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

NCT ID: NCT04648137

Last Updated: 2022-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-05
• Study Completion Date: 2022-04-11

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.

Conditions

Diabetes Insipidus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Patients with central diabetes insipidus

Group Type: EXPERIMENTAL

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

Intervention Type: 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: Placebo

Intervention Type: DIAGNOSTIC_TEST

Identical placebo (only mannitol) capsules

Healthy volunteers

Group Type: EXPERIMENTAL

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

Intervention Type: 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: Placebo

Intervention Type: DIAGNOSTIC_TEST

Identical placebo (only mannitol) capsules

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

Control intervention: Placebo

Identical placebo (only mannitol) capsules

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of central diabetes insipidus

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mirjam Christ-Crain, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Endocrinology, Diabetes and Metabolism, University Hospital Basel

Locations

University Hospital Basel, Endocrinology, Diabetes and Metabolism

Basel, , Switzerland

Countries

Switzerland

References

Atila C, Holze F, Murugesu R, Rommers N, Hutter N, Varghese N, Sailer CO, Eckert A, Heinrichs M, Liechti ME, Christ-Crain M. Oxytocin in response to MDMA provocation test in patients with arginine vasopressin deficiency (central diabetes insipidus): a single-centre, case-control study with nested, randomised, double-blind, placebo-controlled crossover trial. Lancet Diabetes Endocrinol. 2023 Jul;11(7):454-464. doi: 10.1016/S2213-8587(23)00120-1. Epub 2023 May 13.

Reference Type: DERIVED

PMID: 37192642 (View on PubMed)

Other Identifiers

2020-02147; me20ChristCrain4

Identifier Type: -

Identifier Source: org_study_id