This trial is active, not recruiting.

Condition posttraumatic stress disorder
Treatments dexamethasone, placebo (sugar pill)
Sponsor Department of Veterans Affairs
Start date April 2010
End date September 2013
Trial size 102 participants
Trial identifier NCT01090180, 09-052, D6902-R


The purpose of this study is to examine the effects of glucocorticoid administration following traumatic memory reactivation on psychiatric symptoms in veterans with combat-related PTSD, in addition to examining the effects of glucocorticoid administration following traumatic memory reactivation on physiological responses to veteran's personal combat memories. The following hypotheses will be tested:

1. Subjects who receive an exogenous glucocorticoid after traumatic memory reactivation will demonstrate fewer PTSD and depression symptoms one week later, compared to those who receive a placebo after traumatic memory reactivation.

2. The glucocorticoid reduction effects will be cumulative; that is, reduction will persist, and further post-reactivation glucocorticoid administration will further reduce symptoms

3. Decreases in PTSD and depression symptoms will persist at 1, 3, and 6 months for subjects receiving an exogenous glucocorticoid compared to those subjects receiving placebo

4. Subjects who receive an exogenous glucocorticoid after traumatic memory reactivation will demonstrate decreased physiological responses one week later, compared to those who receive a placebo after traumatic memory reactivation.

5. As with the psychological measures, suppression of the physiological measures will demonstrate both persistence over time and accumulation with subsequent post-reactivation glucocorticoid administration.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
Dexamethasone (oral)
anti-inflammatory adrenocortical steroid The following dose schedule will be given: 0.15mg/kg (based on body weight) every 7 days for 4 consecutive weeks
(Placebo Comparator)
Placebo (inactive)
placebo (sugar pill)

Primary Outcomes

Psychophysiological Measures (Skin Conductance, Heart rate, electromyograph of frontalis muscle, electromyograph of corrugator muscle. We expect to see a decrease in all these psychophysiological measures from week to week after each memory activation.
time frame: 7 days after the first administration of study medication, and then 60 minutes after receiving study medication for 3 consecutive weeks

Secondary Outcomes

Clinician Administered PTSD Scale (CAPS). This will be used to measure PTSD symptoms in the past month. It is recognized as the gold standard of PTSD assessment in the field.
time frame: This measure will be administered at the baseline assessment session (before treatment), as well as 1 month, 3 months and 6 months after treatment concludes.
Quick Inventory of Depressive Symptomatology- Self Report (QUIDS-SR). Because depression can be comorbid with PTSD (70% comorbidity found in pilot sample), this assessment will be used to measure depressive symptoms over a 1 week timeframe
time frame: This measure will be administered at all study visits: Baseline, Treatment sessions 1-4, 1 month, 3 months, and 6 months follow up.
PTSD Checklist (PCL). A self-report, face valid measure of PTSD symptoms over a 1 week time period
time frame: This measure will be administered at all study visits: Baseline, Treatment sessions 1-4, 1 month, 3 months, and 6 months follow up.

Eligibility Criteria

Male participants at least 18 years old.

Inclusion Criteria: - male veterans enrolled to receive care through the VA North Texas Healthcare System - diagnosis of combat-related PTSD Exclusion Criteria: - Hypersensitivity to dexamethasone - Current use of steroids - Current psychosis - Organic Brain Damage - Current major depressive disorder with melancholic features - Substance dependence in the last 3 months - Prominent suicidal or homicidal features - Medical conditions: diabetes, uncontrolled hypertension, severe congestive heart failure, hepatic failure, or any other contraindicated medical condition (such as HPA Axis disease, Addison's Disease or Cushing's Disease). - Veterans taking medication with established drug interactions with dexamethasone

Additional Information

Official title Extinction of Fear Memories With Glucocorticoids in Veterans With PTSD
Principal investigator Alina M Suris, PhD
Description Background information and related research: Post-traumatic stress disorder (PTSD) is characterized, among other things, by intrusive memories in the form of unwanted images, nightmares, and flashbacks. These memories are associated with intense distress and involve excessive physiological and psychological responses to fear associated stimuli. Prevalence rates of combat-related PTSD are increasing due to Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) deployments, with the estimated risk for PTSD from service in the Iraq War at 18%, and 11% for Afghanistan. According to the Pentagon's own mental health taskforce, 38% of soldiers, 31% of marines, 49% of National Guard members, and 43% of marine reservists have shown symptoms of post-traumatic stress disorder or other psychological problems within three months of returning from active duty. Estimates from the National Center on PTSD suggest that 40% of OEF/OIF troops may have or will acquire PTSD. The Department of Defense (DoD) reports that 22% of OEF/OIF troops have been flagged for PTSD and referred for follow-up care, and records indicate that over 39,000 OEF/OIF vets had been treated for PTSD as of December, 2006. Current research efforts are exploring the underlying neurochemical changes associated with PTSD. Recently, these efforts have focused on the prevention of PTSD in persons exposed to trauma by administration of medication to affect the underlying neurochemical processes. For example, preliminary evidence suggests that interference with consolidation of trauma-related memories using the beta-antagonist, propranalol, may prevent PTSD in humans with recent traumas. However, given that as much as 90% of the US population is exposed to at least one traumatic event during their lifetime, the utility of this treatment is limited by the logistical problems of treating everyone at risk for developing PTSD after a trauma. To date, there are very few systematic studies on humans that focus on changing the underlying traumatic memory once PTSD has been established. The trauma experience is initially stored in short-term memory, then consolidated into long-term memory. However, the long-term stability conferred by the consolidation process undergoes a period of labiality as follows. Each time a consolidated memory is activated, the memory trace becomes newly labile and must be consolidated again to remain in long-term memory. This process is called reconsolidation. Reconsolidation therefore offers a biologic window during which long-term memories can be disrupted. Preclinical studies have begun to unravel the biological changes that underlie these processes. Both pharmacological agents, including glucocorticoids, and protein synthesis inhibitors can interfere with memory consolidation and reconsolidation. Endogenously produced stress-hormones, or glucocorticoids, enhance consolidation for emotionally-arousing experiences, but these effects are dependent on dose, aversiveness of task, and timing of hormone administration. Conversely, glucocorticoids appear to impair the retrieval of memories of aversive experiences.10 Recent data also suggest that glucocorticoids enhance extinction of traumatic memories. Preclinical work in our laboratory at the UT Southwestern Medical Center has established that corticosterone can dose-dependently reduce an established fear memory in rodents. In this study, mice were trained to associate foot-shock with a specific training context to induce fear memory. When this fear memory was reactivated by the contextual stimulus and then followed by glucocorticoid administration, subsequent reactivation of the fear memory produced significantly less fear responses relative to mice administered saline after memory reactivation. After only one pairing of reactivation and glucocorticoid, this effect was reversible with a subthreshold reminder shock and was transient, indicating that the effect of glucocorticoids was on the extinction process. These results strongly suggested glucocorticoid treatment paired with therapeutic traumatic memory reactivation as a specific therapy for PTSD in humans and directly informed our pilot studies in PTSD patients.
Trial information was received from ClinicalTrials.gov and was last updated in June 2014.
Information provided to ClinicalTrials.gov by Department of Veterans Affairs.