Autism Spectrum Disorder
Conditions
Keywords
Oxytocin (OT), 3,4-methylenedioxymethamphetamine (MDMA)
Brief summary
This study is to investigate the physiological mechanism of oxytocin system stimulation using 3,4-methylenedioxymethamphetamine (MDMA) as a physiological tool (acute oxytocin releases), not as a medication. This study seeks to test whether the oxytocin response after MDMA administration is different between individuals with autism spectrum disorder and matched healthy controls.
Detailed description
Oxytocin is a hypothalamic neuropeptide released both peripherally and centrally that modulates social behavior, emotional processing, and cognition through receptors in regions such as the amygdala, nucleus accumbens, and prefrontal cortex. Clinical, neurobiological, and genetic studies indicate altered oxytocin signaling in autism spectrum disorder (ASD): meta-analyses show lower peripheral oxytocin levels, reduced receptor binding in some brain areas (especially in females), and correlations between higher peripheral oxytocin receptor expression and better social functioning. Over the past two decades, oxytocin has been evaluated as a therapy for ASD, mainly to target social deficits. While exogenous oxytocin can transiently enhance social cognition and connectivity, long-term trials remain inconclusive. As with other hormone deficiencies, single basal oxytocin measurements are unreliable. An emerging alternative is the use of MDMA, which robustly increases circulating oxytocin concentrations in healthy individuals. Measuring oxytocin release after a standardized MDMA challenge could clarify whether ASD patients retain a functional oxytocinergic response, with a blunted release indicating pathway dysfunction. The OxySPECTRUM study will address this by administering a single dose of MDMA to high- functioning ASD patients and matched neurotypical controls, comparing plasma neurophysin I (equimolar oxytocin surrogate marker) area under curve (AUC) responses.
Interventions
DIAGNOSTIC_TESTMDMA
MDMA will be prepared as gelatine capsules containing 25 mg of pharmaceutically pure MDMA hydrochloride (Lipomed AG, Arlesheim, Switzerland) and mannitol filler. MDMA will be administered in a single dose of 100 mg (4 capsules of 25 mg MDMA)
DIAGNOSTIC_TESTPlacebo
Placebos will be prepared as identical gelatine capsules containing only mannitol filler.
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants, study investigators and study nurses will be blinded to the study intervention.
Intervention model description
Randomized, double-blind, placebo-controlled, cross-over (MDMA vs. placebo, within- individual comparison) study in patients versus healthy controls (between-individual comparison)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for patients: * Adult patients with a confirmed diagnosis of autism spectrum disorder level 1 according to Diagnostic and Statistical Manual (DSM) V Inclusion criteria for healthy controls: * Adult healthy controls * Matched for age, sex, BMI, and oestrogen replacement/menopause/hormonal contraceptives to patients * No medication, except hormonal contraception * A score of \<32 in the Autism Spectrum Quotient
Exclusion criteria
* Participation in a trial with investigational drugs within 30 days * Illicit substance use (except for 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/flutter, Wolff-Parkinson-White (WPW)-Syndrome) * Uncontrolled arterial hypertension (\>140/90 mmHg) or hypotension (\<85mmHg) * Current or previous major psychiatric disorder (e.g., major depression, schizophrenia spectrum disorder) * Psychotic disorder in first-degree relatives * Pregnancy and breastfeeding * Diagnosed CKD \> grade III (GFR \< 30ml/min) * Diagnosed liver cirrhosis or alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) levels 2.5 times above the normal range * Confirmed epilepsy diagnosis * Diagnosed autism spectrum disorder level 2 or 3 (according to DSM V criteria)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in area under the concentration time curve in plasma neurophysin I | From baseline (before intake) to 5 hours after a single dose administration of MDMA or placebo | Change in area under the concentration time curve in plasma neurophysin I after a single dose administration of MDMA (100mg) as compared to placebo in the same individuals and compared between ASD patients and healthy controls. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak change in plasma oxytocin/neurophysin-I level | From baseline (before intake) to 5 hours after a single dose administration of MDMA or placebo | — |
| Time course of plasma oxytocin/neurophysin-I levels | From baseline (before intake) to 5 hours after a single dose administration of MDMA or placebo | — |
| Time course of plasma MDMA concentration | From baseline (before intake) to 5 hours after a single dose administration of MDMA or placebo | — |
| Time course of pituitary hormone | From baseline (before intake) to 5 hours after a single dose administration of MDMA or placebo | — |
| Change in subjective emotional effects assessed on Subjective effects questionnaire Numeric Analog Scales (NAS) | Throughout the treatment visit (timepoint 0, 30, 60, 90, 120, 150, 180, 240, and 300 minutes) | Subjective emotional effects will be assessed repeatedly using the subjective/emotional effects questionnaire assessed with NAS. NAS will be presented as a range from 0 to 10 marked with "not at all" on the left and "extremely" on the right. |
| EmBody/EmFace Task | The test is performed once during each treatment visit and 2-2.5 hours after MDMA administration. | During the expected peak concentration of MDMA, participants will perform the EmBody/EmFace Task. Each of 42 stimuli showing body or facial expressions of angry, happy, or neutral affect (14 clips per emotion, half in front view and half in half-profile side view from the left). Stimuli last 1.5 seconds at 24 frames per second and are geometrically and optically standardized. Item order is pseudorandom to prevent sequence effects and was determined using the following constraints: the same emotion is shown no more than twice in a row; the same view per emotion is not shown consecutively (i.e., no angry-front, angry-front). |
| Facial emotion recognition task (FERT) | The test is performed once during each treatment visit and 2-2.5 hours after MDMA administration. | The FERT is used to assess recognition of basic emotions. The task includes 10 neutral faces and 160 faces that express one of four basic emotions (i.e., happiness, sadness, anger, and fear), with pictures morphed between 0% (neutral) and 100% in 10% steps. Two female and two male pictures are used for each of the four emotions. The outcome measure is accuracy (proportion correct). |
| Reading the Mind in the Eyes Test (RMET) | The test is administered once during each treatment visit and 2-2.5 hours after MDMA administration. | The RMET is used to assess theory of mind and emotion recognition from subtle facial cues. The task consists of 36 photographs showing only the eye region of male and female faces. For each photograph, four mental state descriptors (e.g., "anxious," "thoughtful," "playful," "serious") are presented, and participants are asked to choose the word that best matches what the person is feeling or thinking. Stimuli are displayed in random order without time restriction. The primary outcome measure is accuracy (proportion correct), with higher scores reflecting better social-cognitive performance. |
| Anxiety level with the State-Trait Anxiety Inventory (STAI) | The test requires about 5 minutes. | Based on responses to 20 items, with scores ranging from 1 ("almost never") to 4 ("almost always"), a total score is calculated. The total trait score (STAI-T) ranges from 20 to 80, with higher scores indicating more pronounced anxiety and scores. |
| Alexithymia level using the Toronto-Alexithymia-Scale 20 (TAS-20) | At the screening visit (about 2 minutes) | The TAS 20 has a three-factor structure: difficulty identifying feelings, difficulty describing feelings and externally oriented thinking. It includes 20 questions with scores ranging from 1 (strongly disagree) to 5 (strongly agree). |
| Depression level using the Beck Depression Inventory II (BDI-II) | At the screening visit (about 5 minutes) | The BDI II uses 21 items ranked from 0 (symptom absent) to 3 (severe symptoms) to measure the severity of depression. The minimum score is 0 and maximum score is 63. In non-clinical populations, scores above 20 indicate depression. In those diagnosed with depression, scores of 0-13 indicate minimal depression, 14-19 (mild depression), 20-28 (moderate depression) and 29-63 (severe depression). |
| General physical & mental health using the Patient-Reported Outcomes Measurement Information System (PROMIS) | At the screening visit (about 5 minutes) | The PROMIS is a set of person-centred measures that evaluate and monitor physical, mental, and social health. This questionnaire will consist of 29 items. In addition, cognitive functions consisting of 4 items and sociodemographic core data will be asked. |
| Autistic traits level using the Autism-Spectrum Quotient Test (AQ) | At the screening visit (about 5 minutes) | This questionnaire is a diagnostic test designed to measure the expression of ASD traits in an individual by his or her subjective self-assessment. The AQ consists of 50 items, with four choices for each item from "definitely agree" to "definitely disagree" and a total score from 0 to 50. A score above the proposed cut-off of 29 highlights significant traits of autism. |
| Autistic traits level using the Comprehensive Autistic Trait Inventory (CATI) | At the screening visit (about 5 minutes) | The CATI is a validated 42-item self-report questionnaire measuring autistic traits across six domains: Social Interactions, Communication, Social Camouflage, Repetitive Behaviours, Cognitive Rigidity, and Sensory Sensitivity. |
Countries
Switzerland
Contacts
CONTACTMirjam Christ-Crain, Prof. Dr. med.
CONTACTTalitha Hildebrandt
PRINCIPAL_INVESTIGATORMirjam Christ-Crain, Prof. Dr. med.
University Hospital Basel, Endocrinology, Diabetes and Metabolism
Outcome results
None listed