Modafinil in the Treatment of PTSD (Posttraumatic Stress Disorder)

A Double-Blind, Placebo-Controlled Trial of Modafinil in OEF/OIF Combat Veterans With PTSD

The purpose of this study is to determine if modafinil is more effective than placebo in the treatment of posttraumatic stress disorder (PTSD) in male combat veterans who have been deployed to Iraq or Afghanistan.

Study Overview

• Status: Unknown
• Conditions: Posttraumatic Stress Disorder
• Intervention / Treatment: Drug: Modafinil

Detailed Description

There is a high rate of posttraumatic stress disorder (PTSD) in soldiers exposed to combat in Operations Enduring Freedom and Iraqi Freedom (OEF/OIF). Unfortunately, currently available treatments for combat-related PTSD have produced modest treatment gains at best. New treatment strategies that can be directed toward objectively measured correlates of PTSD are urgently needed.

Specific Aims: 1) To determine if there is evidence for the effectiveness and tolerability of adjunctive modafinil in the treatment of combat-related PTSD. We hypothesize that OEF/OIF veterans with PTSD randomized to modafinil 100mg/day for four weeks will experience more improvement in PTSD symptoms than OEF/OIF veterans with PTSD randomized to placebo treatment for four weeks. 2) To determine if PTSD symptom severity is associated with electrophysiological and neuropsychological measures of pre-attention and attention and if these measures change to a greater degree in participants randomized to modafinil versus those randomized to placebo. We hypothesize modafinil treatment will result in greater changes in electrophysiological and neuropsychological measures of pre-attention and attention than placebo treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Tim A Kimbrell, MD; Phone Number: 501-257-1084; Email: timothy.kimbrell@va.gov
• Study Contact Backup: Name: Jeffry M Pyne, MD; Phone Number: 501-257-1983; Email: jeffrey.pyne@va.gov

Study Locations

• United States
  • Arkansas
    • North Little Rock, Arkansas, United States, 72114
      • Recruiting
      • CAVHS Eugene Towbin VA Medical Center
      • Contact: Susan M Jegley, LMSW; Phone Number: 501-257-1731; Email: susan.jegley@va.gov
      • Principal Investigator: Tim A Kimbrell, MD
      • Sub-Investigator: Jeffrey M Pyne, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• OEF/OIF Veteran with a history of deploying to Afghanistan or Iraq
• right-handed
• male 20-60 years of age
• meets Diagnostic and Statistical Manual (DSM-IV) diagnostic criteria for PTSD
• competent to give informed consent
• access to a telephone
• stable psychotropic medication regimen for a minimum of four weeks prior to enrollment
• able and willing to complete the required schedule of evaluations (Baseline in person, 1 week by phone, 2 week in person, 4 week in person)

Exclusion Criteria:

• diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder
• current substance abuse or dependence
• history of seizure disorder or severe traumatic brain injury
• history of attempted suicide within the previous two years or active suicidal ideation within the past month
• currently taking benzodiazepines except for bedtime dosing only
• currently taking stimulant medication
• known allergic reaction to modafinil or currently taking medication
• that may have altered metabolism if taken with modafinil: Tricyclic antidepressants (amitriptyline; nortriptyline; desipramine; imipramine; CNS stimulants (amphetamine; d-ampthetamine; atomoxetine); Carbamazepine; Phenytoin; Phenobarbitol; Rifampin; Ketaconazole; MAO Inhibitors (isoniazid; selegiline); Warfarin; Diazepam; Mephenytoin; Cyclosporine; Theophylline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: modafinil; Study participants randomized to the active arm of the study will take modafinil 100mg capsules orally each day for 4 weeks.	Drug: Modafinil; we will compare the effect of modafinil and matching placebo on clinical and objective measures detailed above.; Other Names: Provigil
Placebo Comparator: Sugar Pill; Study participants randomized to the placebo arm of the study will take matching capsules orally each day for 4 weeks.	Drug: Modafinil; we will compare the effect of modafinil and matching placebo on clinical and objective measures detailed above.; Other Names: Provigil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician Administered PTSD Scale (CAPS)	The CAPS is the gold standard measure of PTSD symptoms	Change in CAPS from baseline to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eye-gaze tracking to facial stimuli	a measure of attentional bias	change in eye-gaze tracking from baseline to 4 weeks
Modified Stroop	a measure of attentional bias	Change in Modified Stroop from baseline to 4 weeks
event related potentials	P50 potential a measure of level of arousal or pre-attentional processing at 3 interstimulus intervals-ISIs	Change in P50 from baseline to 4 weeks

Collaborators and Investigators

• Sponsor: Biomedical Research Foundation
• Collaborators: National Institute of General Medical Sciences (NIGMS); National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Tim A Kimbrell, MD, Central Arkansas VA Healthcare system

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Anticipated): May 1, 2013
• Study Completion (Anticipated): May 1, 2014

Study Registration Dates

• First Submitted: August 3, 2012
• First Submitted That Met QC Criteria: November 9, 2012
• First Posted (Estimate): November 14, 2012

Study Record Updates

• Last Update Posted (Estimate): November 14, 2012
• Last Update Submitted That Met QC Criteria: November 9, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Modafinil; Attentional Bias; p50
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: CAVHS209470-1; 5P20RR020146-09 (U.S. NIH Grant/Contract); 8P20GM103425-09 (U.S. NIH Grant/Contract)