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

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ClinicalTrials.gov Identifier: NCT04648137
Recruitment Status : Completed
First Posted : December 1, 2020
Last Update Posted : April 13, 2022
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

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.

Condition or disease Intervention/treatment Phase
Diabetes Insipidus Diagnostic Test: study intervention: 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) Diagnostic Test: Control intervention: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Circulating Oxytocin Changes in Response to the Oxytocin System Stimulator MDMA in Patients With Diabetes Insipidus and Healthy Controls
Actual Study Start Date : February 5, 2021
Actual Primary Completion Date : April 11, 2022
Actual Study Completion Date : April 11, 2022


Arm Intervention/treatment
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

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




Primary Outcome Measures :
  1. area under the concentration time curve in oxytocin level [ Time Frame: 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 Outcome Measures :
  1. Peak change in oxytocin (OT) plasma level [ Time Frame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA ]
    Peak change in OT plasma level

  2. Time course of plasma OT levels [ Time Frame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA ]
    Time course of plasma OT levels

  3. Time course of plasma MDMA concentration [ Time Frame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA ]
    Time course of plasma MDMA concentration

  4. Time course of cortisol levels [ Time Frame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA ]
    Time course of cortisol levels

  5. Time course of prolactin levels [ Time Frame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA ]
    Time course of prolactin levels

  6. Time course of copeptin levels [ Time Frame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA ]
    Time course of copeptin levels

  7. Time course of adrenocorticotropic hormone (ACTH) levels [ Time Frame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA ]
    Time course of ACTH levels

  8. Subjective/emotional effects [ Time Frame: 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)

  9. 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 ]
    Recognition of negative emotions in the face emotion recognition task (FERT)

  10. Empathy in the multifaceted empathy task (MET) [ Time Frame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA ]
    Empathy in the multifaceted empathy task (MET)

  11. Anxiety level with the State-Trait Anxiety Inventory (STAI) [ Time Frame: from baseline oxytocin measurement (before intake) to 6 hours after administration of MDMA ]
    Anxiety level with the State-Trait Anxiety Inventory (STAI)

  12. Level of Alexithymia using the Toronto-Alexithymia-Scale 20 (TAS-20) [ Time Frame: 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

  13. Level of depression using the Beck-Depressions-Inventory II (BDI-II) [ Time Frame: 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.

  14. Level of general physical & mental health using the short form health survey (SF-36) [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04648137


Locations
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Switzerland
University Hospital Basel, Endocrinology, Diabetes and Metabolism
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
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Principal Investigator: Mirjam Christ-Crain, Prof. Dr. med. Endocrinology, Diabetes and Metabolism, University Hospital Basel
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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT04648137    
Other Study ID Numbers: 2020-02147; me20ChristCrain4
First Posted: December 1, 2020    Key Record Dates
Last Update Posted: April 13, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Basel, Switzerland:
central diabetes insipidus
oxytocin levels
3,4-methylenedioxymethamphetamine (MDMA)
hypothalamic-pituitary axis
hypopituitarism
vasopressin
Additional relevant MeSH terms:
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Diabetes Insipidus
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Kidney Diseases
Urologic Diseases
Pituitary Diseases
N-Methyl-3,4-methylenedioxyamphetamine
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Adrenergic Agents