primary Completion (Actual): April 11, 2022
• Study Completion (Actual): April 11, 2022

Study Registration Dates

• First Submitted: November 23, 2020
• First Submitted That Met QC Criteria: November 23, 2020
• First Posted (Actual): December 1, 2020

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 12, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: vasopressin; central diabetes insipidus; hypopituitarism; oxytocin levels; 3,4-methylenedioxymethamphetamine (MDMA); hypothalamic-pituitary axis
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Pituitary Diseases; Diabetes Mellitus; Diabetes Insipidus; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Hallucinogens; Adrenergic Uptake Inhibitors; N-Methyl-3,4-methylenedioxyamphetamine
• Other Study ID Numbers: 2020-02147; me20ChristCrain4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No