MDMA-Assisted Psychotherapy for Anxiety Associated With a Life-Threatening Illness

Phase 2

Completed

Conditions: Anxiety

Interventions: Drug: Placebo
Drug: Midomafetamine HCl
Behavioral: Therapy

Registration Number: NCT02427568

Lead Sponsor: Lykos Therapeutics

Brief Summary: The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people with anxiety associated with a life-threatening illness. The main question it aims to answer is: Does anxiety decrease in people receiving two sessions of MDMA-assisted therapy?

Researchers will compare people receiving placebo with therapy to people receiving MDMA-assisted therapy.

* Participants will undergo three non-drug preparatory therapy sessions before their first blinded session of MDMA or placebo with therapy.

* Each medication session will be followed by three non-drug integrative therapy sessions.

* After the second blinded medication session, participants receiving MDMA will complete a third open-label medication session.

* Participants who received placebo will be given the option to crossover and receive three sessions of assisted therapy.

Detailed Description: This Phase 2 pilot study is a randomized, double-blind, placebo-controlled study in 18 participants comparing the effects of MDMA-assisted therapy vs. placebo with therapy. Thirteen participants were randomized to the active dose condition of 125 mg of MDMA HCl (plus an optional supplemental dose of 62.5 mg MDMA HCl) with therapy and five participants were randomized to the placebo with therapy condition. The study consisted of two blinded experimental sessions of MDMA-assisted therapy or placebo with therapy, each session lasting six to eight hours and scheduled two to four weeks apart. Each participant was unblinded one month after their second experimental session in Stage 1. After unblinding, participants receiving MDMA were to complete a third open-label experimental session of MDMA-assisted therapy and participants who originally received placebo had the opportunity to cross over to open-label Stage 2 and receive active MDMA-assisted therapy in 3 sessions.

The primary objective of the study is to assess changes in trait anxiety in subjects receiving active dose MDMA compared to those receiving placebo as measured by State-Trait Anxiety Index (STAI) Trait scores from Baseline to the Primary Endpoint (one month after the second experimental session).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 18

Inclusion Criteria

Diagnosed with life-threatening cancer or non-dementing neurological illness, which can be ongoing or in remission, but with a possibility of recurrence
Prognosis of at least nine months life expectancy from the time of screening
Have anxiety as a result of facing their illness
Are at least 18 years old
Are willing to refrain from taking any psychiatric medications during the study period;
Are willing to commit to medication dosing, experimental sessions, follow-up sessions, and to complete evaluation instruments
Are willing to remain overnight at the study site after each experimental session until after the integrative session occurring the next morning
Must sign a medical release for the investigators to communicate directly with their therapist and doctors;
Are willing to select up to three observers who will complete observer measures of subject attitudes and behavior
Negative pregnancy test if able to bear children and agree to use effective birth control
Are proficient in speaking and reading English
Agree to have all psychotherapy sessions recorded to audio/video.

Exclusion Criteria

Are pregnant or nursing, or if a woman who can have children, those who are not practicing an effective means of birth control;
Weigh less than 48 kg
Are abusing illegal drugs
Are unable to give adequate informed consent
Upon review of past, current drugs/medication must not be on or have taken a medication that is exclusionary
Upon review of medical or psychiatric history must not have any current or past diagnosis that would be considered a risk to participation in the study
Have used "Ecstasy" (material represented as containing MDMA) at least once within twelve months of enrollment.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo with therapy	Placebo	Inactive placebo administered on 2 blinded experimental sessions scheduled 2 to 4 weeks apart. Initial dose possibly followed 1.5 to 2.5 hours later by (optional) inactive placebo supplemental dose.
Placebo with therapy	Therapy	Inactive placebo administered on 2 blinded experimental sessions scheduled 2 to 4 weeks apart. Initial dose possibly followed 1.5 to 2.5 hours later by (optional) inactive placebo supplemental dose.
MDMA-assisted therapy (125 mg)	Midomafetamine HCl	125 mg midomafetamine HCl administered on 2 blinded experimental sessions scheduled 2 to 4 weeks apart. Initial dose possibly followed 1.5 to 2.5 hours later by a (optional) supplemental dose of 62.5 mg.
MDMA-assisted therapy (125 mg)	Therapy	125 mg midomafetamine HCl administered on 2 blinded experimental sessions scheduled 2 to 4 weeks apart. Initial dose possibly followed 1.5 to 2.5 hours later by a (optional) supplemental dose of 62.5 mg.

Primary Outcome Measures

Name	Time	Method
Change in State Trait Anxiety Inventory (STAI) Trait Score From Baseline to Primary Endpoint	Baseline (3 months from enrollment) to Primary Endpoint (one month post-2nd experimental session)	The State-Trait Anxiety Inventory (STAI) is a 20-item self-report measure of intensity of anxiety. Each item consists of a 4-point Likert rating scale ranging from 1 ('Not at all') to 4 ('Very Much So'), with higher scores indicating greater anxiety. Items were summed for a total score that ranged from 20 to 80. The STAI differentiates between State Anxiety, defined as "anxiety experienced in reaction to a specific environmental circumstance," and Trait Anxiety, defined as "long-standing nervous affect or anxiety disorder." The use of the trait subscale as the primary outcome measure was intended to target those anxiety symptoms that are chronic and pervasive.
Primary Endpoint STAI Trait Score	One month post-2nd experimental session	The State-Trait Anxiety Inventory (STAI) is a 20-item self-report measure of intensity of anxiety. Each item consists of a 4-point Likert rating scale ranging from 1 ('Not at all') to 4 ('Very Much So'), with higher scores indicating greater anxiety. Items were summed for a total score that ranged from 20 to 80. The STAI differentiates between State Anxiety, defined as "anxiety experienced in reaction to a specific environmental circumstance," and Trait Anxiety, defined as "long-standing nervous affect or anxiety disorder." The use of the trait subscale as the primary outcome measure is intended to target those anxiety symptoms that are chronic and pervasive.

Secondary Outcome Measures

Name	Time	Method
Change in STAI State Score From Baseline to Primary Endpoint	Baseline (3 months from enrollment) to Primary Endpoint (one month post-2nd experimental session)	The state subscale of the STAI (STAI-S) is a 20-item self-reported scale which assesses subjects' levels of transient, situationally oriented, anxiety. Like the trait subscale, participants respond to each item on the state subscale by selecting a response from a 4-point Likert scale ranging from 4 ("Not at all") to 1 ("Very much so"), with higher scores indicating greater anxiety. Items were summed for a total score that ranged from 20 to 80. The STAI differentiates between State Anxiety, defined as "anxiety experienced in reaction to a specific environmental circumstance," and Trait Anxiety, defined as "long-standing nervous affect or anxiety disorder." The use of the trait subscale as the primary outcome measure is intended to target those anxiety symptoms that are chronic and pervasive.
Change in Beck Depression Inventory-II (BDI-II) Score From Baseline to Primary Endpoint	Baseline (3 months from enrollment) to Primary Endpoint (one month post-2nd experimental session)	The Beck Depression Inventory-II (BDI-II) is a a 21-item self-reported measure of depression according to Diagnostic and Statistical Manual IV (DSM-IV) criteria. Each item is rated on a 4-point Likert scale ranging from 0 to 3. The total score is the sum of 21 items and range from 0 to 63. Score cutoffs indicate: 0-13 minimal depression, 14-19 mild depression, 20-28 moderate depression, and 29-63 severe depression. Higher scores indicate more severe depressive symptoms.
Change in Death Attitudes Profile (DAP) From Baseline to Primary Endpoint	Baseline (3 months from enrollment) to Primary Endpoint (one month post-2nd experimental session)	The Death Attitudes Profile (DAP) is a 32-item self-reported questionnaire that assesses individual attitudes and beliefs about death and dying. Each item on the scale is rated along a 7-point Likert scale ranging from "strongly disagree" (score of 1) to "strongly agree" (score of 7), with higher scores indicating more positive attitudes toward death. The DAP consists of 5 dimensions: fear of death (7 items summed with total scores ranging from 7 to 49), death avoidance (5 items summed with total scores ranging from 5 to 35), neutral acceptance (5 items summed with total scores ranging from 5 to 35), approach acceptance (10 items summed with total scores ranging from 10 to 70), and escape acceptance (5 items summed with total scores ranging from 5 to 35). For each dimension, a mean scale score can be computed by dividing the total scale score by the number of items forming each scale.
Change in Global Assessment of Functioning (GAF) Score From Baseline to Primary Endpoint	Baseline (3 months from enrollment) to Primary Endpoint (one month post 2nd experimental session)	The Global Assessment of Function (GAF) is a measure of a person's global social functioning made through clinical observation. The GAF consists of a single score, with scores ranging from 0 to 100, with 100 reflecting superior function and zero reflecting serious risk of causing harm to the self or others.
Change in MADRS Score From Baseline to Primary Endpoint	Baseline (3 months from enrollment) to Primary Endpoint (one month post-2nd experimental session)	The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item, clinician administered questionnaire used to diagnose the severity of depressive episodes. Each item has a score of 0 to 6. Overall scores are summed and range from 0 to 60. Score cutoffs indicate: 0-6 normal/symptom absent, 7-19 mild depression, 20-34 moderate depression, \> 34 severe depression. Higher scores indicate greater severe depression.
Change in Self-Compassion Scale (SCS) From Baseline to Primary Endpoint	Baseline (3 months from enrollment) to Primary Endpoint (one month post-2nd experimental session)	The Self-Compassion Scale (SCS) is a 26-item self-reported questionnaire that assesses how respondents relate to themselves and treat themselves during difficult or painful experiences. Items are scored along a 5-point Likert-type scale ranging from 1 "almost never" to 5 "almost always." The SCS has six component (subscale) scores: self-kindness, self-judgment, common humanity, isolation, mindfulness, and over-identification. Subscale scores are calculated by computing the mean of subscale item responses. A total self-compassion score is calculated by the sum of the subscale scores and range from 24 to 120 with higher scores indicating greater self compassion. Higher scores have been found to correlate with positive mental health outcomes, as well as decreased depression and anxiety.
Change in Pittsburgh Sleep Quality Inventory (PSQI) From Baseline to Primary Endpoint	Baseline (3 months from enrollment) to Primary Endpoint (one month post-2nd experimental session)	The Pittsburgh Sleep Quality Index (PSQI) is a measure of self-reported sleep quality over a one month period. It consists of 19 items with possible responses ranging from zero to four on a five-point scale. The PSQI consists of seven sub-scales: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleeping medications, and daytime dysfunction. These are all summed to produce a single global scale. Global scores can range from 0 to 21, with higher scores reflecting poorer sleep quality, and a score below 5 indicating good sleep quality.
Change in Posttraumatic Growth Inventory (PTGI) From Baseline to Primary Endpoint	Baseline (3 months from enrollment) to Primary Endpoint (one month post-2nd experimental session)	The Posttraumatic Growth Inventory (PTGI) is a 21-item self-report measure of perceived growth or benefits occurring after a traumatic event. It contains five subscales; relationship to others, new possibilities, personal strength, spiritual change, and appreciation of life. Questions are answered on a scale from 0 (I did not experience this change) to 5 (I experienced this change to a great degree). Items are added to calculate the total PTGI score which ranges from 0 to 105, with higher scores indicative of greater growth.
Change in Functional Assessment of Chronic Illness Therapy Scale (FACIT) From Baseline to Primary Endpoint	Baseline (3 months from enrollment) to Primary Endpoint (one month post-2nd experimental session)	The Functional Assessment of Chronic Illness Therapy Scale (FACIT-Sp) is a 27-item self-report measure of quality of life issues specifically relevant to individuals with a chronic or life-threatening illness or condition. The core questionnaire consists of four subscales: Physical Well-being, Social/Family Well-being, Emotional Well-being, and Functional Well-being. Responses range from 0 (not at all) to 4 (very much), with higher scores indicating greater well-being. For each subscale, total scores were summed and range from 0 to 16.