Clinical trial NCT04648137: Circulating Oxytocin Changes in Response to the Oxytocin System Stimulator MDMA in Patients With Diabetes Insipidus and Healthy Controls
Official title: Circulating Oxytocin Changes in Response to the Oxytocin System Stimulator MDMA in Patients With Diabetes Insipidus and Healthy Controls
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Insipidus
Keywords: central diabetes insipidus
oxytocin levels
3,4-methylenedioxymethamphetamine (MDMA)
hypothalamic-pituitary axis
hypopituitarism
vasopressin
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2020-12-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: area under the concentration time curve in oxytocin level
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Secondary outcomes:
measure: Peak change in oxytocin (OT) plasma level
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Time course of plasma OT levels
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Time course of plasma MDMA concentration
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Time course of cortisol levels
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Time course of prolactin levels
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Time course of copeptin levels
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Time course of adrenocorticotropic hormone (ACTH) levels
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Subjective/emotional effects
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Recognition of negative emotions in the face emotion recognition task (FERT)
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Empathy in the multifaceted empathy task (MET)
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Anxiety level with the State-Trait Anxiety Inventory (STAI)
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Level of Alexithymia using the Toronto-Alexithymia-Scale 20 (TAS-20)
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Level of depression using the Beck-Depressions-Inventory II (BDI-II)
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
measure: Level of general physical & mental health using the short form health survey (SF-36)
timeFrame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Endocrinology, Diabetes and Metabolism
Study officials:
affiliation: Endocrinology, Diabetes and Metabolism, University Hospital Basel
name: Mirjam Christ-Crain, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: