Quetiapine Augmentation for Treatment-resistant PTSD

NCT00292370 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: CLIN-006-04F
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to compare the response of veterans with PTSD without an optimal response to paroxetine to quetiapine augmentation versus placebo.

Conditions

Combat Disorders; Stress Disorders, Post-Traumatic

Keywords

Atypical Antipsychotics; Controlled Trial; Paroxetine; Quetiapine; Stress Disorders, Post-Traumatic; Treatment refractory; Treatment resistant

Outcome Measures

Primary Outcomes (1)

• Change in Clinician-Administered PTSD Scale for DSM-IV Total Score.

  The Clinician-Administered PTSD Scale for DSM-IV (CAPS) is described in the National Center for PTSD Instruction Manual (November 2000) as a semi-structured clinical interview designed to assess the seventeen symptoms for Post Traumatic Stress Disorder (PTSD) outlined in the DSM-IV, along with five associated features. Ratings are made on a 5 point continuum from the lowest frequency or intensity to the highest. Total CAPS score is a summed score that ranges from 0 to 136 where 0 is asymptomatic and higher scores equal more severe PTSD symptomatology. Also, a change in total CAPS score of 15 points was proposed as clinically significant change.

  From baseline (week 8) to endpoint (week 16 or termination)

Secondary Outcomes (8)

• Change in CGI-I

  From Baseline (week 8) to Endpoint (week 16 or termination)

• Change in Mean PANSS Total and Subscores From Baseline to Endpoint

  Baseline (week 8) to Endpoint (week 16 or termination)

• Change in Total Mean Hamilton Rating Scale for Depression (HAMD) Scores

  From Baseline (week 8) to Endpoint (week 16 or Termination)

• Change in Total Mean Davidson Trauma Scale (DTS)

  From Baseline (week 8) to Endpoint (week 16 or Termination)

• Change in Mean Q-LES-Q Score From Baseline to Endpoint.

  From Baseline (week 8) to Endpoint (week 16 or termination)

Study Arms (3)

Arm 1: Open Label (OL) Paroxetine

OTHER

Open-label Paroxetine In Phase I, eligible participants will take open-label (OL) Paroxetine (up to 60 mg) daily for 8 weeks. Participants who are refractory (less than 30% reduction in CAPS scores or a minimum CAPS of 50 at week 8) and have PTSD symptoms of at least moderate severity on CGI-S will be eligible for Phase II.

Drug: Open Label (OL) Paroxetine

Arm 2 OL Paroxetine + DB Placebo

PLACEBO COMPARATOR

In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion.

Drug: Open Label (OL) Paroxetine; Drug: Placebo

Arm 3: OL Paroxetine + DB Quetiapine

EXPERIMENTAL

In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion.

Drug: Open Label (OL) Paroxetine; Drug: Quetiapine

Interventions

Open Label (OL) Paroxetine DRUG

Open-label Paroxetine

Also known as: Paxil

Arm 1: Open Label (OL) Paroxetine; Arm 2 OL Paroxetine + DB Placebo; Arm 3: OL Paroxetine + DB Quetiapine

Placebo DRUG

Double-blind placebo taken with OL paroxetine

Also known as: sugar pill

Arm 2 OL Paroxetine + DB Placebo

Quetiapine DRUG

Double-blind quetiapine taken with OL paroxetine

Also known as: Seroquel

Arm 3: OL Paroxetine + DB Quetiapine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veteran age 18 to 75.
• Competent to give informed consent.
• Meeting DSM-IV criteria for PTSD.
• Minimal CAPS score of 50 at baseline.
• If female of childbearing potential, patient must have a negative pregnancy test and, if sexually active, be using a medically approved contraceptive method.
• Patients who have not taken psychiatric medications within 1 week prior to study entry (except fluoxetine \[5 weeks\])
• monoamine oxidase inhibitors (MAOIs \[4 weeks\])
• depot neuroleptics \[4 weeks\])
• or any investigational drug within 30 days prior to study enrollment.
• To be eligible for Phase II
• patients must be refractory to paroxetine in Phase I, as defined by less than 30% reduction in CAPS scores or a minimum CAPS score of 50 at week 8
• must have PTSD symptoms at least moderate severity on CGI-S
• and must have been compliant with study medicine in Phase I, as defined by taking at least 80% of prescribed doses.

You may not qualify if:

• History of sensitivity to paroxetine or quetiapine.
• Failure to respond to a prior adequate therapeutic trial i.e. minimum of 8 weeks at maximum tolerated dose of paroxetine (up to 60 mg daily) or quetiapine (up to 800 mg daily).
• Women who are
• breast-feeding
• pregnant
• expect to become pregnant during the course of the study
• or are sexually active and are not using a medically acceptable method of birth control.
• Presence of clinically significant hepatic
• cardiovascular
• or other medical conditions that may prevent safe administration of paroxetine or quetiapine
• or any other clinically significant unstable medical conditions.

Sponsors & Collaborators

• VA Office of Research and Development: lead
• AstraZeneca: collaborator

Study Sites (3)

Birmingham VA Medical Center

Birmingham, Alabama, 35233, United States

Location

Tuscaloosa VAMC

Tuscaloosa, Alabama, 35404, United States

Location

Ralph H. Johnson

Charleston, South Carolina, 29401-5799, United States

Location

Related Publications (1)

• Weathers FW, Keane TM, Davidson JR. Clinician-administered PTSD scale: a review of the first ten years of research. Depress Anxiety. 2001;13(3):132-56. doi: 10.1002/da.1029.

  PMID: 11387733 BACKGROUND

Related Links

• The National Center for PTSD is part of the US Department of Veterans Affairs

MeSH Terms

Conditions

Combat Disorders; Stress Disorders, Post-Traumatic

Interventions

Paroxetine; Sugars; Quetiapine Fumarate

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates; Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Mark Hamner, MD
• Organization: Ralph H. Johnson VA Medical Center

Mark.Hamner@va.gov

843-789-7799

Study Officials

• Mark B Hamner, MD BS

  Ralph H. Johnson VA Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2006
• First Posted: February 15, 2006
• Study Start: January 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: May 1, 2009
• Last Updated: October 16, 2019
• Results First Posted: July 1, 2014

Record last verified: 2019-09

Locations

US (3)