Neurobiology of Sleep and Sleep Treatment Response in Returning Veterans

NCT01637584 | Completed Results DMC

• 1 other identifier: PRO08050307
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Non PTSD; PTSD

Outcome Measures

Primary Outcomes (1)

• Whole Brain Relative Regional Cerebral Metabolic Rate of Glucose

  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.

  Baseline and post-intervention at 8-10 weeks

Secondary Outcomes (1)

• Pittsburgh Sleep Quality Index (PSQI):

  Baseline and post-treatment at 8-10 weeks

Study Arms (2)

Prazosin

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

A placebo is a sugar pill, which will be used to compare with the results of the active medication

Drug: Placebo

Interventions

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.

Prazosin

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

Western Psychiatric Institute and Clinic

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Stocker RP, Cieply MA, Paul B, Khan H, Henry L, Kontos AP, Germain A. Combat-related blast exposure and traumatic brain injury influence brain glucose metabolism during REM sleep in military veterans. Neuroimage. 2014 Oct 1;99:207-14. doi: 10.1016/j.neuroimage.2014.05.067. Epub 2014 Jun 2.

  PMID: 24893322 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Prazosin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Anne Germain
• Organization: UPittsburgh

germax@upmc.edu

4123832150

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 15, 2012
• First Posted: July 11, 2012
• Study Start: April 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: May 23, 2017
• Results First Posted: April 17, 2017

Record last verified: 2017-03

Locations

US (1)