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

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT01188694
• Collaborator: University of Texas (Other), University of Pennsylvania (Other), National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 42
• Locations: 3
• Arms: 3
• Duration (Months): 43
• Patients Per Site: 14
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Posttraumatic Stress Disorder	Drug: Psychotherapy plus Methylene Blue, USP; Behavioral: Psychotherapy plus Placebo; Behavioral: Delayed Psychotherapy	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Enhancing Extinction Learning in Post Traumatic Stress Disorder (PTSD)
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

1. PTSD Symptom Severity-Interview (PSS-I) [Pre-treatment, post-treatment (4 weeks from pre-), 1-month follow-up (from post-), and 3-month follow-ups (from post-)]

   PTSD Symptom Scale - Interview Version, higher scores represent higher PTSD severity (range 0 - 51)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
2	University of Texas	Austin	Texas	United States	78712
3	University of Washington	Seattle	Washington	United States	98195

Sponsors and Collaborators

• University of Washington
• University of Texas
• University of Pennsylvania
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Lori A Zoellner, PhD, University of Washington

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lori Zoellner, Professor, Department of Psychology, University of Washington
• ClinicalTrials.gov Identifier: NCT01188694
• Other Study ID Numbers: 37340; R34MH087375; 107654
• First Posted: Aug 25, 2010
• Last Update Posted: Jun 14, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Methylene Blue

Study Results

Participant Flow

Arm/Group Title	Psychotherapy Plus Methylene Blue, USP	Psychotherapy Plus Placebo	Delayed Psychotherapy
Arm/Group Description	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.	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.	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).
Period Title: Overall Study
STARTED	15	16	11
COMPLETED	10	15	10
NOT COMPLETED	5	1	1

Baseline Characteristics

Arm/Group Title	Psychotherapy Plus Methylene Blue, USP	Psychotherapy Plus Placebo	Delayed Psychotherapy	Total
Arm/Group Description	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.	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.	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).	Total of all reporting groups
Overall Participants	15	16	11	42
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	16 100%	11 100%	42 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	10 66.7%	12 75%	8 72.7%	30 71.4%
Male	5 33.3%	4 25%	3 27.3%	12 28.6%
Region of Enrollment (participants) [Number]
United States	15 100%	16 100%	11 100%	42 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Psychotherapy Plus Methylene Blue, USP	Psychotherapy Plus Placebo	Delayed Psychotherapy
Arm/Group Description	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.	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.	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).
Measure Participants	15	16	11
Pre-Treatment	32.07 (6.17)	31.38 (6.88)	32.73 (7.24)
Post-Treatment	17.10 (10.57)	14.67 (9.27)	29.60 (8.40)
1 Month Follow-up	10.33 (3.77)	13.33 (9.15)	28.33 (7.43)
3 Month Follow-up	7.63 (5.53)	10.93 (9.95)	7.25 (9.82)

Adverse Events

Arm/Group Title	Psychotherapy Plus Methylene Blue, USP		Psychotherapy Plus Placebo		Delayed Psychotherapy
Arm/Group Description	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.		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.		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).
All Cause Mortality
	Psychotherapy Plus Methylene Blue, USP		Psychotherapy Plus Placebo		Delayed Psychotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Psychotherapy Plus Methylene Blue, USP		Psychotherapy Plus Placebo		Delayed Psychotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/16 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Psychotherapy Plus Methylene Blue, USP		Psychotherapy Plus Placebo		Delayed Psychotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/15 (26.7%)		4/16 (25%)		1/11 (9.1%)
Eye disorders
Eye Infection	0/15 (0%)		0/16 (0%)		1/11 (9.1%)
Gastrointestinal disorders
Nausea or Gastrointestinal	4/15 (26.7%)		3/16 (18.8%)		0/11 (0%)
Psychiatric disorders
Anxiety or Depression	1/15 (6.7%)		1/16 (6.3%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.