Efficacy of Sleep Interventions for Posttraumatic Stress Disorder (PTSD)

NCT00393874 | Completed Results DMC

• 2 other identifiers: PR054093W81XWH-06-1-0257
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to evaluate and compare the effects of experimental treatments aimed at improving insomnia and nightmares in men and women military veterans between the ages of 18 and 60 years old, and who have a condition called Posttraumatic Stress Disorder. Insomnia refers to difficulty falling or staying asleep, although enough time is allowed for sleeping. Insomnia is also associated with daytime consequences, such as lack of energy, irritability, and difficulty concentrating. Nightmares are bad dreams that may or may not awaken the sleeper, and that cause discomfort during the daytime. Chronic Posttraumatic Stress Disorder (PTSD) refers to symptoms that occur after someone experienced or witnessed a life-threatening event, and that persist for three months or more after the event. Symptoms include flashbacks, nightmares, feelings of detachment from others, sleep disturbances, irritability, anxiety, and efforts to avoid people and places associated with the life-threatening event. These symptoms occur after a life-threatening event. Symptoms that persist for more than one month indicate the presence of PTSD. In the present study, we will study people with chronic PTSD, which refers to PTSD symptoms that persist for more than 3 months. Efficacy of a treatment is defined as the capacity to produce the desired effects. In this study, we will evaluate and compare the capacity of two active experimental treatments to reduce insomnia and nightmares associated with PTSD, and one inactive intervention, called a placebo, for people who continue to have sleep difficulties despite receiving treatment with an antidepressant medication called a selective serotonin reuptake inhibitor (SSRI, like Prozac, Paxil, Zoloft, Celexa). The two active experimental treatments are a medication, prazosin, and a brief behavioral intervention, which involves exercises and techniques to reduce nightmares and improve sleep quality. Prazosin is an approved medication by the Food and Drug Administration (FDA) against high blood pressure, but is not FDA-approved for posttraumatic insomnia and nightmares.

Conditions

Anxiety Disorders; Mood Disorders; Insomnia; Nightmares

Keywords

Anxiety D/O; Mood D/O

Outcome Measures

Primary Outcomes (4)

• Insomnia Severity Index

  Self-report measures of insomnia severity. Scores range from 0 to 28, with higher scores indicated more severe insomnia. A score \< 8 is considered to reflect no significant insomnia.

  Screening, Post, and Follow-up

• Sleep Diary Measures

  Sleep diary SE, nightmare frequency Sleep diary sleep efficiency can range from 0 to 100%, and typically varies between 50% and 95%. Higher % values reflect greater sleep consolidation, i.e., greater ratio of time asleep/time in bed. Nightmare frequency varies between 0 and no upper limit is provided. Greater frequency of nightmares reflects greater nightmare severity.

  baseline and post

• PSG Composite Measure

  Sleep Efficiency (SE) is the ratio of total time spent asleep over total time spent in bed. For PSG studies, (SE) typically vary between 50% and 95%. Greater values indicated more consolidated sleep.

  Baseline sleep study and post sleep study

• PSQI

  Self-report sleep quality measure. Scores range between 0 and 21, with higher scores reflecting poor sleep quality. A score of \< or = to 5 reflects good sleep quality.

  Baseline, post, 4 months post-treatment

Study Arms (3)

Medication

ACTIVE COMPARATOR

Treatment will be conducted under double blind conditions and will last a total of 8 weeks. Participants will also receive printed educational material about sleep hygiene developed by the American Academy of Sleep Medicine. Items include going to bed when drowsy, avoiding clock watching while awake in bed, avoidance of caffeine and alcohol, engaging in moderate exercise, and ensuring comfortable sleep environment. Clinical ratings will be obtained weekly throughout the trial.Medications will be administered in a single dose to be taken 30 minutes prior to bedtime because the onset of action occurs within 30 to 90 minutes after a single dose. The research pharmacy will prepare each dose in identical gelatin capsules to prevent identification.

Drug: Prazosin

Behavioral

ACTIVE COMPARATOR

Participants randomized to BSI will receive the intervention aimed at reducing nightmares, insomnia, and sleep avoidance behavior. The treatment will be administered over 8 weeks. The intervention sessions will consist of two individual, 45-minute treatment sessions, delivered on Weeks 1 and 3. A 45-minute "booster" session will be conducted on Week 5. Thirty-minute face-to-face contacts will be scheduled on other weeks (i.e., Weeks 2, 4, 6, 7 and 8) to address any difficulty with the treatment instructions and techniques, to answer questions that may have occurred, and to complete weekly clinical ratings (CGI-I/SR and ASES).

Behavioral: Behavioral Sleep Intervention

Placebo

PLACEBO COMPARATOR

Participants randomized to PLA will take 4 capsules each night, and capsule will be identical to prazosin capsules. As for participants randomly assigned to PRZ, they will receive a one-week medication supplies in daily dose dispensers. Similarly, participants will also be instructed to be ready for bed at the time they take the medication, and not to engage in any activities that will prevent them from going to bed. A placebo pill condition is included for several reasons. First, there is no approved treatment approach currently recognized as being effective for sleep disturbances associated with combat-related PTSD, and which is being withheld from subjects assigned to the placebo arm of the study. We will monitor subjects carefully and on a weekly basis.

Drug: Placebo

Interventions

Behavioral Sleep Intervention BEHAVIORAL

Participants will receive a workbook with information related to the intervention. The three core components are presented and discussed during these sessions are:1) education about sleep and nightmares; 2) imagery rehearsal; 3) stimulus control and sleep restriction. Session 1 focuses on education on PDSD-related insomnia, nightmares, and sleep avoidance behaviors. The rationale for imagery rehearsal will then be presented, and the technique will be practiced once. Strategies for managing intrusive thoughts and images during the practice of imagery rehearsal will be discussed. Participants will be instructed to practice this technique at least three times each day for the duration of the treatment phase. During the second 45-minute session (Week 3), sleep schedules extracted from the pre-intervention sleep diary will be used to identify goals to reduce insomnia, i.e., for sleep restricted schedules, and activities to be performed out of bed when awake.

Also known as: Behavioral Intervention for Insomnia and Nightmares

Behavioral

Prazosin DRUG

Participants randomized to PRZ will take 4 capsules each night (PRZ dose complemented with placebo capsules ). The target dose of prazosin is 10 mg. Some individuals may require doses up to 15 mg, (Murray Raskind, M.D., personal communication, February 4, 2005). Prazosin will be administered in an initial oral dose of 1 mg (Week 1), with titration to a maximum of 15 mg. The first increment will be of 1 mg (Week 2: 2 mg), and subsequent weekly increments according to the following schedule: Week 3: 4 mg; Week 4: 6 mg; Week 5: 10 mg; Week 6: 15 mg; Week 7: 15 mg; Week 8: 15 mg. A maximum dose of 15 mg may be necessary. Medication will be administered in a single dose to be taken 30 minutes prior to bedtime because the onset of action occurs within 30 to 90 minutes after a single dose.

Also known as: MINIPRESS®, Vasoflex®, Hypovase®,

Medication

Placebo DRUG

Participants randomized to PLA will take 4 capsules each night for eight weeks, all capsules will be identical to prazosin capsules. As for participants randomly assigned to PRZ, they will receive a one-week medication supplies in daily dose dispensers. Similarly, participants will also be instructed to be ready for bed at the time they take the medication, and not to engage in any activities that will prevent them from going to bed.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Military veterans
• Age between 18 and 55 years old
• Reports of insomnia and nightmares
• Current diagnosis of PTSD
• Currently treated with an SSRI.
• Medications and dosages will remain unchanged for the duration of the study
• Participants will agree to remain in ongoing counseling services they may be receiving prior to study entry.
• Able to read and write English
• Provision of written informed consent

You may not qualify if:

• Current, severe, untreated Major Depressive Disorder
• Current history of suicidality requiring hospitalization
• Current history (past 6 months) of substance or alcohol abuse
• Currently actively psychotic or bipolar disorder (past year)
• Resting blood pressure \< 90/60 at the screening physical examination
• Heart rate \> 100 beats/minutes
• Use of an alpha-1 antagonist agent or beta-blocker
• Refusal to follow the safety measures
• Unexpected, untreated, or serious EKG findings
• Medications and/or dosage changed in the past two months
• Unstable medical condition
• Pregnant or breast-feeding women
• Apnea-hypopnea index (AHI) \> 15
• Refusal to provide information relevant to selection criteria

Sponsors & Collaborators

• University of Pittsburgh: lead
• U.S. Army Medical Research and Development Command: collaborator

Study Sites (1)

Western Phychiatric Institute and Clinic, University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Germain A, Richardson R, Moul DE, Mammen O, Haas G, Forman SD, Rode N, Begley A, Nofzinger EA. Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US Military Veterans. J Psychosom Res. 2012 Feb;72(2):89-96. doi: 10.1016/j.jpsychores.2011.11.010. Epub 2011 Dec 20.

  PMID: 22281448 DERIVED

MeSH Terms

Conditions

Anxiety Disorders; Mood Disorders; Sleep Initiation and Maintenance Disorders

Interventions

Behavior Therapy; Prazosin; Sugars

Condition Hierarchy (Ancestors)

Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbohydrates

Results Point of Contact

• Title: Dr. Anne Germain
• Organization: University of Pittsburgh

GERMAX@upmc.edu

412-383-2150

Study Officials

• Anne Germain, Ph.D.

  Department of Psychiatry University of Pittsburgh School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: October 26, 2006
• First Posted: October 30, 2006
• Study Start: October 1, 2006
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2011
• Last Updated: October 24, 2016
• Results First Posted: October 24, 2016

Record last verified: 2016-09

Locations

US (1)