Enhancing Extinction Learning in Post Traumatic Stress Disorder (PTSD) (HELP)

Posttraumatic stress disorder (PTSD) is a condition that involves intense memories of a traumatic event and intense, persistent feelings of anxiety. There are several effective therapies for PTSD, but they are often time consuming. The investigators want to see if the investigators can shorten treatment time while keeping therapy effective by adding a medication called methylene blue, USP, taken orally as a pill, to the therapy. The specific aims are: 1) To see whether medication plus psychotherapy improves PTSD symptoms more than placebo plus psychotherapy or a waitlist; 2) To examine the long-term outcome of those receiving medication plus psychotherapy 1 and 3 months after treatment has ended; 3) To examine whether medication plus psychotherapy helps with depression, trauma-related cognitions, and functioning.

Study Overview

• Status: Completed
• Conditions: Chronic Posttraumatic Stress Disorder
• Intervention / Treatment: Drug: Psychotherapy plus Methylene Blue, USP; Behavioral: Psychotherapy plus Placebo; Behavioral: Delayed Psychotherapy

Detailed Description

The psychotherapy the investigators are offering in this study is a type of cognitive behavioral therapy called imaginal exposure. In imaginal exposure, the investigators encourage the client to approach the memory of the trauma by recounting the trauma story to the therapist and discussing his or her reactions to the memory.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Austin, Texas, United States, 78712
      • University of Texas
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Current primary PTSD diagnosis based on DSM-IV criteria, with a minimum duration of 12 weeks since the traumatic event.
2. Between the age of 18 and 65.

Exclusion Criteria:

1. Current diagnosis of schizophrenia, delusional disorder, or organic mental disorder as defined by the DSM-IV.
2. Current diagnosis of bipolar disorder, depression with psychotic features, or depression severe enough to require immediate psychiatric treatment (i.e., serious suicide risk with intent and plan).
3. Current diagnosis of alcohol or substance dependence within the 3 previous months.
4. Unwilling or unable to discontinue current trauma-focused psychotherapy or psychotropic medication (at least 1 month medication free).
5. Ongoing intimate relationship with the perpetrator (in assault-related PTSD cases).
6. Unstable cardiovascular, autoimmune, endocrine, neurological, renal, hepatic, retinal, gastrointestinal, or hematological disorder or current seizure disorder.
7. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception for the duration of active treatment.
8. A history of hypersensitivity or allergy to MB.
9. Any condition possibly affecting drug absorption (e.g., gastrectomy).
10. Glucose-6-phosphate dehydrogenase deficiency.
11. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that, in the judgment of the Medical Directors, would make the participant inappropriate for entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psychotherapy plus Methylene Blue, USP	Drug: Psychotherapy plus Methylene Blue, USP; This treatment involves daily visits with a therapist for 50 to 60 minutes for a total of six sessions. At the end of each session, 260 mg of methylene blue, USP will be given.
Placebo Comparator: Psychotherapy Plus Placebo	Behavioral: Psychotherapy plus Placebo; This treatment involves daily visits with a therapist for 50 to 60 minutes for a total of six sessions. At the end of each session, capsules containing the placebo will be given.
Other: Delayed Psychotherapy	Behavioral: Delayed Psychotherapy; Individuals must wait approximately five to six weeks to start treatment. They will come in for two check-in appointments before starting treatment. Treatment will consist of ten twice-weekly psychotherapy sessions (90-120 min each session).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PTSD Symptom Severity-Interview (PSS-I)	PTSD Symptom Scale - Interview Version, higher scores represent higher PTSD severity (range 0 - 51)	Pre-treatment, post-treatment (4 weeks from pre-), 1-month follow-up (from post-), and 3-month follow-ups (from post-)

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of Mental Health (NIMH); University of Pennsylvania; University of Texas

Publications and helpful links

General Publications

• Zoellner LA, Telch M, Foa EB, Farach FJ, McLean CP, Gallop R, Bluett EJ, Cobb A, Gonzalez-Lima F. Enhancing Extinction Learning in Posttraumatic Stress Disorder With Brief Daily Imaginal Exposure and Methylene Blue: A Randomized Controlled Trial. J Clin Psychiatry. 2017 Jul;78(7):e782-e789. doi: 10.4088/JCP.16m10936.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: July 20, 2010
• First Submitted That Met QC Criteria: August 24, 2010
• First Posted (Estimate): August 25, 2010

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Methylene Blue
• Other Study ID Numbers: 37340; 107654 (Other Identifier: FDA IND#); R34MH087375 (U.S. NIH Grant/Contract)