Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Therapy for Treatment of PTSD

PTSD Clinical Trial

Official title:

An Open-Label, Multi-Site Phase 2 Study of the Safety and Effect of Manualized MDMA-Assisted Therapy for the Treatment of Severe Posttraumatic Stress Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03282123
• Other study ID #: MP-16
• Status: Completed
• Phase: Phase 2
• Start date: November 16, 2017
• Est. completion date: August 10, 2019

Study information

• Verified date: January 2024
• Source: Lykos Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multi-site, open-label, Phase 2, lead-in study assesses the safety and effect of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified and trained to work on the sponsor's planned Phase 3 studies will treat at least one open-label participant in this study.

This study will compare the effects of three open-label manualized Experimental Sessions of therapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded by three Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure is the change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) total severity scores from Baseline to Primary Endpoint (Visit 19).

Description:

PTSD is a serious debilitating disorder that negatively impacts a person's daily life. PTSD is a stress-related psychiatric condition that may occur following a traumatic event such as war, disaster, sexual abuse, violence, terrorism, and accidents. PTSD negatively impacts a person's daily life, resulting in relationship difficulties, difficulty in finding and maintaining a job, reduced cognitive and psychosocial functioning, substance abuse, high-cost healthcare use, and increased depression and suicide risk. Available PTSD treatments, including medications and therapy, effectively treat only a fraction of people who try them for adequate dose and duration. People with PTSD can be treated with psychotherapies and pharmacotherapies. In the past decade, there has been a growing amount of research into medications and other methods that may augment the effectiveness of psychotherapy for PTSD

3,4-methylenedioxymethamphetamine is a drug that releases serotonin, norepinephrine and dopamine in the brain and indirectly increases levels of the neurohormones oxytocin, arginine vasopressin and cortisol. The combined neurobiological effects of MDMA increase compassion, reduce defenses and fear of emotional injury, and enhance communication and introspection. MDMA produces anxiolytic and prosocial effects, which counteract avoidance and hyperarousal in the context of therapy. A combined treatment of MDMA and therapy may be especially useful for treating PTSD.

This multi-site, open-label, Phase 2, lead-in study assesses the safety and effect of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified and trained to work on the sponsor's planned Phase 3 studies will treat at least one open-label participant in this study.

This study will compare the effects of three open-label manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded by three Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure is the change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) from Baseline to Primary Endpoint (Visit 19).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: August 10, 2019
• Est. primary completion date: August 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Are at least 18 years old

• Are fluent in speaking and reading the predominantly used or recognized language of the study site

• Agree to have study visits recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions

• Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.

Must agree to inform the investigators within 48 hours of any medical conditions and procedures

• If of childbearing potential, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session.

• Must not participate in any other interventional clinical trials during the duration of the study,

• Must be willing to remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures

• Meet DSM-5 Criteria for Severe PTSD

Exclusion Criteria:

• Are not able to give adequate informed consent

• Have uncontrolled hypertension

• Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] corrected by Bazett's formula)

• Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

• Have evidence or history of significant medical disorders

• Have symptomatic liver disease

• Have history of hyponatremia or hyperthermia

• Weigh less than 48 kilograms (kg)

• Are pregnant or nursing, or are of childbearing potential and are not practicing an effective means of birth control.

• Are abusing illegal drugs

Related Conditions & MeSH terms

• PTSD

Intervention

Drug:
• Midomafetamine
80 to 120 mg MDMA

Behavioral:
• Therapy
Non-directive therapy conducted during MDMA-assisted therapy session

Locations

Country	Name	City	State
United States	Aguazul-Blue Water Inc.	Boulder	Colorado
United States	Trauma Research Foundation	Brookline	Massachusetts
United States	University of Connecticut	Farmington	Connecticut
United States	Wholeness Center	Fort Collins	Colorado
United States	University of Wisconsin at Madison	Madison	Wisconsin
United States	Zen Therapeutic Solutions, LLC	Mount Pleasant	South Carolina
United States	Ray Worthy Psychiatry LLC	New Orleans	Louisiana
United States	Affective Care	New York	New York
United States	New York University	New York	New York
United States	New School Research LLC	North Hollywood	California
United States	San Francisco Insight and Integration Center	San Francisco	California
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Lykos Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores	The Clinician-Administered PTSD Scale for DSM-V (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.	Baseline to 18 weeks post-enrollment
Secondary	Change From Baseline to Visit 19 in Adapted SDS Total Score	The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study to limit missing item-level data as per the FDA requirements and included use of the three-item mean as the total score and imputation of work-related impairment. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score was the mean of the 3 item responses. The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.	Baseline to 18 weeks post-enrollment