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

University Hospital, Basel, Switzerland30 enrolled

Overview

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

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

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Diabetes Insipidus

Interventions

study intervention: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)DIAGNOSTIC_TEST

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.

Control intervention: PlaceboDIAGNOSTIC_TEST

Identical placebo (only mannitol) capsules

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

University Hospital Basel, Endocrinology, Diabetes and Metabolism

Basel, Switzerland

Outcomes

Primary Outcomes

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.