Diabetes Insipidus
Conditions
Keywords
central diabetes insipidus, oxytocin levels, 3,4-methylenedioxymethamphetamine (MDMA), hypothalamic-pituitary axis, hypopituitarism, vasopressin
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.
Interventions
DIAGNOSTIC_TESTControl intervention: Placebo
Identical placebo (only mannitol) capsules
DIAGNOSTIC_TESTstudy 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.
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 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 copeptin levels | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | Time course of copeptin 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 |
| Time course of prolactin levels | from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA | Time course of prolactin 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) |
| 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 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 |
| 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. |
| 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) |
Countries
Switzerland
Outcome results
None listed