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Completed

NCT Number: NCT01637584

Neurobiology of Sleep and Sleep Treatment Response in Returning Veterans

The overarching objectives of this study are: 1) To investigate the neurobiology of posttraumatic stress disorder (PTSD) during Rapid Eye Movement (REM) and Non-Rapid Eye Movement (NREM) sleep relative to wakefulness; 2) To identify the neurobiological underpinnings of sleep treatment response to prazosin or placebo during wakefulness, REM sleep, and NREM sleep in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) ( veterans with PTSD; and 3) To explore pre-treatment brain activity patterns during wakefulness, REM sleep, and NREM sleep that predict sleep treatment response. We will also explore the stability of the Positron Emission Tomography (PET) signal by comparing pre- and post-placebo changes in brain glucose metabolism in non-responders. For non-PTSD veterans, the stability of the PET signal will be evaluated in a subsample of 6 veterans without PTSD who will repeat the PET imaging procedures 8 weeks after the initial PET series.

The overarching hypothesis is that PTSD is characterized by neurobiological alterations in the amygdala, medial prefrontal cortex (mPFC), and brain centers involved in the regulation of NREM and REM sleep, and that these neurobiological changes are normalized with effective sleep treatment.

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Key information

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Western Psychiatric Institute and Clinic

Pittsburgh, Pennsylvania, 15213, United States

About this study

PTSD affects both daytime functioning and sleep. Complaints of poor sleep, objective disruption of sleep, and heightened sympathovagal tone during sleep occurring early after trauma exposure increase the risk of developing PTSD up to one year later. (1-4). Insomnia is one the most common reasons for referral to mental health services in active duty personnel (5). In military personnel returning from Iraq and Afghanistan, more than 70 percent of those with PTSD report sleep problems and fatigue, whereas more than 25% percent of those without PTSD endorse these symptoms (6). Other disruptive nocturnal behaviors and sleep disorders including sleep terrors, nocturnal anxiety attacks, simple and complex motor behaviors and vocalizations, acting out dreams, sleep apnea, and periodic leg movement disorders are also frequently reported by PTSD patients (7-12). In PTSD, sleep disturbances independently contribute to poor clinical outcomes such as increased severity of daytime PTSD symptoms (8), depression (13), suicidality (13), general psychiatric distress (14), poorer quality of life and functioning (14), poorer perceived physical health (14), and increased substance use (15;16).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • OIF/OEF veteran
  • Between the ages of 18 and 50 years old
  • Not taking medications known to affect sleep or wake function for 2 weeks

Additional selection criteria for PTSD subjects are:

  • Trauma occurred three months or more before study entry
  • Meeting diagnostic criteria for current PTSD according to the Clinician Administered PTSD Scale (CAPS)
  • Participants will remain in ongoing counseling services

Additional selection criterion for non-PTSD healthy subjects:

  • Not meet DSM-IV diagnostic criteria for current PTSD
  • Have a total score < 13 on the Beck Depression Inventory
  • Participants who are active-duty military personnel will be required to obtain permission from their commander to participate in this study.

Exclusion criteria

  • Current diagnosis of untreated, severe depression as determined by the Structured Clinical Interview for Diagnostic and Statistical Manual- IV Edition (DSM-IV), non-patient version
  • Beck Depression Inventory > 30
  • History of psychotic or bipolar disorder
  • Current history (within 3 months) of substance or alcohol abuse
  • Significant or unstable acute or chronic medical conditions
  • Other current sleep disorders
  • Presence of implanted devices or metal in body such as cardiac pacemaker, aneurysm clip, ear implant, shrapnel, neurostimulators or other metal devices
  • Fear of closed spaces
  • Previous radiation exposure (past year) that exceeds recommended safety limits
  • Pregnancy or breast feeding
  • Resting blood pressure < 90/60 at the screening physical examination
  • Heart rate > 100 beats/minutes
  • Current use of a beta-blocker
  • Use of an alpha-1 antagonist agent in the previous 3 weeks
  • Refusal to follow the safety measures in the case of use of a phosphodiesterase 5 inhibitor (Cialis, Viagra, Levitra)
  • Unexpected, untreated, or serious EKG findings

Treatment and study plan

Prazosin

Drug

The medication will be administered in the same manner, regardless of active or placebo, as the study physician and investigators, as well as the participants, will be blind to the type of medication they are taking.

Placebo

Drug

The medication will be administered in the same manner, regardless of active or placebo, as the study physician and investigators, as well as the participants, will be blind to the type of medication they are taking.

Primary outcomes

  1. Whole Brain Relative Regional Cerebral Metabolic Rate of Glucose

    Time frame: Baseline and post-intervention at 8-10 weeks

    The reported Z value reflect the magnitude of the state difference (Wake vs. Non-REM or Wake vs. REM) within the prazosin group pre-to-post treatment, and after using a mask to adjust for the spurious effects of the passage of time.

Secondary outcomes

  1. Pittsburgh Sleep Quality Index (PSQI):

    Time frame: Baseline and post-treatment at 8-10 weeks

    Self-report sleep quality measure. Scores range from 0 to 21, with higher scores reflecting poorer sleep quality.

Sponsors and collaborators

Lead sponsor

University of Pittsburgh

Other

Registry information

Acronym: NOSSTIP

Important dates

Study start
2010
Primary completion
2012
Study completion
2012
First posted
Jul 11, 2012
Registry last updated
May 23, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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