Back to results

Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine: Pharmacodynamics (PD) and Pharmacokinetics (PK)

Primary Purpose

Mood Disorder, Substance-related Disorders, Amphetamine-related Disorders

Status

Completed

Phase

Phase 1

Locations

Switzerland

Study Type

Interventional

Intervention

MDMA

Reboxetine, 8 mg

Placebo

About this trial

This is an interventional basic science trial for Mood Disorder focused on measuring MDMA, norepinephrine, Ecstasy, stimulant

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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 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.)

Sites / Locations

University Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Reboxetine, MDMA, Placebo

Arm Description

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.

Outcomes

Primary Outcome Measures

Effect of reboxetine on subjective responses to MDMA

Secondary Outcome Measures

Effect of reboxetine on physiological responses to MDMA

Effects of reboxetine on pharmacokinetics of MDMA

Tolerability of MDMA and reboxetine

Effect of reboxetine on neuroendocrine responses to MDMA

Full Information

NCT ID

NCT00886886

First Posted

April 22, 2009

Last Updated

January 24, 2013

Sponsor

University Hospital, Basel, Switzerland

1. Study Identification

Unique Protocol Identification Number

NCT00886886

Brief Title

Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine: Pharmacodynamics (PD) and Pharmacokinetics (PK)

Official Title

Pharmacological Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy): Pharmacological Effects and Pharmacokinetics

Study Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Completed

Study Start Date

April 2009 (undefined)

Primary Completion Date

December 2009 (Actual)

Study Completion Date

March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Basel, Switzerland

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

MDMA releases dopamine, serotonin, and norepinephrine in the brain. Serotonin uptake inhibitors have been shown to interact with 3,4-Methylenedioxymethamphetamine (MDMA) and to decrease its psychoactive and cardiovascular stimulant effects. This finding indicates that MDMA acts in part by releasing serotonin through the serotonin uptake site. However, in vitro studies show that MDMA binds more potently to the norepinephrine uptake site that to the the serotonin or dopamine uptake transporter. In addition, norepinephrine uptake site blockers such antidepressant drugs attenuate some of the behavioral effects of MDMA in animals. These preclinical data indicate that norepinephrine may also contribute to the response to MDMA in humans. To test this hypothesis this study evaluates the interacting effects of the selective norepinephrine transporter inhibitor reboxetine on the subjective and cardiovascular stimulant effects of MDMA in healthy volunteers.

Detailed Description

The study will use a randomized double-blind cross-over design with four experimental sessions. Reboxetine (8 mg) or placebo will be administered the night before the experimental session and 1 h before the administration of MDMA (125 mg) or placebo to 16 healthy volunteers. Subjective and cardiovascular responses and plasma samples for pharmacokinetics will be repeatedly assessed throughout the experiments. We hypothesize that the highly selective norepinephrine uptake inhibitor reboxetine will attenuate subjective and especially heart rate and blood pressure responses to MDMA. Such a result would indicate that norepinephrine is critically involved in the pharmacology of MDMA and may provide helpful in the use and development of treatments for Ecstasy intoxications.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mood Disorder, Substance-related Disorders, Amphetamine-related Disorders

Keywords

MDMA, norepinephrine, Ecstasy, stimulant

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Reboxetine, MDMA, Placebo

Arm Type

Other

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

MDMA

Intervention Description

125 mg, single dose

Intervention Type

Drug

Intervention Name(s)

Reboxetine, 8 mg

Intervention Description

two doses 12h and 2h before MDMA

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

capsules identical to MDMA or Reboxetine

Primary Outcome Measure Information:

Title

Effect of reboxetine on subjective responses to MDMA

Time Frame

24h

Secondary Outcome Measure Information:

Title

Effect of reboxetine on physiological responses to MDMA

Time Frame

24h

Title

Effects of reboxetine on pharmacokinetics of MDMA

Time Frame

24h

Title

Tolerability of MDMA and reboxetine

Time Frame

7 days

Title

Effect of reboxetine on neuroendocrine responses to MDMA

Time Frame

24h

Other Pre-specified Outcome Measures:

Title

Genetic polymorphisms

Description

Effects of genetic polymorphisms on the response to MDMA

Time Frame

assessed after study completion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

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 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.)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Matthias E Liechti, MD

Organizational Affiliation

Department of Internal Medicine, Division of Pharmacology & Toxicology, University Hospital Basel, Switzerland

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital

City

Basel

Country

Switzerland

12. IPD Sharing Statement

Citations:

PubMed Identifier

29912955

Citation

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.

Results Reference

derived

PubMed Identifier

22700038

Citation

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.

Results Reference

derived

Learn more about this trial

Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine: Pharmacodynamics (PD) and Pharmacokinetics (PK)

We'll reach out to this number within 24 hrs