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

Primary Purpose

Diabetes Insipidus

Status
Completed
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
study intervention: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)
Control intervention: Placebo
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Diabetes Insipidus focused on measuring central diabetes insipidus, oxytocin levels, 3,4-methylenedioxymethamphetamine (MDMA), hypothalamic-pituitary axis, hypopituitarism, vasopressin

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University Hospital Basel, Endocrinology, Diabetes and Metabolism

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Patients with central diabetes insipidus

Healthy volunteers

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Peak change in oxytocin (OT) plasma level
Peak change in OT plasma level
Time course of plasma OT levels
Time course of plasma OT levels
Time course of plasma MDMA concentration
Time course of plasma MDMA concentration
Time course of cortisol levels
Time course of cortisol levels
Time course of prolactin levels
Time course of prolactin levels
Time course of copeptin levels
Time course of copeptin levels
Time course of adrenocorticotropic hormone (ACTH) levels
Time course of ACTH levels
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)
Recognition of negative emotions in the face emotion recognition task (FERT)
Recognition of negative emotions in the face emotion recognition task (FERT)
Empathy in the multifaceted empathy task (MET)
Empathy in the multifaceted empathy task (MET)
Anxiety level with the State-Trait Anxiety Inventory (STAI)
Anxiety level with the State-Trait Anxiety Inventory (STAI)
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
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.
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.

Full Information

First Posted
November 23, 2020
Last Updated
April 12, 2022
Sponsor
University Hospital, Basel, Switzerland
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1. Study Identification

Unique Protocol Identification Number
NCT04648137
Brief Title
Circulating Oxytocin Changes in Response to the Oxytocin System Stimulator MDMA in Patients With Diabetes Insipidus and Healthy Controls
Acronym
OxyMA
Official Title
Circulating Oxytocin Changes in Response to the Oxytocin System Stimulator MDMA in Patients With Diabetes Insipidus and Healthy Controls
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
February 5, 2021 (Actual)
Primary Completion Date
April 11, 2022 (Actual)
Study Completion Date
April 11, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Insipidus
Keywords
central diabetes insipidus, oxytocin levels, 3,4-methylenedioxymethamphetamine (MDMA), hypothalamic-pituitary axis, hypopituitarism, vasopressin

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
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.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patients with central diabetes insipidus
Arm Type
Experimental
Arm Title
Healthy volunteers
Arm Type
Experimental
Intervention Type
Diagnostic Test
Intervention Name(s)
study intervention: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)
Intervention Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
Control intervention: Placebo
Intervention Description
Identical placebo (only mannitol) capsules
Primary Outcome Measure Information:
Title
area under the concentration time curve in oxytocin level
Description
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.
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Secondary Outcome Measure Information:
Title
Peak change in oxytocin (OT) plasma level
Description
Peak change in OT plasma level
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Time course of plasma OT levels
Description
Time course of plasma OT levels
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Time course of plasma MDMA concentration
Description
Time course of plasma MDMA concentration
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Time course of cortisol levels
Description
Time course of cortisol levels
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Time course of prolactin levels
Description
Time course of prolactin levels
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Time course of copeptin levels
Description
Time course of copeptin levels
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Time course of adrenocorticotropic hormone (ACTH) levels
Description
Time course of ACTH levels
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Subjective/emotional effects
Description
Subjective/emotional effects assessed on a 10-point visual analog scale (e.g., feelings of anxiety, pleasure, fear, 0 = better outcome,10 = worst outcome)
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Recognition of negative emotions in the face emotion recognition task (FERT)
Description
Recognition of negative emotions in the face emotion recognition task (FERT)
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Empathy in the multifaceted empathy task (MET)
Description
Empathy in the multifaceted empathy task (MET)
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Anxiety level with the State-Trait Anxiety Inventory (STAI)
Description
Anxiety level with the State-Trait Anxiety Inventory (STAI)
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Level of Alexithymia using the Toronto-Alexithymia-Scale 20 (TAS-20)
Description
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
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Level of depression using the Beck-Depressions-Inventory II (BDI-II)
Description
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 Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA
Title
Level of general physical & mental health using the short form health survey (SF-36)
Description
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.
Time Frame
from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mirjam Christ-Crain, Prof. Dr. med.
Organizational Affiliation
Endocrinology, Diabetes and Metabolism, University Hospital Basel
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Basel, Endocrinology, Diabetes and Metabolism
City
Basel
ZIP/Postal Code
4031
Country
Switzerland

12. IPD Sharing Statement

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

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