Atomoxetine in Veterans With Comorbid ADHD/PTSD

• ClinicalTrials.gov Identifier: NCT02287038
• Recruitment Status: Completed
• First Posted: November 10, 2014
• Results First Posted: April 3, 2019
• Last Update Posted: April 3, 2019
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

Brief Summary:

The current available treatments for PTSD are not fully effective for cognitive symptoms of PTSD and have high drop-out and poor engagement, two factors found to be most indicative of overall return to functioning for patients with PTSD. The proposed study directly addresses this knowledge gap by conducting a pilot, fixed-dose, randomized, double-blind, placebo-controlled, and cross-over trial using atomoxetine (ATX) as an add-on medication to other therapies to testing the efficacy of ATX in reducing ADHD cognitive symptoms among veterans with comorbid ADHD/PTSD. Successful completion of this pilot clinical trial may build a platform for future large scale double-blind, placebo-controlled studies using either atomoxetine or other cognitive enhancing medications.

Condition or disease	Intervention/treatment	Phase
Post Traumatic Stress Disorder; Attention Deficit Hyperactivity Disorder	Drug: Atomoxetine 80 MG	Phase 4

Detailed Description:

Combat Veterans with posttraumatic stress disorder (PTSD) often show cognitive impairments in attention, working memory, executive functions, and inhibitory control, a cluster of symptoms resembling symptoms of ADHD. The presence of comorbid ADHD cognitive symptoms is often associated with greater PTSD clinical severity and poorer treatment outcomes. While treatments for the avoidance, arousal, and re-experiencing symptoms associated with PTSD for military personnel are readily available, substantial gaps exist in the treatment of the cognitive deficits associated with PTSD. As a result, untreated co-occurring ADHD cognitive symptoms in PTSD may have severe negative impacts on patients' functional recovery, treatment outcome, and quality of life. The proposed study directly addresses this knowledge gap by testing the feasibility and preliminary efficacy of atomoxetine (ATX) in treatment of ADHD cognitive symptoms among those with comorbid ADHD/PTSD. This is a small prospective, 10-week, fixed-dose, randomized, double-blind, placebo-controlled, and cross-over trial of ATX as an add-on medication to other therapies in Veterans with comorbid ADHD/PTSD. Primary outcome measures will be ADHD cognitive symptom reduction and quality of life improvement as measured by the Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S) and the Adult ADHD Quality of Life-29 (AAQoL-29). Secondary outcome measures will be PTSD and depressive symptoms reduction as measured by the Clinician Administered PTSD Scale (CAPS), the Hamilton Depression Scale (HAM-D). In addition to subjective measures, the response inhibition task Go/NoGo (GNG) will be used as objective assessments to measure ATX treatment outcomes. The proposed work is innovative; it applies novel therapeutic agent to treat cognitive symptoms in PTSD. To our knowledge, this is the first study to apply a SNRI to address an often overlooked PTSD-cognitive deficit. This study is directly responsive to the mission of RR&D-SPiRE "to maximize functional recovery" of cognitive function in PTSD. The outcome of the proposed research will be significant, because it provides a knowledge base to help determine who is at risk for developing treatment resistance among PTSD patients, thereby allowing for development of early intervention strategies. More importantly, this clinical trial may immediate benefit Veterans by enhancing their cognitive function, reducing ADHD symptoms related disability, and further improving quality of life for veterans suffer from comorbid ADHD/PTSD.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: A small prospective, 10-week, fixed-dose, randomized, double-blind, placebo-controlled, and cross-over trial of atomoxetine as an add-on medication to other therapies in Veterans with comorbid ADHD/PTSD.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: randomized, double-blind, placebo-controlled, and cross-over trial
• Primary Purpose: Treatment
• Official Title: Atomoxetine in Comorbid ADHD/PTSD: A Pilot, Placebo-Controlled Feasibility Study
• Actual Study Start Date: October 15, 2014
• Actual Primary Completion Date: March 2, 2017
• Actual Study Completion Date: April 14, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Atomoxetine 80mg; Atomoxetine (fixed dose of 80mg), a non-stimulant medication, FDA approve for treatment of ADHD. The active drug will be applied in first phase in group one and in second phase in group two	Drug: Atomoxetine 80 MG; Subjects will be randomized and assigned by the study investigator into crossover group 1 (Atomoxetine 80mg at Phase I, then placebo at Phase II) or group 2 (placebo at Phase I, then Atomoxetine at Phase II) with both placebo and medication administered through pharmacy. There was a 1-week interval between the two phases.; Other Name: Strattera
Placebo Comparator: Placebo; A pharmaceutically inert substance, which will be given to group one in their second phase and group tow in first phase.	Drug: Atomoxetine 80 MG; Subjects will be randomized and assigned by the study investigator into crossover group 1 (Atomoxetine 80mg at Phase I, then placebo at Phase II) or group 2 (placebo at Phase I, then Atomoxetine at Phase II) with both placebo and medication administered through pharmacy. There was a 1-week interval between the two phases.; Other Name: Strattera

Outcome Measures

Primary Outcome Measures :

1. Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S, Conner et al, 1999) [ Time Frame: Visit 1, (Day1), Visit 4(Day 36), Visit 7 (Day 71) ]
   Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S, Conner et al, 1999): The CAARS-S:S is a 26-item questionnaire that assesses symptoms of ADHD in persons aged 18 years or older. T-scores above 65 indicate a likelihood of moderate to severe ADHD symptoms and impairment. The range for the CAARS-S:S is from 0 to 78. A score of 78 would resemble the worst symptoms of ADHD with a score 0 having no symptoms.
2. The Adult ADHD Quality of Life-29 (AAQOL-29, Brod et al, 2006) [ Time Frame: Visit 1 (Day1), 4(Day 36), 7 (Day 71) ]
   The Adult ADHD Quality of Life-29 (AAQOL-29, Brod et al, 2006): AAQoL-29 is a 29-item questionnaire designed to assess quality of life and was a secondary efficacy measure in this trial. It is a participant-reported outcome measure used to examine disease specific functional impairments and quality of life for adults with ADHD. The AAQoL is scored as an overall total score, measuring Life Productivity, Psycholofical Health, Relationship, and Life Outlook. Each item is rated by patients on a 5-point Likert scale ranging from "Not at all/Never" (1) to "Extremely/Very Often" (5). To derive overall scores, item scores are transformed to a 0-100-point scale (1=0; 2=25; 3=50; 4=75; 5=100). Then, the item scores are summed up and divided by item count to generate overall scores. The score range from 0 to 100. A higher score indicates greater QoL and better functioning.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Veterans age 20 to 60 with PTSD and significant ADHD symptoms (CAARS-S:S > 65);
• Good physical health.

• Evidence of combat as defined by:

  • Trauma exposure sufficient to meet Category A of PTSD criteria (Breslau and Kessler 2001)

Exclusion Criteria:

• Age younger than 20 or greater than 60.
• Known sensitivity to ATX
• Presence of disorders that could conceivable be exacerbated by atomoxetine (specifically, narrow angle closure glaucoma, urinary outflow obstruction, hypertension, and neurological disorders, particularly tics and Tourette's syndrome, or a history of epilepsy or seizures).
• Use of concomitant medication that could potentially interact with atomoxetine including monoamine oxidase inhibitors (MAOI), antihypertensive medication, or any concomitant medication that was a cytochrome 2D6 inhibitor (CYP2D6), since atomoxetine's elimination involves the CYP2D6 system.
• An active or lifetime major mental health diagnosis as determined by DSM-IV Axis I Disorders, including schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified, bipolar I disorder, bipolar II disorder, bipolar disorder not otherwise specified. The project will allow presence of depressive disorders if the depressive episodes are secondary to PTSD.
• Current substance dependence and abuse (within 3 month).
• Females who are pregnant.
• Suicidal thoughts and behavior. b. Sources of Material

Contacts and Locations

Locations

United States, South Carolina

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, United States, 29401-5799

Sponsors and Collaborators

VA Office of Research and Development

Investigators

• Principal Investigator: Zhewu Wang, MD; Ralph H. Johnson VA Medical Center, Charleston, SC

  Study Documents (Full-Text)

Documents provided by VA Office of Research and Development:

Study Protocol and Statistical Analysis Plan  [PDF] August 25, 2016

More Information

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02287038
• Other Study ID Numbers: D1725-P; I01BX007080 ( Other Grant/Funding Number: VA Office of Research and Development )
• First Posted: November 10, 2014
• Results First Posted: April 3, 2019
• Last Update Posted: April 3, 2019
• Last Verified: March 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:

PTSD; ADHD; Atomoxetine; Combat Trauma; Cognitive Deficit

Additional relevant MeSH terms:

Disease; Stress Disorders, Traumatic; Attention Deficit Disorder with Hyperactivity; Stress Disorders, Post-Traumatic; Pathologic Processes; Trauma and Stressor Related Disorders; Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Atomoxetine Hydrochloride; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Adrenergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs