Neurobiology of Sleep and Sleep Treatment Response in Returning Veterans (NOSSTIP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01637584
Recruitment Status : Completed
First Posted : July 11, 2012
Results First Posted : April 17, 2017
Last Update Posted : May 23, 2017
Information provided by (Responsible Party):
Anne Germain, University of Pittsburgh

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Non PTSD PTSD Drug: Prazosin Drug: Placebo Not Applicable

Detailed Description:
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).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Neurobiology of Sleep and Sleep Treatment Response in Returning Veterans
Study Start Date : April 2010
Actual Primary Completion Date : November 2012
Actual Study Completion Date : November 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Prazosin
Active medication arm. Prazosin is an FDA approved medication, originally designed as an anti-hypertension medication. Side effects of the medication in some include sleepiness and once asleep, sustained sleep.
Drug: Prazosin
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 Comparator: Placebo
A placebo is a sugar pill, which will be used to compare with the results of the active medication
Drug: Placebo
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 Outcome Measures :
  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 Outcome Measures :
  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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01637584

United States, Pennsylvania
Western Psychiatric Institute and Clinic
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Anne Germain, Associate Professor, University of Pittsburgh Identifier: NCT01637584     History of Changes
Other Study ID Numbers: PRO08050307
First Posted: July 11, 2012    Key Record Dates
Results First Posted: April 17, 2017
Last Update Posted: May 23, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
Antihypertensive Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs