Effect of Methylenedioxymethamphetamine (MDMA) (Serotonin Release) on Fear Extinction (MFE)

• ClinicalTrials.gov Identifier: NCT03527316
• Recruitment Status: Completed
• First Posted: May 17, 2018
• Last Update Posted: January 19, 2022
• Sponsor: University Hospital, Basel, Switzerland
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Tracking Information

• First Submitted Date: May 4, 2018
• First Posted Date: May 17, 2018
• Last Update Posted Date: January 19, 2022
• Actual Study Start Date: October 18, 2019
• Actual Primary Completion Date: December 10, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 4, 2018)

• Fear extinction measured by Skin conductance response [ Time Frame: 12 months ]
  a) Skin conductance response to conditioned stimuli
• Fear extinction measured by Fear-potentiated startle [ Time Frame: 12 months ]
  b) Fear-potentiated startle to conditioned stimuli

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 16, 2018)

• Plasma concentration of Oxytocin [ Time Frame: 12 months ]
• Subjective effects measured by Visual analog scales [ Time Frame: 12 months ]
  Visual analog scales, 0-100, 0 for 'not at all' and 100 for 'extremely'
• Autonomic effects measured by Blood pressure [ Time Frame: 12 months ]
  Autonomic effects measured by vital signs
• Autonomic effects measured by Hearth rate [ Time Frame: 12 months ]
  Autonomic effects measured by vital signs
• Autonomic effects measured by Body temperature [ Time Frame: 12 months ]
  Autonomic effects measured by vital signs
• Subjective effects measured by State-trait anxiety inventory for state (STAI-S) [ Time Frame: 12 months ]
• Plasma concentration of MDMA [ Time Frame: 12 months ]

Original Secondary Outcome Measures (submitted: May 4, 2018)

• Plasma concentration of Oxytocin [ Time Frame: 12 months ]
• Subjective effects measured by Visual analog scales [ Time Frame: 12 months ]
  Visual analog scales (VAS)
• Autonomic effects measured by Blood pressure [ Time Frame: 12 months ]
  Autonomic effects measured by vital signs
• Autonomic effects measured by Hearth rate [ Time Frame: 12 months ]
  Autonomic effects measured by vital signs
• Autonomic effects measured by Body temperature [ Time Frame: 12 months ]
  Autonomic effects measured by vital signs
• Subjective effects measured by State-trait anxiety inventory for state (STAI-S) [ Time Frame: 12 months ]
• Plasma concentration of MDMA [ Time Frame: 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of Methylenedioxymethamphetamine (MDMA) (Serotonin Release) on Fear Extinction
• Official Title: Effect of MDMA (Serotonin Release) on Fear Extinction
• Brief Summary: Serotonin and oxytocin play a role in fear conditioning and fear extinction learning, psychological processes that are critically involved in psychiatric disorders such as posttraumatic stress disorder (PTSD). Specifically, administration of oxytocin has been shown to facilitate fear extinction in humans. Similarly, substances that release serotonin and oxytocin such as MDMA have been shown to enhance the extinction of fear memory in animals. However, there are no data on the effects of MDMA on fear extinction in humans. Therefore, the primary aim of this study is to investigate the role of acute serotonin release in the effects of fear extinction. MDMA will be used as pharmacological tool to induce serotonin release in this study.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Healthy

Intervention

• Drug: MDMA
  125 mg MDMA per os, single dose
  Other Name: 3,4-Methylenedioxymethamphetamine
• Drug: Placebo
  Capsules containing mannitol looking identical to the other drugs.

Study Arms

• Experimental: MDMA, Placebo
  Cross-over within-subjects design with both treatment conditions, separated by a wash-out phase
  Interventions:

  • Drug: MDMA
  • Drug: Placebo
• Experimental: Placebo, MDMA
  Cross-over within-subjects design with both treatment conditions, separated by a wash-out phase
  Interventions:

  • Drug: MDMA
  • Drug: Placebo

• Publications *: Vizeli P, Straumann I, Duthaler U, Varghese N, Eckert A, Paulus MP, Risbrough V, Liechti ME. Effects of 3,4-Methylenedioxymethamphetamine on Conditioned Fear Extinction and Retention in a Crossover Study in Healthy Subjects. Front Pharmacol. 2022 Jul 13;13:906639. doi: 10.3389/fphar.2022.906639. eCollection 2022.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 4, 2018): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 24, 2020
• Actual Primary Completion Date: December 10, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male
• Age between 18 and 50 years.
• Understanding of the German language.
• Understanding 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 coffee, black or green tea, or energy drink after midnight of the evening before the study session, as well as during the study day.
• Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
• Body mass index 18-29 kg/m2.

Exclusion Criteria:

• Chronic or acute medical condition
• Hypertension (>140/90 mmHg) or hypotension (SBP<85 mmHg)
• Current or previous major psychiatric disorder
• Psychotic disorder in first-degree relatives
• Illicit substance use (with the exception of cannabis) of more than 5 times or any time within the previous month.
• Participation in another clinical trial (currently or within the last 30 days)
• Use of medications that may interfere with the effects of the study medications (any psychiatric medications)
• Tobacco smoking (>10 cigarettes/day)
• Consumption of alcoholic standard drinks (>10/week or >120 g ethanol/week)

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 50 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: NCT03527316
• Other Study ID Numbers: BASEC 2017-01947
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University Hospital, Basel, Switzerland
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Basel, Switzerland
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Matthias E Liechti, MD, MAS; University Hospital, Basel, Switzerland

• PRS Account: University Hospital, Basel, Switzerland
• Verification Date: January 2022