Pharmacological Interaction Between Clonidine and Methylenedioxymethamphetamine (MDMA)

• ClinicalTrials.gov Identifier: NCT01136278
• Recruitment Status: Completed
• First Posted: June 3, 2010
• Last Update Posted: January 25, 2013
• Sponsor: University Hospital, Basel, Switzerland
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Tracking Information

• First Submitted Date: May 31, 2010
• First Posted Date: June 3, 2010
• Last Update Posted Date: January 25, 2013
• Study Start Date: July 2010
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 2, 2010): Effect of clonidine on the subjective response to MDMA [ Time Frame: 24 h ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 2, 2010)

• Effect of clonidine on cardiovascular effects of MDMA [ Time Frame: 8 h ]
• Effect of clonidine on pharmacokinetics of MDMA [ Time Frame: 8 h ]
• Effect of MDMA on clonidine pharmacokinetics [ Time Frame: 8 h ]
• Tolerability of MDMA and clonidine [ Time Frame: 8 h ]
• Effect of clonidine on neuroendocrine responses to MDMA [ Time Frame: 8 h ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: January 24, 2013)

Genetic polymorphisms [ Time Frame: assessed after study completion ]

Effects of genetic polymorphisms on the response to MDMA

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pharmacological Interaction Between Clonidine and Methylenedioxymethamphetamine (MDMA)
• Official Title: Pharmacological Interaction Between Clonidine and 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)
• Brief Summary: The purpose of this study is to determinate the effect of a pre-treatment with centrally acting alpha2-receptor agonist clonidine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"). The investigators hypothesize that clonidine will attenuate the subjective and cardiovascular response to MDMA.
• Detailed Description: 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is widely used by young people for its euphoric effects. MDMA releases serotonin (5-HT), norepinephrine (NE), and dopamine. It is unknown which of these monoamines mainly contributes to the subjective and physiological effects of MDMA in humans. Clonidine is a centrally acting alpha2-receptor agonist and sympatholytic which attenuates the release of NE from presynaptic nerve terminals and also lowers NE plasma concentration. To determine the role of NE in the response to MDMA in humans we test the effects of a clonidine pretreatment on the pharmacodynamics and pharmacokinetics of MDMA. We use a randomized double-blind placebo-controlled cross-over design with four experimental sessions. Clonidine (150 μg) or placebo will be administered 1 h before the administration of MDMA (125 mg) or placebo to 16 healthy volunteers. Subjective and cardiovascular responses will be repeatedly assessed throughout the experiments and plasma samples are collected for pharmacokinetics. We hypothesize that clonidine will significantly attenuate predominantly the cardiovascular response to MDMA.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science

Condition

• Mood Disorder
• Substance-Related Disorders
• Amphetamine-Related Disorders

Intervention

• Drug: 3,4-Methylenedioxymethamphetamine
  125 mg, single dose
  Other Names:

  • MDMA
  • Ecstasy
• Drug: Clonidine
  150 μg per os
• Drug: placebo
  capsules identical to MDMA or clonidine

Study Arms

Experimental: clonidine, MDMA, placebo

Cross-over within-subjects design with all treatment conditions tested in the same subject. This design has 1 arm but two (actually 4) treatment conditions in the same subject.

Interventions:

• Drug: 3,4-Methylenedioxymethamphetamine
• Drug: Clonidine
• Drug: placebo

Publications *

• Vizeli P, Liechti ME. Oxytocin receptor gene variations and socio-emotional effects of MDMA: A pooled analysis of controlled studies in healthy subjects. PLoS One. 2018 Jun 18;13(6):e0199384. doi: 10.1371/journal.pone.0199384. eCollection 2018.
• Hysek CM, Liechti ME. Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex. Psychopharmacology (Berl). 2012 Dec;224(3):363-76. doi: 10.1007/s00213-012-2761-6. Epub 2012 Jun 15.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 2, 2010): 16
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2010
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Sufficient understanding of the German language
• Subjects understand the procedures and the risks associated with the study
• Participants must be willing to adhere to the protocol and sign the consent form
• Participants must be willing to refrain from taking illicit psychoactive substances during the study.
• Participants must be willing to drink only alcohol-free liquids and no xanthine-containing liquids (such as coffee, black or green tea, red bull, chocolate) after midnight of the evening before the study session. Subjects must agree not to smoke tobacco for 1 h before and 4 hours after MDMA administration.
• Participants must be willing not to drive a traffic vehicle in the evening of the study day.
• Women of childbearing potential must have a negative pregnancy test at the beginning of the study and must agree to use an effective form of birth control. Pregnancy tests are repeated before each study session.
• Body mass index: 18-25 kg/m2

Exclusion Criteria:

• Chronic or acute medical condition including clinically relevant abnormality in physical exam, laboratory values, or ECG. In particular: Hypertension (>140/90 mmHg). Personal or first-grade history of seizures. Cardiac or neurological disorder.
• Current or previous psychotic or affective disorder
• Psychotic or affective disorder in first-degree relatives
• Prior illicit drug use (except THC (Tetrahydrocannabinol)-containing products) more than 5 times or any time within the previous 2 months.
• Pregnant or nursing women.
• Participation in another clinical trial (currently or within the last 30 days)
• Use of medications that are contraindicated or otherwise interfere with the effects of the study medications (monoamine oxidase inhibitors, antidepressants, sedatives etc.)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT01136278
• Other Study ID Numbers: EK 353/09
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University Hospital, Basel, Switzerland
• Study Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Not Provided

Investigators

• Principal Investigator: Matthias E Liechti, MD; Department of Internal Medicine, Division of Pharmacology & Toxicology, University Hospital Basel, Switzerland

• PRS Account: University Hospital, Basel, Switzerland
• Verification Date: January 2013