Predictors of Treatment Response to Fluoxetine in PTSD Following a Recent History of War Zone Stress Exposure

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by TEMPVA Research Group, Inc..
Recruitment status was  Recruiting
Sponsor:
Collaborators:
C.R.Darnall Army Medical Center
Central Texas Veterans Health Care System
VA Boston Healthcare System
Information provided by:
TEMPVA Research Group, Inc.
ClinicalTrials.gov Identifier:
NCT00633685
First received: March 4, 2008
Last updated: May 24, 2010
Last verified: February 2010
  Purpose

Three hundred (300) male or female outpatients, over 18 years of age, will be enrolled in this study to determine whether fluoxetine can be used as a treatment for Posttraumatic Stress Disorder in soldiers recently returning from combat exposure. There will be two phases to the study. In Phase I Fluoxetine + usual psychological care will be compared with Placebo + usual psychological care over a 12-week period. Subsequently, in Phase II all subjects will be offered the opportunity to enroll in a 20-week open-label trial on Fluoxetine. If response is inadequate, adjunctive treatment with either buspirone or bupropion will be offered. The investigational drugs are Fluoxetine, Buspirone and Bupropion. All are commercially available.


Condition Intervention Phase
Posttraumatic Stress Disorder, Combat-related
Drug: Fluoxetine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Predictors of Treatment Response to Fluoxetine in PTSD Following a Recent History of War Zone Stress Exposure

Resource links provided by NLM:


Further study details as provided by TEMPVA Research Group, Inc.:

Primary Outcome Measures:
  • Clinician Administered PTSD Scale [ Time Frame: 12-Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PTSD Symptom Checklist [ Time Frame: Every follow-up encounter (weeks 2-32) ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: March 2010
Estimated Study Completion Date: August 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fluoxetine
Receives Fluoxetine at 20-60 mg daily for 12 weeks in a flexible dosage schedule based upon clinical response
Drug: Fluoxetine
Fluoxetine will be administered at 20-60 mg daily for 12 weeks in a flexible dosage schedule based upon clinical response
Other Name: Prozac
Drug: Placebo
Placebo will be empty gelatin capsules that are identical in size and shape to active treatment
Other Name: Gelatin capsule
Placebo Comparator: Placebo Drug: Fluoxetine
Fluoxetine will be administered at 20-60 mg daily for 12 weeks in a flexible dosage schedule based upon clinical response
Other Name: Prozac
Drug: Placebo
Placebo will be empty gelatin capsules that are identical in size and shape to active treatment
Other Name: Gelatin capsule

Detailed Description:

While most soldiers exposed to the stresses of the war-zone exhibit psychological resilience, about one-fifth become psychological casualties of war. The fact that such a significant number of soldiers have difficulty adapting to life after war exposure suggests that we need to have well-defined treatments that are effective and cost-efficient. Currently, recommendations for first-line pharmacological management of Post-Traumatic Stress Disorder focus on the use of selective serotonin re-uptake inhibitors (SSRIs) such as fluoxetine. Despite this recommendation by the DoD/VA Clinical Practice Guidelines, there have not been any studies evaluating the effectiveness of these medications in patients that have recently been exposure to war-zone stressors. In fact, studies in Vietnam Era veterans have shown limited effectiveness of SSRIs for PTSD. In addition, there is very limited information available to understand the factors that influence whether a particular soldier will respond to treatment with an SSRI. This study is designed to determine whether fluoxetine is an effective treatment for PTSD and associated conditions in soldiers with recent war-zone exposure, as well as determine whether response to SSRIs is related to the severity of the trauma exposure and PTSD symptoms, psychological resilience, adequacy of social supports (family, extra-military and military), post-deployment stressors and life adversity, or the degree of any cognitive impairment.

After informed consent is given, fluoxetine (150 subjects) or placebo (150 subjects) will be administered for 12 weeks in doses from 20 mg daily up to 60 mg daily to active duty soldiers who are already receiving usual psychological care in the Resilience and Restoration Center of the Carl R. Darnall Army Medical Center at Ft. Hood. At the conclusion of this initial phase of the study, all participants will receive fluoxetine in doses up to 80 mg daily for an additional 20 weeks. All participants will be regularly monitored to determine changes in their PTSD symptoms. If a subject does not have at least a 50% improvement after being given 80 mg daily of fluoxetine for 4 weeks, then they will be randomly assigned to also receive either bupropion SR (150 mg daily) or buspirone (up to 40 mg daily) in an attempt to amplify the response to fluoxetine. Statistical analyses will be used to determine which factors provided the greatest influence on the response to these medication trials.

Each subject will be asked to receive a physical exam, give medical history information, and receive a diagnostic interview prior to participation in the study. After being randomly assigned to treatment, subjects will have interview or questionnaire assessments at weeks 2, 4, 6, 8, 12, 16, 20, 24, 28 and 32. Based solely on the degree of response as measured by the PTSD Checklist (a questionnaire that will be administered at each study visit), the dosage of study medication fluoxetine or placebo capsules will be adjusted by a pre-determined schedule.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Veteran of the OEF/OIF war campaigns with violence exposure sufficient to qualify for a diagnosis of PTSD
  2. DSM-IV diagnosis of Post-Traumatic Stress Disorder as determined by the CAPS.
  3. Entry Total CAPS score of at least 65
  4. No exposure to psychotropic medications except for zolpidem for at least two weeks (five weeks for fluoxetine) prior to the baseline assessments.
  5. If female, a negative beta-human chorionic gonadotropin pregnancy test and willing to use oral contraceptives

Exclusion Criteria:

  1. History of intolerance to fluoxetine
  2. History of lack of responsivity to a 60 mg daily dose of fluoxetine
  3. Current or past history of Bipolar Disorder or Schizophrenia
  4. Diagnosis of Major Depressive Disorder, Obsessive-Compulsive Disorder, or Other Anxiety Disorder, unless PTSD is the principal focus of treatment and the onset of PTSD preceded that of the concurrent disorders
  5. Significant history of suicidal or homicidal behavior/ideation
  6. Substance dependence in the past 6 months
  7. Serious general medical condition that would risk the patient being able to complete the pharmacological trial with fluoxetine
  8. Concomitant use of other antidepressants, antipsychotics or mood stabilizers
  9. If female, pregnancy or unwilling to use oral contraceptives
  10. Participation in another research drug trial within 30-days of enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00633685

Contacts
Contact: Paul B Hicks, M.D., Ph.D. 254-743-2643 paul.hicks@va.gov

Locations
United States, Texas
Carl R. Darnall Army Medical Center Recruiting
Ft. Hood, Texas, United States, 76544-4752
Contact: Michael Adams, Ph.D.    254-286-7804    michael.adams@amedd.army.mil   
Principal Investigator: Michael Adams, Ph.D.         
Sponsors and Collaborators
TEMPVA Research Group, Inc.
C.R.Darnall Army Medical Center
Central Texas Veterans Health Care System
VA Boston Healthcare System
Investigators
Principal Investigator: Paul B Hicks, M.D., Ph.D. Central Texas Veterans Health Care System
  More Information

No publications provided

Responsible Party: Paul B. Hicks, M.D., Ph.D./Associate Chief of Staff for Research, Central Texas Veterans Health Care System
ClinicalTrials.gov Identifier: NCT00633685     History of Changes
Other Study ID Numbers: PR064845, PR064845
Study First Received: March 4, 2008
Last Updated: May 24, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by TEMPVA Research Group, Inc.:
Posttraumatic Stress Disorder
Fluoxetine
Factors predicting response
Resilience
Pharmacologic augmentation strategies

Additional relevant MeSH terms:
Fluoxetine
Combat Disorders
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Anxiety Disorders
Mental Disorders
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014