## Protocol Section
### Identification Module
**NCT ID:** NCT06418178

**Acronym:** DosOp

**Brief Title:** Dose Optimization of MDMA-Assisted Therapy for PTSD

**Official Title:** A Dose Optimization Study of MDMA-Assisted Therapy for PTSD in U.S. Veterans

#### Organization Study ID Info
**ID:** 171633
#### Organization
**Class:** FED
**Full Name:** Bronx VA Medical Center
### Status Module
#### Completion Date
**Date:** 2029-10

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2029-10

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-10

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-06
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** FED

**Name:** Bronx VA Medical Center

#### Responsible Party

**Investigator Affiliation:** Bronx VA Medical Center

**Investigator Full Name:** Rachel Yehuda

**Investigator Title:** Mental Health Patient Care Center Director

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This open label, within-subjects dose optimization trial will investigate the optimal number of MDMA-Assisted Therapy treatment cycles (i.e., one MDMA session and three integration sessions) in a sample of U.S. veterans with PTSD. Participants will complete from one to five cycles of MDMA-AT.

**Detailed Description:** This open label, within-subjects dose optimization study will determine the optimal number of treatment cycles of MDMA-AT (one cycle consists of one Experimental Session followed by three Integrative Sessions) for significant improvement in a sample of U.S. veterans with PTSD. All participants will receive three non-drug preparatory sessions and at least one cycle of MDMA-assisted therapy with a team of two therapists. Each cycle will consist of one approximately 8-hour drug session followed by three 90-minute non-drug integrative sessions. After each cycle, participants will determine, in consultation with their therapy team, whether to continue with an additional cycle or to discontinue treatment. The decision will reflect the participant's perception of the potential for continued improvement (e.g., as based on current symptom burden, treatment response to date) weighed against the burden of an additional cycle (e.g., time required, any adverse events or emotional burden). Participants may complete up to a maximum of five cycles. The dose optimizing design allows for the identification of the optimal number of MDMA-AT cycles to achieve the best response and to assess tolerability of multiple cycles of MDMA-AT. Participants will also provide blood samples to be banked for future analysis of biological markers associated with treatment response.

For each participant, the study will consist of:

* Screening Period: initial screen, informed consent, eligibility assessment
* Enrollment Period with Enrollment Confirmation: Enrollment and medication tapering period (if needed) followed by psychological assessment and Enrollment Confirmation, collection of biomarker blood samples.
* Treatment Period: 3 Preparatory sessions; one to five Experimental Sessions, each followed by 3 non-drug Integrative Sessions and a follow-up visit with study therapists
* Post-treatment Period and Study Termination: Psychological Evaluation, biomarker blood samples, study termination visit

### Conditions Module

**Conditions:**

- Posttraumatic Stress Disorder

**Keywords:**

- Posttraumatic Stress Disorder

- MDMA-Assisted Therapy

- Dose Optimization

- Veterans

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Open label, within-subjects treatment arm. Participants receive 120mg + optional 60mg supplement. There will be from one to five dosing sessions that occur three to five weeks apart. Each dosing session is followed by three integration psychotherapy sessions.

**Intervention Names:**

- Drug: Midomafetamine

- Behavioral: Psychotherapy

**Label:** Treatment Arm

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Treatment Arm

**Description:** One to five MDMA-assisted therapy sessions, each followed by three non-drug psychotherapy sessions (see behavioral intervention below)

**Name:** Midomafetamine

**Other Names:**

- MDMA

- 3,4-methylenedioxymethamphetamine

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Treatment Arm

**Description:** Standardized psychotherapy performed by therapy team

**Name:** Psychotherapy

**Type:** BEHAVIORAL

### Outcomes Module

#### Primary Outcomes

**Description:** The PCL-5 is a 20-item self-report questionnaire in which respondents indicate the presence and severity of PTSD symptoms per DSM-5. Participants indicate how much distress they have experienced due to each symptom on a five-point Likert-type scale (1=Not at all to 5=Extremely).

**Measure:** PTSD Checklist for DSM-5 (PCL-5)

**Time Frame:** From Baseline to Outcome Site Visit (up to ~27 weeks for participants who complete all five treatment cycles)

#### Secondary Outcomes

**Description:** The last month CAPS-5 is a semi-structured interview that assesses index history of DSM-5-defined traumatic event exposure and past-month symptom severity to produce a diagnostic score (presence vs. absence) and a PTSD Total Severity score. The CAPS-5 rates intrusion symptoms (intrusive thoughts or memories), avoidance, cognitive and mood symptoms, arousal and reactivity symptoms, duration and degree of distress and dissociation.

**Measure:** Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

**Time Frame:** From Pre-treatment Psychological Evaluation to Post-treatment Psychological Evaluation (up to ~28 weeks for participants who complete all five treatment cycles)

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Are a U.S. military veteran at least 18 years old.
2. Are able to provide written, informed consent.
3. Are able to swallow pills.
4. Agree to have study visits recorded, including Experimental Sessions, psychological assessments, and non-drug therapy sessions.
5. Must provide a contact who is willing and able to be reached by the investigators in the event of a participant becoming unwell or unreachable.
6. If able to become pregnant, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate contraceptive methods.
7. Must have a current PTSD diagnosis at screening and baseline.
8. Must not participate in any other interventional clinical trials for the duration of the study.
9. Must commit to medication dosing, therapy, and all study procedures.

Exclusion Criteria:

1. Are not able to give adequate informed consent.
2. Have a history of any medical condition, or any significant clinical finding on screening tests, that could make receiving a sympathomimetic drug harmful.
3. Have uncontrolled hypertension.
4. Have evidence or history of significant medical or psychiatric disorders.
5. Have symptomatic liver disease.
6. Have history of hyponatremia or hyperthermia.
7. Weigh less than 48 kilograms (kg).
8. Unable or unwilling to safely taper off prohibited psychiatric medication.
9. Abusing illegal drugs or alcohol.
10. Have received Electroconvulsive Therapy (ECT) or ketamine therapy within 12 weeks of enrollment.
11. Are pregnant or nursing or are able to become pregnant and are not practicing an effective means of contraception.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Amy.Lehrner@va.gov

**Name:** Amy Lehrner, PhD

**Phone:** 718-584-9000

**Phone Ext:** 3205

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** James J. Peters VA Medical Center

**Name:** Rachel Yehuda, PhD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** James J. Peters VA Medical Center

**Name:** Amy Lehrner, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000068099

- Term: Trauma and Stressor Related Disorders

- ID: D000001523

- Term: Mental Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

- Abbrev: BC26

- Name: Wounds and Injuries

### Condition Browse Module - Browse Leaves

- ID: M24916

- Name: Stress Disorders, Traumatic

- Relevance: HIGH

- As Found: Stress Disorder

- ID: M16103

- Name: Stress Disorders, Post-Traumatic

- Relevance: HIGH

- As Found: Posttraumatic Stress Disorder

- ID: M17685

- Name: Wounds and Injuries

- Relevance: LOW

- As Found: Unknown

- ID: M222

- Name: Trauma and Stressor Related Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000040921

- Term: Stress Disorders, Traumatic

- ID: D000013313

- Term: Stress Disorders, Post-Traumatic

### Intervention Browse Module - Ancestors

- ID: D000006213

- Term: Hallucinogens

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000011619

- Term: Psychotropic Drugs

- ID: D000018490

- Term: Serotonin Agents

- ID: D000018377

- Term: Neurotransmitter Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000018759

- Term: Adrenergic Uptake Inhibitors

- ID: D000014179

- Term: Neurotransmitter Uptake Inhibitors

- ID: D000049990

- Term: Membrane Transport Modulators

- ID: D000018663

- Term: Adrenergic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: PsychDr

- Name: Psychotropic Drugs

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M20876

- Name: N-Methyl-3,4-methylenedioxyamphetamine

- Relevance: HIGH

- As Found: Crossover Trial

- ID: M17835

- Name: 3,4-Methylenedioxyamphetamine

- Relevance: LOW

- As Found: Unknown

- ID: M9305

- Name: Hallucinogens

- Relevance: LOW

- As Found: Unknown

- ID: M14474

- Name: Psychotropic Drugs

- Relevance: LOW

- As Found: Unknown

- ID: M15512

- Name: Serotonin

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20746

- Name: Adrenergic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000018817

- Term: N-Methyl-3,4-methylenedioxyamphetamine

### Misc Info Module

- Version Holder: 2024-05-31
