Clinical trial NCT03181763: Evaluation of MDMA on Startle Response
Official title: Evaluation of 3,4-methylenedioxymethamphetamine (MDMA) on Startle Response
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Startle Response
Keywords: MDMA
Startle response
sleep
Oxytocin
Lead sponsor: Lykos Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-06-09
Enrollment: 34
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Blinded, placebo between group; all participants undergo fear conditioning, with half randomized to receive 100 mg MDMA and half receiving inactive placebo
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this clinical trial is to learn if MDMA impacts startle response in healthy participants.

The main question it aims to answer is: Does MDMA impact participant's performance on a startle test?

Researchers will compare healthy volunteers who have taken MDMA to those who have taken placebo.

Participants will first undergo a 1-hour startle test. The next day, they will be randomized to receive either MDMA or placebo followed by another startle test and vitals signs and blood measurements. Participants will return the next day for a final startle test. Their sleep will be tracked by a Fitbit device.

Detailed description: This is a randomized, blinded, placebo-controlled Phase 1 study that aims to evaluate the impact of 3,4-methylenedioxymethamphetamine (MDMA) on startle response.

This study will enroll healthy participants. At Visit 1, all participants will undergo a 1-hour startle test. Acoustic startle will be measured through assessing eye-blink response from the orbicularis oculi muscles in response to a 106 dB noise, using sensors under the eye. While watching the computer monitor, the participant will also experience several brief blasts of air directed at the throat.

At Visit 2 (24 hours later), participants will be randomized to receive 100 mg of MDMA or inactive placebo, after which they will undergo another startle test. Participants enrolled in the study who agree to do this will have their blood drawn to measure levels of oxytocin, and possibly other hormones or proteins, such as cortisol or brain-derived neurotrophic factor (BDNF). Measuring oxytocin will be blind to condition, and the decision will happen before randomization to either condition. Blood will be drawn before MDMA or placebo administration, and eight times afterwards.The researchers will measure pulse, blood pressure and temperature once before and six times after receiving MDMA or placebo, and study participants will complete a questionnaire about their experience.

At Visit 3, participants will return for a final startle test and recall task. Sleep will be measured via self-report and Fitbit during study participation.

Eligibility criteria: Inclusion Criteria:

* Persons aged 21 to 55.
* Ability to visually read and understand English language.
* Live within in metro Atlanta area
* Previously used MDMA in a recreational or research setting
* If a person is of childbearing potential (able to bear children), they must have a negative pregnancy test at study entry and prior to the Experimental Session. They must agree to use adequate birth control through 10 days after the last dose of MDMA. Adequate birth control methods include intrauterine device (IUD), injected or implanted hormonal methods, abstinence, oral hormones plus a barrier contraception or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e. condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom). Not of childbearing potential is defined as permanent sterilization, postmenopausal, or male.
* (For sub-study measuring serum oxytocin) Willing to have periodic blood draws

Exclusion Criteria:

* Upon review of medical or psychiatric history, have any current or past diagnosis that would be considered a risk to participating in the study.
* Are abusing illegal drugs.
* Current use of any psychoactive medications, including antidepressants, mood stabilizers, sedatives, stimulants, antipsychotics, anxiolytics, or beta-blockers
* Are not able to give adequate informed consent.
* Uncontrolled hypertension, or clinically significant cardiac arrhythmia, as detected by electrocardiogram.
* Currently pregnant or breast-feeding.
* History of acute angle glaucoma.
* Hearing impairment as assessed by audiometer; unable to detect tones below 40 dB in right or left ear.

Primary outcomes:
measure: EMG of right orbicularis oculi muscle
timeFrame: Four days post-enrollment
Secondary outcomes:
measure: Systolic blood pressure pre-drug
timeFrame: 5 minutes pre-drug
measure: Systolic blood pressure 45 min post-drug
timeFrame: 45 minutes post-drug
measure: Systolic blood pressure 1 h 15 min post-drug
timeFrame: 1 hour 15 minutes post drug
measure: Systolic blood pressure 1 h 45 min post-drug
timeFrame: 1 hour 45 minutes post drug
measure: Systolic blood pressure 3 h post-drug
timeFrame: 3 hours post-drug
measure: Systolic blood pressure 4 h post-drug
timeFrame: 4 hours post-drug
measure: Systolic blood pressure 5 h post-drug
timeFrame: 5 hours post-drug
measure: Systolic blood pressure 6 h post-drug
timeFrame: 6 hours post-drug
measure: Diastolic blood pressure pre-drug
timeFrame: 5 minutes pre-drug
measure: Diastolic blood pressure 45 min post-drug
timeFrame: 45 minutes post-drug
measure: Diastolic blood pressure 1 h 15 min post-drug
timeFrame: 1 hour 15 minutes post-drug
measure: Diastolic blood pressure 1 h 45 min post-drug
timeFrame: 1 hour 45 minutes post drug
measure: Diastolic blood pressure 3 h post-drug
timeFrame: 3 hours post-drug
measure: Diastolic blood pressure 4 hours post-drug
timeFrame: 4 hours post-drug
measure: Diastolic blood pressure 5 hours post-drug
timeFrame: 5 hours post-drug
measure: Diastolic blood pressure 6 hours post-drug
timeFrame: 6 hours post-drug
measure: Pulse pre-drug
timeFrame: 5 minutes pre-drug
measure: Pulse 45 min post-drug
timeFrame: 45 minutes post-drug
measure: Pulse 1 h 15 min post-drug
timeFrame: 1 hour 15 minutes post-drug
measure: Pulse 1 h 45 min post-drug
timeFrame: 1 hour 45 minutes post-drug
measure: Pulse 3 h post-drug
timeFrame: 3 hours post-drug
measure: Pulse 4 h post-drug
timeFrame: 4 hours post-drug
measure: Pulse 5 h post-drug
timeFrame: 5 hours post-drug
measure: Pulse 6 h post-drug
timeFrame: 6 hours post-drug
measure: Body temperature pre-drug
timeFrame: 5 minutes pre-drug
measure: Body temperature 45 minutes post-drug
timeFrame: 45 minutes post-drug
measure: Body temperature 1 h 15 minutes post-drug
timeFrame: 1 hour 15 minutes post-drug
measure: Body temperature 1 h 45 minutes post-drug
timeFrame: 1 hour 45 minutes post-drug
measure: Body temperature 3 hours post-drug
timeFrame: 3 hours post-drug
measure: Body temperature 4 hours post-drug
timeFrame: 4 hours post-drug
measure: Body temperature 5 hours post-drug
timeFrame: 5 hours post-drug
measure: Body temperature 6 hours post-drug
timeFrame: 6 hours post-drug
measure: Plasma oxytocin (OT) levels predrug
timeFrame: 5 min prior to drug administration
measure: Plasma oxytocin (OT) levels 5 min post-drug
timeFrame: 5 min post-drug administration
measure: Plasma oxytocin (OT) levels 20 min post-drug
timeFrame: 20 min post-drug administration
measure: Plasma oxytocin (OT) levels 95 min post-drug
timeFrame: 95 min post-drug administration
measure: Plasma oxytocin (OT) levels 110 min post-drug
timeFrame: 110 min post-drug administration
measure: Plasma oxytocin (OT) levels 185 min post-drug
timeFrame: 185 min post-drug administration
measure: Plasma oxytocin (OT) levels 200 min post-drug
timeFrame: 200 min post-drug administration
measure: Plasma oxytocin (OT) levels 240 min post-drug
timeFrame: 240 min post-drug administration
measure: Plasma oxytocin (OT) levels 300 min post-drug
timeFrame: 300 min post-drug administration
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Barbara Rothbaum
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maples-Keller JL, Norrholm SD, Burton M, Reiff C, Coghlan C, Jovanovic T, Yasinski C, Jarboe K, Rakofsky J, Rauch S, Dunlop BW, Rothbaum BO. A randomized controlled trial of 3,4-methylenedioxymethamphetamine (MDMA) and fear extinction retention in healthy adults. J Psychopharmacol. 2022 Mar;36(3):368-377. doi: 10.1177/02698811211069124. Epub 2022 Feb 15.