The Effects of MDMA on Prefrontal and Amygdala Activation in PTSD.

NCT03752918 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 2000020348
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the effects of MDMA on prefrontal and amygdala activation, and to explore the relationship between these MDMA-induced neural changes and the acute behavioral effects of the drug in patients with PTSD.

Conditions

Post Traumatic Stress Disorder

Keywords

MDMA

Outcome Measures

Primary Outcomes (1)

• Changes in activation of mPFC, amygdala, and nucleus accumbens upon presentation of emotional faces.

  This will be assessed using mixed effects regression models, with group, time, and group X time effects modeled to examine the effect of MDMA on region of interests (ROI) activation. We will also assess the functional connectivity of between these ROIs.

  Initial Drug Dose, 2 weeks post drug dose (second drug dose).

Secondary Outcomes (17)

• Changes in PTSD symptoms, which will be measured by The Clinician-Administered PTSD Scale 5 (CAPS-5).

  Baseline, Initial Drug Dose and Second Drug Dose, 24 hours and 1 week after initial and second drug dose.

• Changes in depression symptoms, which will be measured by The Beck Depression Inventory II (BDI-II).

  Baseline, Initial Drug Does and Second Drug Dose, 24 hours after initial and second drug dose, 3 and 5 days after initial and second drug dose (by phone), 1 week after initial and second drug dose, 15, 17, 19, and 21 days after second drug dose (phone).

• Changes in sleep patterns, which will be measured by The Pittsburgh Sleep Quality Index (PSQI).

  Baseline, 24 hours after first and second drug dose, 1 week after initial and second drug dose.

• Changes in PTSD symptoms, which will be measured by The Posttraumatic Stress Disorder Checklist for the DSM-5 (PCL-5).

  Baseline, 24 hours after initial and second drug dose, 3 and 5 days after initial and second drug dose (phone), 1 week after initial and second drug dose, 15, 17, 19, and 21 days after second drug dose (phone).

• Changes in personality traits, which will be measured by The NEO Personality Inventory - Revised (NEO PI-R).

  Baseline, 1 week after initial and second drug dose.

Study Arms (2)

MDMA

EXPERIMENTAL

MDMA (1.5mg/kg)

Drug: MDMA

Niacin

PLACEBO COMPARATOR

Niacin (250mg)

Drug: Niacin

Interventions

MDMA DRUG

A single dose of 1.5mg/kg will be administered once orally.

Also known as: 3,4-Methylenedioxymethamphetamine

MDMA

Niacin DRUG

A single dose of 250mg will be administered once orally.

Also known as: Nicotinic acid

Niacin

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females between the ages of 21-55 years. Females will be included if they are not pregnant and agreed to utilize a medically (non-hormonal)\* accepted birth control method (to include implant birth control, condom, diaphragm with spermicide, intrauterine device, tubal ligation, abstinence, or partner with vasectomy) or if post-menopausal for at least 1 year, or surgically sterile.
• Able to provide written informed consent according to Yale HIC guidelines.
• Able to read and write English as a primary language.
• Diagnosis of PTSD, as determined by the Clinician Administered PTSD Scale (CAPS-5).
• Must have a score of 23 or higher on the Clinician-Administered PTSD Scale (CAPS-5) at screening.
• No more than mild TBI according to a modified version of the Brief TBI Screen.
• Must not have a medical/neurological problem or use medication that would render MDMA unsafe by history or medical evaluation.
• No prior exposure to MDMA.
• Are willing to remain overnight at the study site after each experimental session.
• Are willing to be driven home the day after the experimental sessions.
• Not currently taking any of the listed medications at the time of the study.
• Are willing to sign a medical release for the investigators to communicate directly with their therapist and doctors.
• Are willing to abstain from alcohol, street drugs, and tobacco products while in the study.

You may not qualify if:

• Patients with a diagnostic history of bipolar disorder, schizophrenia or schizoaffective disorder or currently exhibiting psychotic features as determined by the MINI 7.0 for the DSM-5.
• Serious suicide or homicide risk, as assessed by evaluating clinician.
• Substance abuse or dependence during the 6 months prior to screening; or a positive pre-study (screening) urine drug screen.
• Any significant history of serious medical or neurological illness.
• Any signs of major medical or neurological illness on examination or as a result of ECG screening or laboratory tests (e.g. positive urine tox, positive HIV/AIDS tests ).
• Abnormality on physical examination. A participant with a clinical abnormality may be included only if the study physician considers the abnormality will not introduce additional risk factors and will not interfere with the study procedure.
• Pregnant or lactating women or a positive urine pregnancy test for women of child-bearing potential at screening or prior to any imaging day.
• Any history indicating learning disability, mental retardation, or attention deficit disorder.
• Family history of cardiovascular diseases. History of hypertension with baseline blood pressure above 140 mmHg (systolic) and over 90 mmHg (diastolic). Any history of syncope and/or baseline blood pressure below 100mmHg (systolic).
• History of claustrophobia.
• BMI \> 30 kg/m2 or \>250 pounds.
• Anxiolytic, neuroleptic and SRI medications (off SRIs for 4 weeks, fluoxetine 5 weeks).
• Any metal or electromagnetic implants, including: (Cardiac pacemaker, artificial heart valve, defibrillator, aneurysm clip, cochlear implants, shrapnel, neurostimulators, history of metal fragments in eyes or skin, significant hearing loss or other severe sensory impairment, a history of seizures or current use of anticonvulsants.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

Location

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MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

N-Methyl-3,4-methylenedioxyamphetamine; Niacin

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Benjamin Kelmendi, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Research Scientist

Model Details: This study will be a double-blind, placebo-controlled, within-subjects, crossover-dose neuroimaging study in which participants will initially receive either a single dose of MDMA 1.5mg/kg or a placebo (niacin 250mg), with a crossover dose to follow. Doses will be separated by 2 weeks.

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: November 26, 2018
• Study Start: May 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 17, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)